Grapes, particularly red and purple ones, are more than just tasty fruits. They carry an impressive array of potential health benefits, thanks to the high levels of resveratrol they contain. This antioxidant is linked to the prevention of various types of cancer, including breast, liver, and stomach cancer. But the power of grapes and resveratrol extends far beyond this, offering a range of other health and wellness advantages.

Resveratrol is a powerful phytonutrient found in certain plants and fruits, including grapes. It boasts antioxidant and anti-inflammatory effects, contributing significantly to its health benefits. Not only can resveratrol protect the body from oxidative stress and inflammation, but it also aids in the prevention of some types of cancer. Its antioxidant capacities also improve skin appearance, reduce blood cholesterol levels, and promote overall well-being. Although resveratrol can be consumed through supplements, it is also abundant in natural grape juice, red wine, and cocoa. However, it is important to note that excess resveratrol can cause gastrointestinal disorders and that supplements should be used under the guidance of a healthcare professional.

Its not just the fruit of the grape vine that carries health benefits. Grape stems, rich in phenolic compounds, have emerged as a valuable natural ingredient in the cosmetics industry. These compounds have strong antioxidant and anti-inflammatory properties, promoting skin health, combatting signs of aging, and shielding skin from environmental stressors. The antioxidant abilities of these compounds effectively fight free radicals, which can accelerate aging. Moreover, grape stem extracts can soothe irritated skin and reduce redness, offering effective and eco-friendly solutions for skin care.

Resveratrols health benefits extend to the cardiovascular system. This chemical compound is known for its effectiveness in treating cardiovascular diseases, allergies, and obesity. Its anti-obesity properties aid in lowering insulin levels and improving glycemic control. While generally safe, high dosages of resveratrol can lead to gastrointestinal issues. Pregnant women, infants, and people with bleeding disorders should exercise caution.

Among the different types of grapes, red grapes stand out for their health benefits. They contain higher resveratrol content compared to green and black grapes, making them a healthier choice. The resveratrol in red grapes is linked to heart health, antioxidant properties, anti-inflammatory effects, and potential cancer prevention. Incorporating red grapes into daily diets can be an easy and delicious way to boost health.

Polyphenols, a group of naturally occurring antioxidants found in plant-based foods and supplements, are another health benefit of grapes. These compounds have anti-inflammatory benefits and protect against diseases like cancer, cardiovascular diseases, and neurodegenerative diseases. Over 8,000 unique polyphenols are found in foods like fruits, vegetables, teas, wines, olive oil, and spices. Consuming polyphenols can reduce the risk of chronic diseases, improve vascular function, and have anti-cancer effects. They can also reduce oxidative stress and have anti-aging properties. Incorporating polyphenols into your diet can provide many health benefits.

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Health Benefits of Grapes: Unpacking Resveratrol, Skin Health, and Cardiovascular Benefits - Medriva

The skincare ingredient is all over our TikTok feeds but what actually is it and does it really deserve all the attention?

From Argireline and Matrixyl to anti-wrinkle straws and not moving your face at all, TikTok has propagated a range of different anti-ageing hacks over the years, with varying degrees of practicality and effectiveness. Its not surprising that there is so much demand for this kind of advice people are more afraid than ever of showing visible signs of ageing and reactions on social media can verge on cruel if someone is deemed to look too old. We live in a time where however you age, whatever you do, its your fault, as we increasingly view anti-ageing as a personal responsibility. Under this lens, looking older becomes a moral failing, as Laura Pitcher wrote earlier this year.

Amidst this landscape, a new skincare ingredient has been all over our TikTok feeds recently: resveratrol. Here is one of the biggest science-based interventions I used to reverse the ageing in my skin, shares TikTokker Mikayla Flynn before introducing the viewers to resveratrol in a video that has over 1.2 million views. Derived from grapes, berries and nuts, resveratrol is an antioxidant praised for its potential to combat ageing at a cellular level. But does resveratrol really hold the key to everlasting youth, or is it just the latest fleeting obsession in this digital age?

Popularised by Harvard longevity biologist David Sinclair, resveratrol is a polyphenol antioxidant that has been deemed a powerhouse anti-aging ingredient for the whole body. Resveratrol is a phytoalexin derived from the skin of grapes. It contains both antioxidant and anti-inflammatory properties, explains Dr Jaimie Glick MD, dermatologist at New York Dermatology Group.

Resveratrol can be taken as a supplement or applied topically to the skin, but either way it boasts antioxidant, anti-inflammatory and anti-cancer properties. When applied as skincare, the molecular structure of resveratrol enables it to penetrate the skin barrier, where it works to extend the lifespan of cells and bolster collagen production, promoting skin repair while also fortifying the skins natural defences against environmental stressors, including harmful UV rays and pollution.

Resveratrol interacts with the skin on a molecular level by easily penetrating the skin barrier and increasing the lifespan of cells, says Dr Dendy Engelman, a board-certified cosmetic dermatologist and Mohs Surgeon at Shafer Clinic in New York City. It can also stimulate collagen production and protect from UV rays. This translates to slowing the appearance of ageing skin.

Resveratrol has been shown to protect against oxidative stress by acting as a scavenger for free radicals. It also interferes with inflammatory pathways, states Dr Glick. Like all antioxidants, resveratrol protects your cells from accumulating damage. By elevating antioxidant levels in the skin, it expedites the skins healing process, resulting in a smoother complexion. Its protective shield against UV damage and pollution helps stave off premature ageing, preserving skin elasticity and firmness. In addition, the polyphenol has hydrating and soothing properties that offer vitality for tired and stressed skin.

Beyond anecdotal claims on the internet, resveratrols efficacy has been tested in numerous research studies. In addition to its anti-aging properties, resveratrol shows promise in penetrating the skin barrier and in addressing specific skin concerns such as acne and eczema. Its anti-inflammatory properties calm redness, reduce irritation and promote overall skin health. In some clinical studies, resveratrol-containing formulations have shown efficacy in alleviating acne lesions and improving the symptoms of inflammatory skin conditions, assisting with a more rapid healing of wounds on the body.

Its most popular supposed effect is, of course, the power it has to anti-age. It works against the effects of free radicals and oxidative stress, extending the lifespan of skin cells and mitigating DNA damage. A recent study showed nightly application of resveratrol was associated with increased collagen production and a decrease in reactive oxygen species leading to clinical improvement in elasticity and skin thickness, says Dr Glick.

In-vitro studies have shown the benefits of resveratrol for prevention of photoaging and even for acne. In one study, the ingredient showed antibacterial activity for a sustained, longer period of time. Does resveratrol compare to other skincare ingredients like retinol and Vitamin C in terms of its effectiveness? Given resveratrols ability to affect skin from a molecular level, it has astounding capabilities to help diminish fine lines and improve tone and texture. Ingredients like retinol and vitamin C may show more immediate results, but adding resveratrol into your routine will help boost and prolong results, says Dr Engelman.

As with any skincare ingredient, its essential to exercise caution and consult with a dermatologist before integrating something new into your skincare regimen, particularly if you have sensitive skin or specific concerns. But for the most part, its generally safe to use. Because of its anti-inflammatory effects I find it particularly well-tolerated. Products containing resveratrol have even been shown to improve facial redness and rosacea, says Dr Glick.

There are, of course, some studies that show a different side to the miracle ingredient, especially when claiming that we can take resveratrol as a supplement and instantly become ten years younger. At the Johns Hopkins University School of Medicine, scientists conducted a study on about 800 men and women, all who were above the ages of 65 and had diets full of foods that were naturally rich in resveratrol. To their surprise, the participants urine analysis didnt contain any difference in resveratrol levels.

It seems ingesting resveratrol has shown no benefit, except if youre consuming it in high doses. Another 2014 paper on reducing blood pressure concluded that when comparing lower and higher supplementation, participants who took more resveratrol showed decreased hypertension.

Beauty brands are investing in research and development more than, and anti-ageing unsurprisingly remains their top priority. I am sure we will see more start to bubble up with resveratrol. With benefits such as anti-aging, UV protection and anti-inflammatory properties, we can expect to see resveratrol in many more sunscreens and skin care products, says Dr Engelman.

Of course, like with all skincare products, no-one needs to use resveratrol and there is nothing wrong with showing signs of ageing. Getting older is a privilege and the only people who benefit from our insecurities around ageing, ultimately, is beauty corporations and their profit margins.

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Resveratrol: what is TikToks latest anti-ageing skincare obsession? - Dazed

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The manufacturers of Glucotrust ensure that they integrate the best natural ingredients to craft this unique product for tackling diabetes. The product contains no parabens or preservatives that could deteriorate the health condition in the long run. All the benefits derived from the product come from natural sources. Let us take a glance at them;

Gymnema Sylvestre: Gymnema Sylvestre is the main component in numerous sugar-controlling pills. The rich content of antioxidants in the natural ingredient ensures that no inflammation or injury can be sustained. Consequently, the rich content of vitamins, minerals, and amino acids cannot be ignored as they increase the ingredient's potency by manifolds.

Biotin Vitamin B7: Biotin Vitamin B7 plays a crucial role in the absorption of natural glucose into the bloodstream and converting the same for energy. It also stimulates the stem cells to produce beta cells, aggravating insulin production and diverting complications.

Chromium: Chromium nullifies all the complications and deficiencies related to diabetes. In addition, it propels better sugar absorption and usage for energy requirements. There is an increased insulin production and enhanced sensitivity that can regulate sugar levels.

Manganese: Numerous medical health experts promote the consumption of manganese for a better nervous system, guided by the aggravated brain's cognitive functioning. It increases the production of leptin in the body, which defers the cravings for fast food or excessive carbohydrates. Such functionality prevents the sugar from getting oxidized into the bloodstream and promotes better sleep for energy recovery.

Licorice Root: Glucotrust shares the inclusion of Licorice root into its manufacture in consonance with its predecessors. Licorice root is an undeniable part of staple Ayurvedic medicine. Not many know that Licorice harbors glycyrrhizin, which inhibits glucose absorption into the bloodstream.

Cinnamon: Also known as the king of spices, Cinnamon promotes better digestion and healthy sugar levels in the body. It stimulates increased insulin production and better glucose metabolism that promotes the overall well-being of a diabetic individual. The presence of antioxidant properties helps tackle issues like inflammation, diseases, and irregular sleep schedules to give a better life.

Zinc: Zinc has a plethora of never-ending benefits. Industry experts feel that there is not one aspect of human health that zinc does not help improve. Three hundred working enzymes in the human body require an adequate supply of zinc for promoting metabolism, reproduction, growth, and immune system functionalities. Besides reducing the sugar levels, it also tackles the triglycerides that keep the cholesterol levels under check.

Juniper Berries: Do you know an evergreen shrub that offers multiple health benefits besides being a natural sugar inhibitor? Juniper berries are a great anti-diabetic ingredient that can reduce sugar cravings by manifolds. Its combination with chromium aids in aggravated fat loss and assists in the diabetic journey.

Glucotrust promotes numerous advantages of its consumption, making it one of the most sought-after products for diabetic patients. Knowing the benefits can convince any individual to give this product a try.

Weight loss

People suffering from obesity or carrying more body weight than recommended are the ones who suffer from ailments like diabetes. Glucotrust aids in reducing sugar consumption and promotes increased metabolism for getting rid of excess weight.

Controlling Appetite

The major reason behind people gaining extra weight is their lack of tongue control. People crave good food that has a lot of spices and carbohydrates to treat their taste buds. However, such food remains detrimental to health and opens the door for numerous ailments. Glucotrust prohibits food cravings and lowers the appetite to a considerable level.

Diabetic Assistance

The main benefit of Glucotrust is to keep diabetes under control. It facilitates better sugar absorption in the human body and converts it into energy required to fulfill the day's responsibilities. The extensive set of ingredients included in Glucotrust's manufacture substantiates the effectiveness concerning its sugar control.

Boosted Immune System

One of the vital benefits of Glucotrust is to offer a better immune system. Ever since the onslaught of COVID-19, people understood the importance of building immunity for sustaining in a world vulnerable to viruses. Glucotrust offers an amalgamation of immunity and weight loss to keep the diabetes level under control. Thus, the benefits are multiple.

Promotes Deep Sleep

Increased sugar levels can mess with the hormonal secretion in the human body. Hormonal disbalance often causes an increase in cortisol levels that puts people under extreme stress. Such a situation deprives them of the necessary sleep to sustain. Glucotrust mitigates cortisol levels and enhances sleep quality.

Is Glucoredi safe?

Yes, Glucoredi is safe for human consumption and remains devoid of side effects.

What is the main benefit of Glucoredi?

Glucoredi helps control type-2 diabetes.

How to consume Glucoredi?

According to the manufacturers, consuming Glucoredi twice a day will give optimal results.

Make your life better with the best resveratrol supplement of your choice! The options mentioned above are the most trusted ones and have passed the necessary tests for approval.

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Best Resveratrol Supplements 2024 - Top Product Brands on the Market - Deccan Herald

One of the main reasons so many of us tend to steer clear of retinol isthat while the popular ingredient may be a holy grail when it comes to reversing signs of aging, not all skin responds well to such a powerful vitamin. Caudalie's newest serum was made with everyone in mind. It'sformulated with resveratrol as a high-performing retinol alternative. "The patented combination of resveratrol, micro hyaluronic acid, and new vegan collagen 1 works synergistically to deliver the best results,"Kwitman tells us.Resveratrol and retinol may work in a similar way, but to an in vitro test on ingredients association, one is much more versatile than the other.

But what is resveratrol? According to Kwitman, it's harnessed from the grapevine stalk and works to increase activity in the anti-aging cells. Made from 98% natural origin ingredients, the Resveratrol-Lift Instant Firming Serum also happens to be vegan, recyclable, and gentle, which makes it an effective alternative for retinol. "The serum is clinically proven to be three times more effective than retinol to firm and lift," she says. "This is critical because by the time you reach 40 years old, you have lost nearly 40% of your collagen and 50% of your hyaluronic acid." In other words, the older you get, the more changes you'll notice to the skin. Using Caudalie's patented resveratrol formula can help pump the breaks.

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The New Addition to Caudalie's Resveratrol-Lift Collection - Who What Wear

Introduction

Endometriosis (EMS), a hormone-dependent gynecological inflammatory disease, is defined as the endometrium, including both stroma and glands, presenting at the extrauterine sites, mostly involving pelvic organs and peritoneum.1 It may also affect external pelvic organs and even the central and peripheral nervous systems.1 Endometriosis affects 10% of women of reproductive age.2 Approximately 3080% of women with this disease experience pelvic pain, and 3040% of women are accompanied by infertility, representing the two major clinical symptoms.3,4 In addition to the aforementioned symptoms and phenomena, endometriosis also has adverse effects on the quality of life, such as sleep quality, physical and psychological well-being, sexual function, and interpersonal relationships, resulting in a large economic burden to individuals, the healthcare system, and society.5,6 Furthermore, some studies have reported that endometriosis is closely correlated with the elevated incidence rate of endometrial and ovarian malignant tumors, which may be implicated as a precursor to epithelial ovarian cancer and may have a tumor-promoting effect on ovarian cancer.7,8

At present, pharmacotherapy and surgical resection are the main therapeutic approaches for endometriosis. Pharmacotherapy mainly consists of hormone therapies that induce hypoestrogenism or antagonize estrogen effects, such as progestines (including the levonorgestrel-releasing intrauterine system (LNG-IUS), dienogest and medroxyprogesterone acetate), combined oral contraceptive pills (COCs), aromatase inhibitors, danazol, gestrinone, gonadotropin-releasing hormone agonist (GnRH-a) and GnRH antagonist (GnRH-ant), selective estrogen/progestogen receptor modulators (SERMs/SPRMs), and nonhormone therapy for alleviating endometriosis-related pain, such as nonsteroidal anti-inflammatory drugs (NSAIDs).9 However, the efficacies of conventional medications are limited or discontinuous in the majority of patients, as long-term usage of these drugs will bring about perimenopausal symptoms, breakthrough bleeding and osteoporosis due to the hypoestrogenic status, as well as other adverse effects such as thrombosis, and liver function damage.10,11 Although surgical management aims to completely destroy or remove visible ectopic lesions, restore normal anatomy, alleviate pain, and ameliorate infertility,12 the recurrence rate and reoperation rate of endometriosis after surgery are relatively high. It has been shown that the incidence of disease relapse is 21.5% within 2 years after surgery, and 4050% within 5 years,13 and the reoperation rate is 2758%.13,14 Surgery combined with hormonal maintenance treatment reduces the risk of disease recurrence,13 but hormonal treatment inhibits follicular development and ovulation, which opposes reproductive requirements in some patients. In recent years, several emerging nonhormonal therapeutic strategies, such as dopamine agonists and bentamapimod, have achieved prospective outcomes and may become complementary treatment options for endometriosis.15

Due to the limitations of existing therapeutic strategies, it is necessary to exploit new supplementary and alternative drugs to improve the treatments of endometriosis. In the past few decades, natural compounds mainly obtained from herbs have been increasingly studied. Natural compounds have potential advantages over synthetic drugs that are developed via target-based assays in terms of tolerance, side effects, and cost-effectiveness, promising to be new therapeutic options for endometriosis. Among them, resveratrol has attracted tremendous attention due to its wide range of biological activities, including anti-neoplastic, anti-oxidant, anti-angiogenic, anti-proliferative, anti-inflammatory, antiglycosylated, antiaging, and pro-apoptotic activities.1621 Resveratrol (3,5,4-trihydroxysilbene) is a natural dietary phytochemical mainly found in beans, peanuts, wine, tea, and some fruits,2225 and it is also found in several microorganisms, such as Botulinum, Penicillium and Cephalosporium.26 Structurally, resveratrol belongs to phenols, existing as cis- or trans-isomers, and it is composed of two aromatic rings linked by an ethylene bridge. Trans-resveratrol can be isomerized into cis-resveratrol when exposed to heat, light, or ultraviolet radiation, of which trans-resveratrol is the major natural form,27,28 and the biological activities of trans-resveratrol are more significant than cis-resveratrol.29,30 Resveratrol has been confirmed to have pleiotropic properties that significantly depend on its structures, including hydroxyl groups, hydrogen bonds and double bonds.31 Some researchers have indicated the possible mechanisms by which resveratrol treats cancers, thereby decreasing the incidence rate and inhibiting the development of diseases. Thus, resveratrol is considered a prospective agent for the treatment of various malignant tumors, such as cervical cancer, breast cancer, liver cancer, pancreatic cancer, colorectal cancer and prostate cancer.17,3235 Other biological activities of resveratrol have also been reported, including cardioprotective, vasorelaxant, phytoestrogenic and neuroprotective activities.3639

Based on the available in vitro, in vivo, and clinical studies as well as the pathology and pathogenesis of endometriosis, this review generalizes the efficacies of resveratrol against endometriosis and its possible molecular mechanisms, highlighting the underlying efficacy of resveratrol in the treatment of endometriosis. This review also provides a comprehensive overview of the theoretical foundation of resveratrol in clinical trials for endometriosis (Figure 1, Table 1).

Table 1 Researches Investigating the Effects and Potential Molecular Mechanisms of Resveratrol Against Endometriosis

Figure 1 Potential molecular mechanisms of resveratrol on endometriosis. This figure was created with MedPeer (www.medpeer.cn).

Abbreviations: , increase; , decrease; Ang-1, angiotensin-1; CAT, catalase; COX-2, Cyclooxygenase-2; ER, estrogen receptor alpha; GLUT, glucose transporters; GSH-Px, glutathione peroxidase; HGF, hepatocyte growth factor; ICAM-1, Intercellular cell adhesion molecule-1; IGF-1, insulin-like growth factor-1; IL, interleukin; INF-, Interferon gamma; M, macrophage; MCP-1, monocyte chemotactic protein 1; MCT, monocarboxylate transporters; MDA, malonyl dialdehyde; MMP, matrix metalloproteinase; MTA1, metastasis-associated protein 1; NK cell, natural killer cell; NO, nitric oxide; PCNA, proliferating cell nuclear antigen; RANTES, regulated upon activation, normal T-cell expressed and secreted; SIRT1, Sirtuin 1; SOD, superoxide dismutase; TGF-, transforming growth factor-beta; TIMP, tissue inhibitors of metalloproteinase; TNF-, tumor necrosis factor-alpha; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling; VEGF, vascular endothelial growth factor; ZEB2, zinc finger E-box binding homeobox 2.

Despite research efforts and extensive investigations, the unequivocal etiologies and pathogenesis of endometriosis remain elusive. Currently, several hypotheses have been proposed for endometriosis to illustrate the pathological mechanism as follows: retrograde menstruation, lymphatic and hematogenous dissemination, peritoneal metaplasia, activation of Mullerian residues, and cellular immunity.40,41 However, none of these theories comprehensively accounts for the mechanism and the different biological and clinical characteristics of endometriosis alone. According to literature, the formation and maintenance of ectopic endometrial lesions at ectopic sites are the most basic characteristics of endometriosis and are strongly correlated with the pathology and pathogenesis, such as inflammation, oxidative stress, proliferation, apoptosis, angiogenesis, immunity, invasion, and adhesion.4247 It has also been found that some other factors, such as hormones, heredity, and environment, are implicated in the formation and/or advancement of this disease. Local estrogen augmentation and progesterone resistance are observed in endometriosis, thus promoting the survival, migration, proliferation, and adhesion of ectopic endometrial cells. According to a previous report, first-degree relatives of patients affected by endometriosis have a 710 times increased risk of developing endometriosis,48 and studies in female twins have revealed that the heritability of endometriosis may be up to 50%.2 Several experimental studies on primates and rodents have shown that exposure to tetrachlorodibenzo-p-dioxin (TCDD) and other organochlorine environments (particularly dioxin-like compounds) during adulthood interfere with hormone regulation and immune function, thereby facilitating endometriosis.49

Endometriosis is a proliferative chronic disorder that is mainly characterized by the abnormal endometrial growth at ectopic sites outside the uterine cavity.42 Previous studies have shown an incremental cell proliferation rate of ectopic endometrium in endometriotic patients, which is conductive to survival and implantation into the ectopic site.50 Proliferating cell nuclear antigen (PCNA), a sensitive indicator of proliferation and DNA restoration, exists in the G1, S and G2 phases of the cell cycle, while Ki-67 exists in all active phases and is a more specific proliferative marker than PCNA.51 The proliferative ability of cells is usually be assessed by detecting the expression of proliferative markers.

Bruner-Tran et al firstly evaluated the curative potential of resveratrol on endometriosis in an animal model of endometriosis and endometrial tissues, and they reported that resveratrol reduces the incidence of experimental endometriosis and also decreases the invasion of normal endometrial stromal cells (NESCs) in vitro.51 Additionally, they demonstrated that resveratrol attenuates the formation and advancement of endometriosis by suppressing cell proliferation, promoting apoptosis, and reducing invasiveness. However, the efficacy of resveratrol against proliferation in ectopic endometrial lesions remains unclear as they reported to upregulate expression of PCNA but to downregulate expression of Ki-67 in implants.51

In peritoneal and mesenteric endometriosis rat model, Rudzitis-Auth et al reported that resveratrol treatment reduces the number of PCNA+ and Ki-67+ endometrial cells, thereby mitigating the growth rate of endometriotic implants compared to the control group. In addition, they demonstrated that resveratrol suppresses the formation of novel microvasculature in endometriotic implants by inhibiting the proliferative activity of CD31+ endothelial cells.52

Apoptosis is the process of programmed cell death, that helps sustain intracellular homeostasis by scavenging dysfunctional cells from the endometrium during the menstrual cycle.43 Compared to healthy participants, patients affected by endometriosis have impaired spontaneous apoptosis of ectopic and eutopic endometrium, leading to growth and implantation of endometrial tissues at ectopic areas.53 This resistance to apoptosis is associated with increased expression of anti-apoptotic factors (eg, B-cell lymphoma-2 (Bcl-2)) and decreased expression of pro-apoptotic factors (eg, caspase-3, Bcl-2 associated X (Bax)).53,54

To date, the effect of resveratrol on cell apoptosis in endometriosis has been evaluated through several animal models and in vitro experiments. Madanes et al investigated the mechanism of resveratrol in endometrial cells, and they reported that this compound remarkably reduces cell viability and induces apoptosis by increasing caspase-3 cleavage in two cell lines, namely, endometriotic epithelial cells (12Z) and endometrial stromal cells (St-T1b).55 The property of invasiveness depends on the ratio of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs).56 Furthermore, resveratrol mitigates the ability of invasion and angiogenesis by lowering the gene expression ratio of MMP-2/TIMP-1 and suppressing the mRNA expression of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1).55

In an in vitro three-dimensional culture model of endometriosis, Khazaei et al investigated the effects of resveratrol at various doses on human endometrial overgrowth, neovascularization, and the expression of apoptosis-related genes, and they reported that resveratrol attenuates the growth of endothelial cells, stromal and epithelial cells in a dose-dependent manner.57 Furthermore, these researchers demonstrated that resveratrol fully inhibits growth and angiogenesis at a concentration of 200 M. They also reported that resveratrol decreases the level of nitric oxide (NO, a vasodilator and messenger molecule in the process of angiogenesis), and significantly increases the expression levels of pro-apoptotic genes, such as Sirtuin-1 (SIRT1), Bax, caspase-3 and p53, and decreases the ratio of Bax/Bcl-2.57 Additionally, another study has assessed the influence of resveratrol on Bax and Bcl-2 gene expression within ectopic endometrial stromal cells (EcESCs), eutopic endometrial stromal cells (EuESCs), and NESCs, demonstrating that resveratrol intervention effectively decreases the gene expression ratio of Bax/Bcl-2 in EuESCs and NESCs but not in EcESCs.58

In addition to the aforementioned effects of resveratrol on endometriosis, a previous study has demonstrated that pretreatment with resveratrol diminishes the level of the anti-apoptotic protein, survivin, as well as suppresses the apoptosis resistance of EcESCs and accelerates apoptosis induced by tumor necrosis factor-alpha (TNF-) related apoptosis-inducing ligand (TRAIL).59

Angiogenesis, the formation of neovascularization, is a sophisticated multistage procedure that includes the following processes: coordinated expression of genes encoding angiogenic growth factors, disintegration of extracellular matrix, migration and proliferation of endothelial cells, and formation of capillary tubes.60 Because the implantation, proliferation, and growth of endometriotic lesions require a new blood supply, angiogenesis plays an essential role in the establishment and maintenance of endometriotic lesions.44 Based on the literature, increased levels of cytokines related to angiogenesis, such as VEGF, MMPs, TNF-, interleukin-6 (IL-6), IL-8, transforming growth factor-beta (TGF-), hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF-1), platelet-derived growth factor (PDGF), angiopoietin, macrophage migration inhibitory factor (MIF), erythropoietin, neutrophil activating factor, and tissue factor (TF), have been measured in the peritoneal fluid (PF) of endometriotic patients compared to disease-free women.6163 Moreover, inflammation, oxygen deficiency, endothelial cell damage, and disturbances in acid-base imbalance also facilitate the formation of new blood vessels.64,65 These factors are collectively implicated in the angiogenesis of endometriosis.

VEGF, the most prominent angiogenic factor in endometriosis,63 which is produced by EcESCs, EuESCs, peritoneal macrophages, and neutrophils, triggers endothelial cell proliferation, migration, and survival during the process of angiogenesis, and it increases vascular permeability, thus enhancing the development of endometriosis.66,67 Compared to the non-endometriotic controls, markedly increased levels of VEGF have been detected in the PF, serum, EcESCs and EuESCs of endometriotic women, and the level is linked to the clinical stage.6870 However, there is no distinction in VEGF levels in either blood or urine.71 TGF- is involved in mediating numerous cell functions, such as cell proliferation, apoptosis, angiogenesis, inflammation, migration, adhesion, differentiation, tumor inhibition, and immune functions. TGF- may promote the survival of ectopic endometrial cells, strengthen apoptosis resistance, accelerate invasion, and initiate neoangiogenesis by inducing alterations in cellular metabolism, thereby leading to the progression of endometriosis.72 Compared to the non-endometriotic controls, the levels of TGF- in serum, PF, ectopic endometriotic lesions, and peritoneal tissue of endometriotic patients are higher, and it is linked to the degree of inflammation.73,74

To evaluate the anti-angiogenic effects of resveratrol, a previous study applied resveratrol to treat endometriosis in a mesenteric endometriosis rat model as well as treated EuESCs and NESCs with resveratrol. Ricci et al suggested that resveratrol diminishes the vascular density and reduces the numbers and volumes of endometriotic lesions.75 They also reported that resveratrol suppresses cell proliferation and promotes cell apoptosis, further inhibiting the occurrence and development of endometriotic lesions.75

Two studies have evaluated the therapeutic efficacy of resveratrol in an experimental rat model and compared this effect to leuprolide acetate, a GnRH analog, demonstrating that the effectiveness of resveratrol on endometriosis is equivalent to that of leuprolide acetate. Both resveratrol and leuprolide acetate have the following effects: significantly decrease the volume and histopathological scores of endometriotic lesions, downregulate the expression of VEGF, MMP-2, and MMP-9 in implants, reduce the levels of monocyte chemoattractant protein-1 (MCP-1) and VEGF in serum and PF, and reduce the levels of TNF-, IL-6, and IL-8 in plasma and PF. Interestingly, the drug combination of resveratrol and leuprolide acetate represses the anti-angiogenic and anti-inflammatory efficacy compared to treatment with each drug alone.76,77 Additionally, Ergenolu et al reported that resveratrol treatment in a rat endometriosis model minimizes the size of endometriosis lesions and decreases VEGF level in the PF and plasma as well as downregulates VEGF expression in endometriotic lesions.78

Bahrami et al reported that resveratrol, atorvastatin alone, and particularly the combination of resveratrol and atorvastatin diminish the size of endometriotic lesions, reduce the number of new blood vessels, and inhibit the expression of glycolysis-related proteins, such as glucose transporters-1 (GLUT-1) and GLUT-3 and monocarboxylate transporters-1 (MCT-1) and MCT-4 in a rat model of endometriosis, suggesting that resveratrol inhibits the establishment and development of ectopic endometrial tissue by suppressing glycolysis and angiogenesis.79

In vitro experiments have revealed higher basic gene and protein expression levels of VEGF, MMP-9, IGF-1, and HGF in EcESCs compared to EuESCs and NESCs, and resveratrol intervention significantly reduces the gene and protein expression levels of VEGF, MMP-9, and TGF- in EcESCs and EuESCs, as well as downregulates the gene expression levels of VEGF and MMP-9 in NESCs.80,81 Reduced expression of IGF-1 and HGF has also been observed in EcESCs and EuESCs after resveratrol intervention, especially in EcESCs, which are effective promotors of ectopic endometrial lesions, owing to their role in growth, proliferation, invasion, and angiogenesis.80,81

Khodarahmian et al conducted a randomized exploratory clinical study, in which endometriotic patients with stage IIIIV were treated with resveratrol (400 mg) or placebo for 12 to 14 weeks in addition to COCs.82 The results show that resveratrol remarkably reduced the protein and gene expression levels of TNF- and VEGF in eutopic endometrial tissues, compared to the control group and before intervention. Thus, they suggested that resveratrol mitigates angiogenesis and inflammation in the endometrium of endometriotic patients by undermining the expression of TNF- and VEGF.82

Endometriosis, an inflammatory disease, is relevant to chronic inflammation and immune dysregulation in the peritoneal microenvironment.45 Several studies have reported that levels of pro-inflammatory cytokines and chemokines, such as IL-1, IL-4, IL-6, IL-8, IL-12, TGF-, TNF-, prostaglandin (PG), growth factor, MCP-1, and regulated upon activation, normal T cell expressed and secreted (RANTES), are higher in the PF of women affected by endometriosis compared to disease-free participants.8385 These inflammatory mediators may participate in the establishment and advancement of endometriosis, and they are secreted by activated macrophages, lymphocytes, endometriotic lesions, and peritoneal mesothelial cells, thereby promoting the viability, proliferation, adhesion, invasiveness, and angiogenesis of endometrial cells.86

Macrophages are the most common member of the immune cell family in endometriosis, and activated macrophages modulate the peritoneal microenvironment through phagocytosis and secretion of immune mediators.85 M1 and M2 are two main categories of activated macrophages, M1 predominantly participate in the pro-inflammatory response, inhibit cell proliferation, and exacerbate tissue damage, while M2 mainly participate in anti-inflammatory reactions, tissue repair, and angiogenesis.87,88 Evidences suggest that in endometriotic women, the macrophages in the eutopic endometrium are mostly M1-polarized, while those in the ectopic endometrium are mostly M2-polarized.89 Macrophages depletion tests have demonstrated that M2 enhance the growth and vascularization of endometriotic lesions, while M1 effectively protect mice from endometriosis.90 In an experimental endometriosis rat model, Wang et al reported that the number of activated macrophages is increased in the PF, which agreed with other studies. However, they reported that M1/M2 polarization in the PF is increased and resveratrol reduces the M1/M2 polarization, which contradicts other studies.91 The inconsistent conclusions may be explained by the measurement of different samples. Wang et al detected macrophage polarization in the PF, while other researchers detected macrophage polarization in endometriotic lesions. Additionally, Wang et al reported that resveratrol decreases the mRNA expression levels of the pro-inflammatory cytokines IL-6, TNF-, and interferon gamma (INF-) but increases the mRNA expression levels of the anti-inflammatory IL-10.91

MCP-1, also known as chemokine (C-C motif) ligand 2 (CCL2), binds to its receptor, CCR2, and then activates the signaling pathways regulating cell migration, further promoting the migration of inflammatory cells, such as monocytes/macrophages, and infiltration of other cytokines in the inflammatory site.92 MCP-1 is generated by fibroblasts, macrophages, endothelial cells, epithelial cells, EcESCs, and EuESCs.86,92 Some studies have demonstrated that the expression level of MCP-1 in the serum, PF, and EcESCs is higher in endometriotic patients than in non-endometriotic controls.93,94 Heidari et al assessed the effects of resveratrol on endometriosis by isolating EcESCs and EuESCs from endometriotic patients and NESCs from disease-free participants.87 They demonstrated that the protein and gene expression levels of MCP-1 were higher in EcESCs compared to EuESCs and NESCs under basic conditions, but that resveratrol (100 M) intervention significantly downregulates the expression of MCP-1 and RANTES in EcESCs.87 Similarly, other studies have reported that resveratrol reduces MCP-1 level in the PF of endometriotic animal models.76,78

IL-6, an inflammatory cytokine, stimulates M2 polarization of peritoneal macrophages, weakens phagocytosis of macrophages, reduces cytotoxicity of natural killer (NK) cells, and facilitates the synthesis of aromatase, consequently promoting the progression of endometriotic lesions.89,9597 IL-8, a pro-inflammatory, pro-angiogenic, and growth-promoting cytokine, enhances the expression of various adhesion molecules and neutrophil chemotaxis, and it may also promote the initial adherence of endometrial cells to the peritoneum surfaces.98 Numerous studies have reported that the levels of IL-6 and IL-8 in the PF and serum of endometriotic patients are significantly higher than those in individuals without endometriosis and they increase correspondingly with the aggravation of endometriosis stage.93,98,99 Additionally, the levels of IL-6 and IL-8 are higher in EcESCs compared to EuECSs,100 and the increased expression of IL-6 and IL-8 increases the migration and invasion abilities of EcESCs.99,101 Using an experimental endometriosis model, Bayoglu Tekin et al revealed that resveratrol reduces the levels of IL-6 and IL-8 in the PF and serum compared to the control group.77 Consistent with their findings, another study has evaluated the impacts of resveratrol on IL-6 and IL-8 mRNA and protein expression in EcESCs, EuESCs, and NESCs, demonstrating that resveratrol reduces the expression of IL-6 and IL-8 in EcESCs compared to the EuESCs and NESCs groups.86

TNF- is implicated as a pivotal factor in the inflammatory response and immunopathological injury.102 Previous studies have reported that ectopic endometrial tissue stimulates humoral and cellular immunity, acting as an antigen, which results in an increased number and activity of macrophages and lymphocytes, thereby increasing the expression of TNF-.103 The level of TNF- is increased in the PF and serum of endometriotic women, and it is closely related to the stage of endometriosis, which may contribute to the production of other cytokines and the proliferation, adhesion, and angiogenesis of endometrial cells.103,104 Similarly, in vitro, animal, and clinical exploratory experiments have demonstrated that resveratrol decreases the levels of TNF- in the PF and endometrial tissues of the endometriosis groups.77,91,105 Other studies have reported that resveratrol alleviates TNF--stimulated inflammatory injury in late-stage endothelial progenitor cells (EPCs) by reducing the expression of intercellular adhesion molecule 1 (ICAM-1) and MCP-1.106 Additionally, resveratrol suppresses the invasiveness of human hepatoma cells by inhibiting nuclear factor-kappa B (NF-B) activity to reduce TNF--mediated MMP-9 expression.107

SIRT1 is involved in the modulation of inflammation. The increased activity and overexpression of SIRT1 suppresses the production of inflammatory cytokines,108,109 while SIRT1 deficiency stimulates the inflammatory response.110 SIRT1 also has a role in oxidative stress. Resveratrol treatment can reverse the experimental induced oxidative stress condition and upregulate SIRT1 expression.111 Taguchi et al reported that resveratrol ameliorates local inflammation in endometriosis by suppressing TNF--induced IL-8 release in a dose-dependent manner via the SIRT1 pathway.112

Cyclooxygenase-2 (COX-2), a rate-limiting enzyme of prostaglandin E2 (PGE2) biosynthesis,113 is an essential part of the positive feedback circulation of estradiol (E2)-COX-2-PGE2-aromatase-E2, and upregulated COX-2 expression decreases apoptosis and promotes proliferation, invasiveness, angiogenesis, endometriosis-related pain, and infertility.114 The expression of COX-2 in the ectopic and eutopic endometrium of endometriotic women is upregulated compared to the normal endometrium of disease-free individuals.115 In a clinical trial, Maia et al reported that resveratrol promotes the effectiveness of COCs to alleviate dysmenorrhea by downregulating the expression of COX-2 and aromatase in the endometrium.116 Nonetheless, another clinical study has reported that resveratrol has no advantage over placebo in treating endometriosis-related pain.117

Oxidative stress is characterized by an imbalance between anti-oxidant defense and oxidation,118 resulting in the accumulation of ROS and oxidation products as well as causing damage to molecules, cells, and the organisms. ROS mediate cytotoxicity by interacting with lipids, proteins (especially cysteine residues), and nucleic acids.119 Based on data from previous research, the oxidative stress of endometriosis is associated with increased ROS and oxidation products, reduced anti-oxidant enzymes and detoxifying enzymes, disordered iron metabolism, and elevated number of activated macrophages. An increased level of oxidative stress gives rise to inflammation, angiogenesis, cell proliferation, cell adhesion, and extracellular matrix degradation, resulting in endometriosis and infertility.47,120,121

NF-B, a transcription factor, modulates the expression of a variety of genes encoding angiogenic factors, growth factors, pro-inflammatory factors, chemokines, and adhesion molecules, such as ICAM-1, as well as inducible enzymes, such as inducible nitric oxide synthase (iNOS) and COX-2.122,139 These gene products facilitate cell proliferation, adhesion, inflammation, angiogenesis, and oxidative stress, thereby implicating the progression of endometriosis.123 NF-B initiates gene transcription of gp91-phox, the catalytic subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which is implicated in the electron transport chain of oxidative phosphorylation and responsible for donating electrons from NADPH to molecular oxygen to generate superoxide anion, consequently increasing oxidative stress.119 Another study has reported that NF-B-mediated transcriptional activation of COX-2 also inhibits apoptosis and promotes cell proliferation in endometriosis.124 Oxidative stress and iron overload activate the NF-B signaling pathway and elevate IL-10 levels in the serum and PF of patients affected by endometriosis, leading to MMPs activation, extracellular matrix (ECM) remodeling, and neovascularization.115 Elevated levels of INF- and IL-10 resulting from increased IL-2 and IL-27 are able to collaboratively accelerate the proliferation and invasion of endometrial stromal cells.125

The role of oxidative stress in endometriosis is generally assessed by ROS markers, including malondialdehyde (MDA), oxidative products, and enzyme antioxidants, such as glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD).126 Using resveratrol in experimental endometriosis rats, Yavuz et al showed that resveratrol increases SOD and GSH-Px activities in ectopic endometrial tissues and serum in a dose-dependent manner as well as increases CAT levels in tissues.127 And they reported that resveratrol reduces MDA levels in tissues and serum but not to a significant extent compared to the control group. Whats more, resveratrol effectively diminishes implant sizes, histological scores, and PCNA expression levels were observed. And they demonstrated that resveratrol inhibits oxidative stress by activating endogenous antioxidant capacity to ameliorate endometriosis.127 In diazinon (DZN)-induced oxidative stress rat models, Mehri et a reported that DZN inhibits serum acetylcholinesterase (AChE) as well as serum and liver CAT, GSH-Px, and total antioxidant abilities, and they also demonstrated that resveratrol reverses the oxidative stress conditions, improves the activity of antioxidant enzymes, and lower MDA level in the serum and liver.111

In view of Sampsons theory, invasion and adhesion are key processes in the establishment of endometriosis.128 Elevated levels of MMPs, especially MMP-2 and MMP-9, as well as cell adhesion molecules, such as ICAM-1, integrin, and cadherin, have been reported in the PF of endometriotic women, which collectively exert influences on the invasion and adhesion of ectopic endometrium.46,129,130

MMPs, a group of zinc-dependent proteolytic enzymes, play an important role in the degradation of ECM, which is a vital step of ectopic endometrial cell implantation and endometriosis formation.131 A comprehensive analysis of previous studies has revealed that MMPs are implicated in multiple stages associated with endometriosis formation as follows: endometrial cells migrating from the uterine cavity and implanting in peritoneal surfaces, vascular endothelial cells migrating to new blood vessels, macrophages distinguishing and phagocytizing escape cells, and NK cells killing target cells. These stages promote cell migration, cell invasion, angiogenesis, ephemeral mesenchymal transformation (EMT), fibrosis, and regulation of immune cells or autoimmune factors, ultimately inducing endometriosis.132 ECM protein degradation and tissue remodeling play pivotal roles in ectopic endometrial cell implantation and endometriotic lesion formation, and the extent of which is generally determined by the MMP/TIMP ratio.133 PGE2 and COX-2 can facilitate angiogenesis indirectly by mediating MMP-2 activity.113 Chen et al revealed that resveratrol reduces invasiveness and proliferation as well as induces early apoptosis of EcESCs in a dose-dependent manner.134 Moreover, they reported that resveratrol effectively reduces the gene expression of VEGF, Bcl-2 and MMP-2 as well as the protein expression levels of ICAM-1 and MMP-2. Additionally, they showed that resveratrol corrects aberrant lipid distribution in endometriosis model rats.134 An exploratory clinical trial has indicated that the gene and protein expressions levels of MMP-2 and MMP-9 are significantly decreased within endometrial tissues, endometrial fluid, and serum after resveratrol intervention compared to controls.105

EMT is the trans-differentiation of epithelial cells into mesenchymal cells. Zinc-finger E-box-binding (ZEB) and other transcription factors drive EMT by increasing mesenchymal maker (eg, vimentin) expression and decreasing epithelial marker (eg, E-cadherin) expression, which further degrades the extracellular matrix, promoting invasion ability.132,135 To the best of our knowledge, metastasis-associated protein 1 (MTA1) induces EMT in a variety of cancers to promote disease progression and metastasis,136 and it is overexpressed in endometrial cancer to promote carcinoma cell proliferation, migration, and invasion.137 A thorough exploration of the Gene Expression Omnibus (GEO) database has indicated that the expression levels of MTA1 and ZEB2 are upregulated in ectopic endometrial tissues.138 Kong et al found that MTA1 interacts with ZEB2 to induce EMT, thus facilitating the proliferation, migration, and invasiveness of NESCs, while resveratrol downregulates the expression of MTA1 and ZEB2 as well as inhibits their promoting function.138 In an endometriosis mouse model, compared with the eutopic endometrium, the expression of MTA1, ZEB2, and vimentin is increased in endometriotic implants, but E-cadherin expression is decreased, however, resveratrol reverses these phenomena by inhibiting the growth of ectopic endometrium and suppressing the expression of MTA1, ZEB2, and vimentin as well as promoting the expression of E-cadherin.138

Endometriosis is regarded as hormone-dependent as several studies have reported that the endometrium is modulated by steroid hormones, mainly including estrogen and progesterone, which regulate the expression of various genes at diverse stages of the menstrual cycle.140 The level of estrogen detected in the ectopic endometrium of endometriotic women is elevated compared to that in the eutopic endometrium or normal endometrium, which depends on local estrogen metabolism rather than circulating levels.141 Ectopic endometrial tissues can synthesize abundant E2 de novo from cholesterol, resulting from the high expression of aromatase (the key enzyme for estrogen biosynthesis) and steroidogenic acute regulatory protein (StAR), while normal endometrial tissues cannot synthesize estrogen due to the lack of these enzymes.142 Moreover, some inflammatory factors are also involved in the synthesis of local E2. The elevated level of COX-2 increases the expression of PGE2, which activates the aromatase gene promoter, resulting in aromatase overexpression and accumulation. Furthermore, E2 stimulates the expression of COX-2 by binding to its receptor, estrogen receptor beta (ER). Thus, estrogen generation and chronic inflammation form a vicious spiral under the positive feedback cycle of E2-COX-2-PGE2-aromatase-E2.114

Because immunoreactive ER and progesterone receptor (PR) exist in ectopic and eutopic endometrium, they show similar histological changes in response to estrogen and progesterone.143 PR-A and PR-B are the main subtypes of PRs in the endometrium, of which PR-B plays more important biological functions. In EcESCs of endometriotic patients, the methylation of the PR-B transcription factor is enhanced, resulting in progesterone resistance, which is consistent with the report that EuESCs of women with endometriosis are less responsive to progesterone.144 ERs in the endometrium mainly consist of ER and ER. The expression of ER is more prominent in healthy endometrial tissues, while the expression of ER is more prominent in ectopic endometrial tissues.145 The ER level in EcESCs cultured in vitro is 142 times higher than that in NESCs, while the ER level in EcESCs is 9 times lower than that in NESCs.146 ER and ER may be cooperatively responsible for the regulation of proliferation, adhesion, and inflammation in the initiation of endometriotic lesions. Besides, ER principally triggers angiogenesis, and ER exerts a leading role in the pro-invasive capability, anti-apoptotic effects and activation of inflammatory bodies to maintain survival.147

Using an experimental animal model, Han et al showed that overexpressed ER in ectopic endometrium attenuates TNF--induced apoptosis, elevates the level of IL-1 to promote inflammation, and enhances EMT to facilitate invasion and adhesion.147 Amaya et al suggested that resveratrol is an estrogen agonist or antagonist at lower or higher levels, respectively.39 Their another study using a recombination activating gene-2 mouse model of endometriosis has demonstrated that the expression of Ki-67 and ER in the endometrial epithelium is downregulated, and that ER is reduced to a level similar to that with progesterone treatment. However, progesterone treatment dose not decrease the Ki-67 expression level. Therefore, these researchers proposed that high-dose resveratrol reduces proliferation activity of the endometrial epithelium by inhibiting ER expression.39

Resveratrol mostly exists in dietary foods in a glycosylated form, which prevents resveratrol from enzymatic oxidation in the digestive tract, thus preserving its biological activity and overall stability.148,149 However, intestine cells absorb only resveratrol aglycone via transepithelial diffusion with an absorption rate of approximately 75%. Pharmacokinetics studies have confirmed that resveratrol is rapidly and comprehensively metabolized through the intestine and liver, and the main glucoside and sulfate metabolites of resveratrol are produced through glucuronidation and sulfation.149,150 Therefore, it has been proposed that improving the content of resveratrol glycosylation and aglycone may increase its absorption rate in foods and beverages.151 Despite good lipophilicity and a high absorption rate, these coupling reactions (glucuronidation and sulfation) also decrease cell permeability to the drug, increase the polarity of the drug, and promote drug excretion from the body. Evidence suggests that after extensive metabolism of resveratrol in the intestines and liver, nearly 75% of the metabolites are scavenged from the body through urine and feces, ultimately, the oral bioavailability of resveratrol is less than 1%.149,152 Thus, the limited effect of resveratrol results from its rapid metabolic rate in vivo.153

Walle et al reported that the plasma concentration of resveratrol is less than 10 ng/mL following oral administration of 25 mg resveratrol in humans, and the plasma concentration is 500 ng/mL after taking 5000 mg of high-dose resveratrol, indicating that increased or repeated dose of resveratrol does not significantly improve the bioavailability.149 To date, it is generally believed that the limited bioavailability of resveratrol is largely due to its poor water solubility, thus, a variety of formulations and strategies have been developed, including nanocarriers, liposomes, and synthetic derivatives (aromatic rings contain different substituents, such as methoxy, hydroxyl, or halogen), to improve the bioavailability.154156 Compared to free resveratrol, some studies have reported that resveratrol nanoparticles increase the uptake and sustained release in target cells as well as the toxicity of resveratrol to these cells, thereby improving the bioavailability,157 and the absorption rate of resveratrol nanoparticles conjugated with polyethylene glycol is increased by 7-fold.158 Methylation of resveratrol enhances the water solubility and bioavailability of resveratrol, and Summerlin et al proposed that methylated resveratrol synthesized by in vitro metabolic engineering (recombinant Escherichia coli) is superior to chemosynthesis in biological activity.157 Importantly, in the process of drug research and development, attention should be focused on amending the structure, bioavailability and activity of resveratrol.

Comprehensive testing has indicated that oral administration of resveratrol is considered safe.159 A previous rat experiment has demonstrated that resveratrol effectively suppresses the growth of ovarian cancer but does not affect normal tissues.160 Another study has reported that resveratrol regulates the proliferation and apoptosis of cancer cells and epithelial cells in a dose-dependent manner. Resveratrol exerts a time- and concentration-dependent pro-apoptotic impact on cancer cells.161 Besides, resveratrol protects healthy cells and induces cancer cell death, which may be due to its inconsistent molecular targets and metabolic pathways within these cells.162 Experimental animal models have shown good tolerance to resveratrol. For instance, CD rats receiving resveratrol at a daily dosage of 200 mg/kg and beagle dogs receiving resveratrol at a daily dosage of 600 mg/kg for 90 days do not show any obvious biological adverse effects.163 In CD rats, a high daily dose of resveratrol (1000 mg/kg, lasting for 1013 weeks) increases the level of bilirubin without any gross or microscopic changes associated with liver injury, and the high dose of resveratrol administration reduces the incidence of cardiomyopathy. Notably, elevated bilirubin has not been reported in beagle dogs exposed to any dose level of resveratrol.163

By evaluating the potential toxicity of resveratrol, Crowell et al reported that rats fed resveratrol at a high daily dosage (3000 mg/kg, lasting for 4 weeks) show elevated levels of transaminase, bilirubin, creatinine, and blood urea nitrogen (BUN) as well as increased incidence and severity of nephrosis but with no histological changes in the liver.164 Liu et al used an experimental renal fibrosis mouse model to estimate the impact of resveratrol on renal fibrosis.165 They found that resveratrol at low dosage (25 mg/kg) partially ameliorates kidney function by mitigating unilateral ureteric blockage, while a high dosage (50 mg/kg) fails to prevent fibrosis and aggravates renal fibrosis in mice. These researchers also concluded that mice with ureteric blockage are more predisposed to kidney injuries induced by high-dose resveratrol than normal mice.165 Some researchers have considered that the effective dosage range of this compound in cells is inconsistent with the concentration in the human body, therefore, it is difficult to ascertain the efficacious concentration range of resveratrol in participants.166 The safety of resveratrol in humans has been assessed at different doses in several clinical studies, and these studies have indicated that resveratrol has no obvious adverse effects.167173 Resveratrol is safe and well-tolerated in a disease-free population following a single dose of 500 mg resveratrol tablet.172 Another study has suggested that resveratrol is considered to be safe at daily doses up to 5000 mg and these slight adverse effects, such as alopecia, nausea, headache, and diarrhea, occur only when taking a high oral dose of resveratrol (>2500 mg, every 4 hours).173 Since these studies on the toxicity of resveratrol were conducted in endometriosis-free participants, it is possible that the side effects of resveratrol may vary in patients with endometriosis.

As a substitute or supplement treatment for endometriosis, resveratrol is a promising candidate. To date, however, the clinical trials evaluating the role of resveratrol in endometriosis have been small samples and lack an assessment of its side effects. 82,105,116,117 The optimal drug dosage to maximize the health benefits of resveratrol without causing toxicity requires further supporting evidence, suggesting that additional comprehensive studies are needed.29,166 Furthermore, it is not easy to determine the therapeutic effect of resveratrol at a specific dosage as well as the precise dosage safety range in patients with endometriosis. Thus, the optimum dosage and preparation method of resveratrol need to be further explored.

Botanical therapies (or herbal medicines) have been used to combat diseases for a long time in human history, especially for infectious diseases, cancer, and other chronic ailments. The basis of these synergistic therapeutic effects of the therapies and herbal medicines is bioactive compounds within the mixtures or crude preparations. More precisely and scientifically, compounds found in the natural sources (eg, plants, animals, microorganisms, and minerals) are defined as natural products (NPs). Due to their vast scaffold diversity, structural complexity, and stability, NPs have received much attention in the drug discovery process. To date, many successfully approved drugs have been derived from NPs, such as Taxol (oncology), Fumagillin (antiparasitic), Trabectedin (oncology).

Resveratrol, a natural product, is mainly found in the grapes and red wines, and it also exists in some other plants and several genera of microorganisms. Based on in vitro, animal, and clinical studies associated with endometriosis, resveratrol has been reported to have multiple biological functions, such as anti-proliferative, pro-apoptotic, anti-angiogenic, anti-oxidant, anti-invasive, and anti-adhesive effects. Accumulated evidences confirm that resveratrol is a relatively safe and well-tolerated compound for humans, but it is also an inefficient agent due to its rapid metabolic rate in vivo. Nanocarriers, liposomes, and synthetic derivatives of resveratrol have been explored to increase its biological availability. In the light of existing evidence, resveratrol is effective and potential in endometriosis, we speculate that resveratrol may be a new supplementary and adjuvant drug for the treatment of endometriosis. However, the exact molecular mechanisms are not fully elucidated, and the majority of studies have been conducted on in vitro and rodent animal models, with a few clinical studies. Furthermore, there are distinctions in the reproductive physiology between humans and rodents because rodents never develop endometriosis spontaneously due to a lack of menstruation. Consequently, caution is always warranted when extrapolating results obtained from in vitro experiments or animal models to humans, and further high-quality clinical trials with large sample sizes should be implemented to assess the effectiveness and clinical application feasibility of resveratrol in endometriosis.

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

This research was funded by the Doctoral Research Initiation Fund of the Affiliated Hospital of Southwest Medical University (No. 18061), the Fund for High-level Talents in Luzhou City (No. 02/00180117).

The authors report no conflicts of interest in this work.

1. Andres MP, Arcoverde FVL, Souza CCC, Fernandes LFC, Abro MS, Kho RM. Extrapelvic endometriosis: a systematic review. J Minim Invasive Gynecol. 2020;27(2):373389. doi:10.1016/j.jmig.2019.10.004

2. Zondervan KT, Becker CM, Missmer SA, Longo DL. Endometriosis. N Engl J Med. 2020;382(13):12441256. doi:10.1056/NEJMra1810764

3. Garcia-Fernandez J, Garca-Velasco JA. Endometriosis and reproduction: what we have learned. Yale J Biol Med. 2020;93(4):571577.

4. Prosperi Porta R, Sangiuliano C, Cavalli A, et al. Effects of breastfeeding on endometriosis-related pain: a prospective observational study. Int J Environ Res Public Health. 2021;18(20):10602. doi:10.3390/ijerph182010602

5. Armour M, Lawson K, Wood A, Smith CA, Abbott J, Thumbikat P. The cost of illness and economic burden of endometriosis and chronic pelvic pain in Australia: a national online survey. PLoS One. 2019;14(10):e0223316. doi:10.1371/journal.pone.0223316

6. Halici BNA, Aktoz F, Kabakci M, Kiran G, Ozcan P. Analysis of preoperative and postoperative quality of life, sexual function, and sleep in patients with endometriosis: a prospective cohort study. Arch Gynecol Obstet. 2022;307(1):113120. doi:10.1007/s00404-022-06562-9

7. Kim HS, Kim TH, Chung HH, Song YS. Risk and prognosis of ovarian cancer in women with endometriosis: a meta-analysis. Br J Cancer. 2014;110(7):18781890. doi:10.1038/bjc.2014.29

8. Kajiyama H, Suzuki S, Yoshihara M, et al. Endometriosis and cancer. Free Radic Biol Med. 2019;133:186192. doi:10.1016/j.freeradbiomed.2018.12.015

9. Kalaitzopoulos DR, Samartzis N, Kolovos GN, et al. Treatment of endometriosis: a review with comparison of 8 guidelines. BMC Womens Health. 2021;21(1):397. doi:10.1186/s12905-021-01545-5

10. Qin Z, Dong Z, Liu J, et al. A preliminary study on the effects of black cohosh preparations on bone metabolism of rat models with GnRH-a-induced peri-menopausal symptoms. Front Endocrinol. 2022;13:854345. doi:10.3389/fendo.2022.854345

11. Chen J, Wang H, Dong Z, et al. GnRH-a-induced perimenopausal rat modeling and black cohosh preparations effect on rats reproductive endocrine. Front Endocrinol. 2021;12:683552. doi:10.3389/fendo.2021.683552

12. Corte LD, Noventa M, Ciebiera M, et al. Phytotherapy in endometriosis: an up-to-date review. J Complement Integr Med. 2020;17(3). doi:10.1515/jcim-2019-0084

13. Zakhari A, Delpero E, McKeown S, Tomlinson G, Bougie O, Murji A. Endometriosis recurrence following post-operative hormonal suppression: a systematic review and meta-analysis. Hum Reprod Update. 2021;27(1):96107. doi:10.1093/humupd/dmaa033

14. Guo SW. Recurrence of endometriosis and its control. Hum Reprod Update. 2009;15(4):441461. doi:10.1093/humupd/dmp007

15. Mikus M, Vitale SG, Coric M, et al. State of the art, new treatment strategies, and emerging drugs for non-hormonal treatment of endometriosis: a systematic review of randomized control trials. Gynecol Endocrinol. 2022;38(11):911917. doi:10.1080/09513590.2022.2133105

16. Malaguarnera L. Influence of resveratrol on the immune response. Nutrients. 2019;11(5):946. doi:10.3390/nu11050946

17. Yuan L, Zhou M, Huang D, et al. Resveratrol inhibits the invasion and metastasis of colon cancer through reversal of epithelial mesenchymal transition via the AKT/GSK3/Snail signaling pathway. Mol Med Rep. 2019;20(3):27832795. doi:10.3892/mmr.2019.10528

18. Galiniak S, Aebisher D, Bartusik-Aebisher D. Health benefits of resveratrol administration. Acta Biochim Pol. 2019;66(1):1321. doi:10.18388/abp.2018_2749

19. Kasiotis KM, Pratsinis H, Kletsas D, Haroutounian SA. Resveratrol and related stilbenes: their anti-aging and anti-angiogenic properties. Food Chem Toxicol. 2013;61:112120. doi:10.1016/j.fct.2013.03.038

20. Rodrguez-Enrquez S, Pacheco-Velzquez SC, Marn-Hernndez , et al. Resveratrol inhibits cancer cell proliferation by impairing oxidative phosphorylation and inducing oxidative stress. Toxicol Appl Pharmacol. 2019;370:6577. doi:10.1016/j.taap.2019.03.008

21. Fu X, Li M, Tang C, Huang Z, Najafi M. Targeting of cancer cell death mechanisms by resveratrol: a review. Apoptosis. 2021;26(1112):561573. doi:10.1007/s10495-021-01689-7

22. Burns J, Yokota T, Ashihara H, Lean ME, Crozier A. Plant foods and herbal sources of resveratrol. J Agric Food Chem. 2002;50(11):33373340. doi:10.1021/jf0112973

23. Sales JM, Resurreccion AV. Resveratrol in peanuts. Crit Rev Food Sci Nutr. 2014;54(6):734770. doi:10.1080/10408398.2011.606928

24. Lyons MM, Yu C, Toma RB, et al. Resveratrol in raw and baked blueberries and bilberries. J Agric Food Chem. 2003;51(20):58675870. doi:10.1021/jf034150f

25. Sanders TH, McMichael RW Jr, Hendrix KW. Occurrence of resveratrol in edible peanuts. J Agric Food Chem. 2000;48(4):12431246. doi:10.1021/jf990737b

26. Shi J, Zeng Q, Liu Y, Pan Z. Alternaria sp. MG1, a resveratrol-producing fungus: isolation, identification, and optimal cultivation conditions for resveratrol production. Appl Microbiol Biotechnol. 2012;95(2):369379. doi:10.1007/s00253-012-4045-9

27. Chen X, He H, Wang G, et al. Stereospecific determination of cis- and trans-resveratrol in rat plasma by HPLC: application to pharmacokinetic studies. Biomed Chromatogr. 2007;21(3):257265. doi:10.1002/bmc.747

28. Camont L, Cottart CH, Rhayem Y, et al. Simple spectrophotometric assessment of the trans-/cis-resveratrol ratio in aqueous solutions. Anal Chim Acta. 2009;634(1):121128. doi:10.1016/j.aca.2008.12.003

29. Salehi B, Mishra AP, Nigam M, et al. Resveratrol: a double-edged sword in health benefits. Biomedicines. 2018;6(3). doi:10.3390/biomedicines6030091

30. Caruso F, Tanski J, Villegas-Estrada A, Rossi M. Structural basis for antioxidant activity of trans-resveratrol: ab initio calculations and crystal and molecular structure. J Agric Food Chem. 2004;52(24):72797285. doi:10.1021/jf048794e

31. Ovesn Z, Horvthov-Kozics K. Structure-activity relationship of trans-resveratrol and its analogues. Neoplasma. 2005;52(6):450455.

32. Carter LG, DOrazio JA, Pearson KJ. Resveratrol and cancer: focus on in vivo evidence. Endocr Relat Cancer. 2014;21(3):R209R225. doi:10.1530/erc-13-0171

33. Zaffaroni N, Beretta GL. Resveratrol and prostate cancer: the power of phytochemicals. Curr Med Chem. 2021;28(24):48454862. doi:10.2174/0929867328666201228124038

34. Vernousfaderani EK, Akhtari N, Rezaei S, et al. Resveratrol and colorectal cancer: a molecular approach to clinical researches. Curr Top Med Chem. 2021;21(29):26342646. doi:10.2174/1568026621666211105093658

35. Sun X, Fu P, Xie L, et al. Resveratrol inhibits the progression of cervical cancer by suppressing the transcription and expression of HPV E6 and E7 genes. Int J Mol Med. 2021;47(1):335345. doi:10.3892/ijmm.2020.4789

36. Wu JM, Hsieh TC. Resveratrol: a cardioprotective substance. Ann N Y Acad Sci. 2011;1215:1621. doi:10.1111/j.1749-6632.2010.05854.x

37. Tan CS, Loh YC, Tew WY, Yam MF. Vasorelaxant effect of 3,5,4-trihydroxy-trans-stilbene (resveratrol) and its underlying mechanism. Inflammopharmacology. 2020;28(4):869875. doi:10.1007/s10787-019-00682-6

38. Rocha-Gonzlez HI, Ambriz-Tututi M, Granados-Soto V. Resveratrol: a natural compound with pharmacological potential in neurodegenerative diseases. CNS Neurosci Ther. 2008;14(3):234247. doi:10.1111/j.1755-5949.2008.00045.x

39. Amaya SC, Savaris RF, Filipovic CJ, et al. Resveratrol and endometrium: a closer look at an active ingredient of red wine using in vivo and in vitro models. Reprod Sci. 2014;21(11):13621369. doi:10.1177/1933719114525271

40. Saliba C, Jaafoury H, El Hajj M, Nicolas G, Haidar Ahmad H. Abdominal wall endometriosis: a case report. Cureus. 2019;11(2):e4061. doi:10.7759/cureus.4061

41. Jana V, Klani T, Pui M, et al. Proteomic analysis of peritoneal fluid identified COMP and TGFBI as new candidate biomarkers for endometriosis. Sci Rep. 2021;11(1):20870. doi:10.1038/s41598-021-00299-2

42. Jiang L, Wan Y, Feng Z, et al. Long noncoding RNA UCA1 is related to autophagy and apoptosis in endometrial stromal cells. Front Oncol. 2020;10:618472. doi:10.3389/fonc.2020.618472

43. Azam INA, Wahab NA, Mokhtar MH, Shafiee MN, Mokhtar NM. Roles of microRNAs in regulating apoptosis in the pathogenesis of endometriosis. Life. 2022;12(9):1321. doi:10.3390/life12091321

44. Yerlikaya G, Balendran S, Prstling K, et al. Comprehensive study of angiogenic factors in women with endometriosis compared to women without endometriosis. Eur J Obstet Gynecol Reprod Biol. 2016;204:8898. doi:10.1016/j.ejogrb.2016.07.500

45. Ahn SH, Monsanto SP, Miller C, Singh SS, Thomas R, Tayade C. Pathophysiology and immune dysfunction in endometriosis. Biomed Res Int. 2015;2015:795976. doi:10.1155/2015/795976

46. Filip L, Duic F, Prdatu A, et al. Endometriosis associated infertility: a critical review and analysis on etiopathogenesis and therapeutic approaches. Medicina. 2020;56(9):460. doi:10.3390/medicina56090460

47. Clower L, Fleshman T, Geldenhuys WJ, Santanam N. Targeting oxidative stress involved in endometriosis and its pain. Biomolecules. 2022;12(8):1055. doi:10.3390/biom12081055

48. Till SR, Nakamura R, Schrepf A, As-Sanie S. Approach to diagnosis and management of chronic pelvic pain in women: incorporating chronic overlapping pain conditions in assessment and management. Obstet Gynecol Clin North Am. 2022;49(2):219239. doi:10.1016/j.ogc.2022.02.006

49. Crain DA, Janssen SJ, Edwards TM, et al. Female reproductive disorders: the roles of endocrine-disrupting compounds and developmental timing. Fertil Steril. 2008;90(4):911940. doi:10.1016/j.fertnstert.2008.08.067

50. Sophonsritsuk A, Tantanavipas S, Tingthanatikul Y, Lertvikool S, Dittharot K, Waiyaput W. Effects of ethinyl estradiol in combined oral contraceptives on cell proliferation and apoptosis in ectopic endometrial tissue: a randomized controlled study. J Fam Reprod Health. 2021;15(1):4552. doi:10.18502/jfrh.v15i1.6077

51. Bruner-Tran KL, Osteen KG, Taylor HS, Sokalska A, Haines K, Duleba AJ. Resveratrol inhibits development of experimental endometriosis in vivo and reduces endometrial stromal cell invasiveness in vitro. Biol Reprod. 2011;84(1):106112. doi:10.1095/biolreprod.110.086744

Originally posted here:
Therapeutic effects and molecular mechanisms of resveratrol | IJWH - Dove Medical Press

Future Market Insights Global and Consulting Pvt. Ltd.

According to Future Market Insights, the North American region is forecast to lead the resveratrol market in 2023 and is likely do so throughout the forecast period. United States is a promising market in this region, which was estimated to have acquired 17.3% market share in 2022.

NEWARK, Del, May 09, 2023 (GLOBE NEWSWIRE) -- The estimated worth of the worldwide resveratrol market in 2022 was US$ 118.60 Million. Sales of dietary supplements is likely to increase to US$ 278.3 Million by 2033 thanks to shifting customer tastes, with a CAGR of 8% predicted for the forecast period of 2023 to 2033.

The growing demand for nutritional supplements among consumers is one of the main factors driving up the price of resveratrol on the international market. The market is expected to grow due to the product's high anti-antioxidant content and phenolic activities, which are popular with older consumers and sportsmen, as well as the increased prevalence of health issues including cardiovascular diseases. The increasing usage of nutraceuticals by the populace and the increasing reliance of the beauty sector on resveratrol all have an effect on the market's growth.

Download In-depth Report Sample @https://www.futuremarketinsights.com/reports/sample/rep-gb-2744

The use of this substance has been associated with a wide range of implications, including anti-angiogenic, estrogen-like effects, skin-whitening, anti-aging, collagen I activation, and its capacity to protect cells from oxidative damage and UV radiations-mediated cell death. It is well-liked in dermatology as well as cosmetology due to its ability to penetrate the skin barrier and its anti-aging properties.

Resveratrol has experienced extraordinary penetration in developed North American economies due to growing consumer demand for natural and healthy products. Consumers are turning to resveratrol supplementation for its antioxidant as well as anti-inflammatory qualities. Cardiovascular issues have increased in frequency in the United States as a result of the people's sedentary lifestyles, poor eating patterns, and hectic schedules. Resveratrol is a common ingredient in dietary supplements, which is anticipated to fuel the growth of the resveratrol market over the forecasted time period due to its multiple health benefits.

Story continues

Key Takeaways:

The global resveratrol market is expected to be valued at US$ 123 Million by 2023.

From 2018 to 2022, the market demand expanded at a CAGR of 3.1%.

In 2022, the United States market for resveratrol accounted for about 17.3% of the global market share.

The Indian resveratrol market to experience a rapid CAGR of 14% from 2023 to 2033.

By product type, the extract or plant-based resveratrol was estimated to acquire more than 40% share in 2022.

By Isomer, the trans-resveratrol had acquired a market share of 87%.

Resveratrol is gaining traction owing to its health benefits and having antioxidant, anti-inflammatory and anti-aging properties, says an analyst at FMI.

Competitive Landscape:

Prominent players in the resveratrol market are:

DSM Nutritionals

Evolva

Endurance Product Company

Great Forest Biomedical

Laurus Labs Limited

JF-NATURAL

Sabinsa Corporation

Resvitale LLC

Shanghai Natural Bio-engineering Co., Ltd.

Some key developments in this market are:

In 2021, Lonza, a worldwide manufacturing partner to the pharmaceutical, biotechnology, and nutrition sectors, declared it is likely to invest to build its production capabilities for pharmaceutical products at its facility in Guangzhou, China.

The fill as well as finish production line is likely to provide clinical trial and commercialization batches in China as well as local and international clients. In keeping with Lonza's objective to provide clients integrated end-to-end solutions, the launch of drug product manufacturing at the Guangzhou (CN) facility is likely to provide customers with a unified drug substance as well as drug product manufacturing service option.

More Valuable Insights Available:

Future Market Insights offers an unbiased analysis of the global resveratrol market, providing historical data for 2018 to 2022 and forecast statistics from 2023 to 2033.

To understand opportunities in the resveratrol market, the market is segmented on the basis of resveratrol by product (extract, fermentation, synthetic), form (powder and liquid), isomer (trans-resveratrol and cis-resveratrol), end-use and across five major regions (North America, Latin America, Europe, Asia Pacific and Middle East & Africa).

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Key Segments Profiled:

By Product:

Extract

Fermentation

Synthetic

By Form:

By Isomer:

Trans-Resveratrol

Cis-Resveratrol

By End Use:

Skin Care

Cream & Lotion

Scrub Exfoliator

Cleanser & Toner

Balm & Butter

Serum & Mask

Makeup Remover

Others

Hair Care

Shampoo

Conditioner

Essential Oil

Hair Color

Hair Stylist Products

Hair Oil

Makeup

Facial Makeup

Eye Makeup

Lip Makeup

Nail Makeup

Bath Care

Shower Products

Liquid Bath Products

Bath Additives

Bar Soaps

Fragrance

Tools

Dietary Supplements

Pharmaceuticals

Others

Table of Content (ToC):

1. Executive Summary | Resveratrol Market

1.1. Global Market Outlook

1.2. Demand-side Trends

1.3. Supply-side Trends

1.4. Technology Roadmap Analysis

1.5. Analysis and Recommendations

2. Market Overview

2.1. Market Coverage / Taxonomy

2.2. Market Definition / Scope / Limitations

3. Market Background

3.1. Market Dynamics

3.1.1. Drivers

3.1.2. Restraints

3.1.3. Opportunity

3.1.4. Trends

3.2. Scenario Forecast

3.2.1. Demand in Optimistic Scenario

3.2.2. Demand in Likely Scenario

3.2.3. Demand in Conservative Scenario

3.3. Opportunity Map Analysis

3.4. Product Life Cycle Analysis

3.5. Supply Chain Analysis

3.5.1. Supply Side Participants and their Roles

3.5.1.1. Producers

3.5.1.2. Mid-Level Participants (Traders/ Agents/ Brokers)

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Global Resveratrol Market is projected to reach US$ 278.3 Million by 2033 at a moderate CAGR of 8% | Get In-depth Report by Future Market Insights,...

When you think of ingredients in skin careeye creams in particularyou likely think of plumping and hydrating hyaluronic acid, de-puffing caffeine, line-smoothing retinol, and darkness-diminishing vitamin C. What you likely dont think of is a literally out-of-this-world ingredient researched on the exterior of The International Space Station. Alas, here in 2023, were learning to never be surprised, so when we caught wind of the new Delavie Sciences Aeonia Eye Refresh ($75)not to mention the news that it sold out within three hours of launchwe knew we needed to learn more.

Delavie Sciences, Aeonia Eye Refresh $75.00

Aeonia Eye Refresh is formulated with some of your typical eye cream ingredients, including caffeine, dimethicone, shea butter, and a number of UV-fighting antioxidants.

Caffeine constricts blood vessels reducing redness and leading to a tighter appearance of skin around the eyesits one of my top ingredients in an eye cream, says Claire Wolinsky, MD, a board-certified dermatologist and clinical instructor of dermatology at Mount Sinai School of Medicine.

Meanwhile, she says that as dimethicone and shea butter hydrate the delicate skin surrounding the eyes, effectively plumping the area and minimizing the appearance of fine lines, ferulic acid and resveratrol help protect skin against environmental damage and work to help reduce darkness and repair past photodamage.

The cream also contains polyglutamic acid, which Wolinsky says works as a humectant to draw water into the skin to provide hydration and prevent water loss. Additionally, its infused with hepta peptide 7, which is a peptide thats said to help support and stimulate collagen production, Wolinsky points out.

As beneficial as all of these ingredients can be, theyre not the stars of Aeonia Eye RefreshBacillus Lysate is.

According to SpaceFoundation.org, Bacillus Lysate is a commercial ingredient for UV protection in personal care products. Using a unique biological isolate, obtained from a national space exploration agency, Delavie Sciences has developed an ingredient that demonstrates significant UV absorption profiles, the site reads. Researched on the exterior of The International Space Station, Delavie Sciences enhanced the efficacy of the isolate by an average of 50 percent and 40 percent respectively against UVA and UVB.

With this new powerhouse ingredient for photoaging under its belt, Delavie Sciences aims to launch a number of UV-fighting productsAeonia Eye Refresh was among the first two and it was met with huge success, selling out within just three hours of launch.

Luckily for us, we were sent a sample to test and had the privilege of checking out this star-bound eye cream firsthand. While the cream looks and feels much like any other eye cream when squeezed out of the tube, we found that it does work especially well to hydrate, plump, and review tired-looking under-eyes. I used it after getting just five hours of sleep and you would have never guessed how sleep-deprived I felt.

That said, Ive only used the product for the past week, so Ive not noticed any long-term benefitsyet. Still, considering it doesnt pill over moisturizer or under SPFand since its quite soothing to apply thanks to the innovative metal massage tipits earned a spot in my daily line-up, and Im hopeful that it keeps me looking bright-eyed for the longhaul. After all, as board-certified dermatologist and founder of Russak Dermatology Clinic, Julie Russak, MD, sees it, in combination, the ingredients in this eye cream help to protect the skin from environmental stressors and improve its overall health. Sounds good to me!

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This Space Certified Eye Cream Sold Out in 3 Hours, and After It Made Me Look Well-Rested on 5 Hours of Sleep, I Can See Why - Well+Good

Its hard to beat the nostalgia and simplicity of a classic peanut butter and jelly sandwichwhatever your age may be. But as more schools and facilities are cracking down on allergens and other nuts are enjoying their 15 minutes of health fame, the humble peanut has been somewhat left behind.

It may surprise you that the peanut is actually not a nut at all. Rather, its a legume, sitting alongside lentils, peas, and beans. Also called groundnuts, historical evidence shows that peanuts have been used in culinary pursuits for nearly 3,500 years, and for good reason: They provide us with a wide variety of nutrients and healthy plant compounds. This nutritional value translates into bigtime health benefits for you and your loved ones, which youll find ahead.

In the macronutrient department, peanuts deliver in all three major groupsprotein, fat, and carbohydrates. Peanuts are a great source of protein, making them a frequent addition to plant-based dishes. In fact, the peanut contains more protein than any other kind of nut (even though its not technically a nut). Its versatility as both a sweet and savory ingredient lends itself to so many dishes, helping you to boost the protein content and energy-boosting power of your meals easily. (And ICYMI, protein also helps us to build and maintain our muscle mass while speeding recovery after injury and exercise.)

The peanut contains more protein than any other kind of nut (even though its not technically a nut).

Peanuts are also high in healthy fats, particularly monounsaturated fats. Monounsaturated fats, which are also found in olives, almonds, and avocados, have been linked with reduced inflammation, improved cholesterol levels, and may help reduce your risk of heart disease. These healthy fats will also help to stabilize our blood sugars after eating, avoiding the drastic spikes and crashes that really mess with our energy levels throughout the day and make managing blood sugar levels difficult for those with diabetes.

Finally, peanuts are also loaded with the complex carbohydrate, fiberparticularly insoluble fiber. To backtrack a bit, know that fiber is broken down into two main kinds: soluble and insoluble. Soluble fiber dissolves in water, creating a gel that can help reduce cholesterol and aid in digestive issues like diarrhea. Whereas, insoluble fiber does not dissolve in water and can promote overall gut health and regularity, especially for those who are struggling with constipation.

Its also worth noting that all three macronutrients found in peanuts will help you feel fuller longer as they take longer to digest and metabolize, equating to more satisfaction and energy for you.

When it comes to micronutrients, these legumes are loaded. Looking at vitamins, peanuts contain high levels of four of the eight B vitamins, including folate, thiamin, niacin, and biotin. While each B vitamin has unique health benefits, generally you can expect them all to help with healthy growth, development, energy metabolism, brain function, and overall cell health. Peanuts are also packed with vitamin E, a potent antioxidant that helps to reduce inflammation in the body, reducing the risk of chronic illness like heart disease and cancer.

In the mineral department, peanuts are an excellent source of manganese, with one cup providing over 150 percent of your daily needs. Manganese is vital for proper bone, connective tissue, blood, and hormone formation while also aiding in the metabolism of carbohydrates and the absorption of calcium. Peanuts are also high in magnesium, which is super important for muscle, nerve, and bone function as well as energy production in the body. Finally, you can also take big strides toward your daily phosphorus needs with peanuts. Phosphorus plays a large role in healthy bone and cell growth, repair, and maintenance as well as metabolism and absorption of both macro and micronutrients.

We cant forget about the ever important plant compounds that peanuts also offer, most notably resveratrol, phytosterols, and isoflavones. Resveratrol has been found to have staggering anti-inflammatory, anticancer, cardioprotective, neuroprotective, immune boosting, and antihypertensive benefits. Phytosterols, also known as plant sterols, are an umbrella term for over 200 different plant compounds, but as a group they are linked to having powerful cholesterol-lowering and anti-inflammatory properties. Isoflavones are part of the flavonoid group of phytonutrients, or plant compounds, that have (again) been shown to have antioxidant, anti-inflammatory, antimicrobial, and anticancer characteristics.

Research exploring the effects peanuts have on human health show super compelling findings. One meta-analysis found that peanut consumption was linked with improved HDL, or high density lipoprotein, cholesterol. This kind of cholesterol is considered the good type thats tied to improved heart health outcomes.

Another study, though much smaller, found that eating only one ounce of peanuts per day increased the number of healthy bacteria in the gut microbiome. The specific group of bacteria in question, called Ruminococcaceae, is linked not only to healthy digestion and regularity, but to improved liver metabolism and overall immune function. A final study looked at specific types of cancer affected by peanut intake. It found that increasing intake by only a small handful per day was linked with an eight percent risk reduction for colon, pancreatic, and overall cancer risk. It also showed that a small handful of all nuts (including peanuts) per day was associated with a four percent lower cancer mortality risk.

Another bonus reason to love peanuts: They have a much lower environmental impact compared to other nuts (again, even though theyre legume). To grow one ounce of peanuts requires 3.2 gallons of water. Comparatively, to grow the same amount of almonds uses 28.7 gallons of water, pistachios 23.6 gallons, and walnuts 26.7 gallons. Plus, peanuts are infamously used by farmers as nitrogen fixers, meaning that they convert nitrogen from the air into the soil. Fertilizers are usually primarily made up of nitrogen as its a main driver of plant health and growth. So, essentially peanut production can not only benefit our health, but the health of our soils and greater environment.

Another bonus reason to love peanuts: They have a much lower environmental impact compared to other nuts.

There are so many delicious ways to include more peanuts into your life. If savory foods are your jam, try making pad thai, refreshing spring rolls with a spicy peanut sauce, garlic green beans tossed with peanuts, or mouthwatering chicken satay.

When it comes to sweets, nothing beats a peanut butter banana smoothie, peanut butter overnight oats, or energy balls filled with nuts, seeds, whole grains, and peanut butter. A handful of peanuts on the go will also do the trick.

When shopping for peanuts and peanut butter, be sure to look for dry roasted peanuts, ideally unsalted and try to find peanut butters with as few added ingredients as possible.

Read more here:
Im an RDHeres Why Peanuts Are One of the Most Heart-Healthy Sources of Plant-Based Protein - Well+Good

Here is a whistle-stop tour of some of the innovations which exemplify these themes.

"Instagrammable" capsules:

Lonza provided a fun twist on capsule formats with capsugel liquid-filled capsules.The duocap capsule-in-capsule, means that the outer capsule can

be liquid or semi-solid, and the inner capsule can contain liquid, semi-solids, powder or beadlets.Joris Dewit, Executive Director and Head of Dosage Form Solutions and Ingredients at Lonza, said: Theyre intagrammable, can combine incompatible ingredients, and can come in many bespoke profiles.

Chewing gum to cut cravings:

Israeli startup Sweet Victory presented in the Startup Innovation Challenge introducing GymnemaSylvestre extract in chewing gum format. With itsglucose like moleculesit works to block sugar receptors to curb cravings. The founders claim consumers need only chew on one piece of gum for a few minutes to reduce sugar cravings.

Coffee gummies:

And for those needing a pep-up, Israeli company TopGum has released high caffeine 'cappuccino gummies'.In addition to providing the full coffee sensory experience, TopGum's gummies deliver a functional dose of caffeine: Each serving of two coffee gummies contains 40 mg of caffeine, which is equivalent to a standard espresso shot.Eli Edri, TopGum's COO and VP of strategic partnerships said: "Over the last couple of years, we worked on the development of a state-of-the-art microencapsulation technology called TopCaps that is uniquely tailored for gummies. This innovative technology allows consumers to savour the flavour and aroma of coffee-on-the-go, while energising themselves with a single chewy treat."

Marshmallow collagen:

EssentiaProtein Solutions showcased its Omnicol bovine collagen peptides in a marshmallow from. They note the concept is a nearly fat free treat providing 19 grams of collagen per 100 grams.

Calming gummies:

Herbaland calm & chill gummies for kids includeMagnesium and Chamomile Extract andpromise to help relieve restlessness and nervousness andrelieve inflammatory conditions of the gastrointestinal tract.Consumers are directed to take two of the strawberry flavour gummies per day to add a little 'calm to their day'.

Meanwhile Finzelberg showcased their Concental gummies. Utilising the company's Sideritis scardicaGreek tea extract, the gummies provide a tasty solution for increasing attention and reducing anxiety levels via the regulation of blood flow in the brain.

And Kerry created lemongrass-flavoured gummies with the firm's Sensoril Ashwagandha ingredient for a stress-relieving tasty supplement solution.

Chill out chocolate:

Providing an indulgent solution with calming benefits, Prinova developed a high protein plant-based recovery hot chocolate concept, including AlphaTea, the firm's branded L-Theanine sourced from green tea extract, shown to reduce stress and anxiety levels.

Resveratrol:

Resveratrol has been found to improve brain functionality through SIRT1 activation and inflammation modulation, prevention of oxidative stress, and via regulation of some signalling pathways. This ingredient was spotlighted at many stands including Veri-te, where the team showcased a range of food and drink formats, including chocolate truffles.

Gut-Brain:

NovozymesOneHealth showcased its ProbioBrain ingredient, a probiotic for mental wellness featuringBifidobacterium longum1714, targeting the gut-brain axis.Manel Berga, head of sales operations, told NutraIngredients: Sleep, mood, and stress are of particular interest to us. And we see that continuing togather interest in the industry. Brain health is a trend that is here to stay.

Low-stress sport:

Discussing the importance of adding additional functional benefits to protein powders, Fonterra highlighted its 'Nutiani Body + Brain'

range - in powder,drink and bar formats - offering protein alongside phospholipids to support cognition, focus and reduce stress. Alex Williams, marketing manager Europe, told NutraIngredients: "We are seeing other protein powders on the market with cognitive health benefits and they are performing very well but this is the first protein powder with phospholipids."

Gut-skin axis:

ADM brought its VitaSkin capsules to the show, formulated to target skin vitality, while also supporting the gut-skin axis using a blend of probiotics, zinc and vitamins A and C.

Nutraceutical gummies:

Sirio created gummy solutions for the beauty-from-within consumer withtwo new products. Its Jumping Jacks gummy is a type II collagen-powered sports nutrition gummy for joint health. Sirio partnered with Lonza for the inclusion of its patented UC-II collagen which is effective at just 40 mg per day and backed by 11 clinical trials. ItsPerfect Glow gummy is the "worlds first" full-spectrum (type I, II and III) collagen-based gummy for visible effects on skin elasticity, smoothness and glow.

Postbiotic gummies:

ADM concentrated on microbiome modulating solutions providing a range of scientifically backed benefits. Offering metabolic health benefits,ADMs apple and blackcurrant Bio Trinity Gummies featured a combination of fiber, plant extracts and vitamin E. And with a 'healthy living' focus,the firm showed its balanced wellness Red Beat Walk beverage concept supporting weight management, skin health, energy, immune function and metabolic health with probiotics, green tea extract, fiber, botanicals and vitamins B and D.

Carob prebiotics:

Foodtech startup Carobway joined the show to spotlight its potential in the prebiotic space.One formulation under development is a prebiotic powder enriched with fibers and polyphenols that possess anti-inflammatory properties and support a healthy gut microbiome. Following bioavailability and bio-accessibility studies, the start-up will advance a series of microbiome studies to explore the effect of its prebiotic on human microbiota diversity and specificmicrobes.

Menopause gummies:

A number of exhibitors showed awareness of the growing interest in menopause supporting solutions, ncluding HTC who showcased menopause gummies. The firm makes us of a range of hormone influencing ingredients including: starflower oil (aka borage oil) which is a rich source of gamma-linoleic acid (GLA); andEvening Primrose Oil, which is rich in omega-6and there is some evidence to suggest it could help relieve hot flashes and the symptoms of premenstrual syndrome (PMS).

Balancing botanicals:

Tilmans' brought its Pre-ms product to the show, combining evening primrose oil and lavender oil in capsule format to contribute to hormonal balance during the premenstrual period.

Hot flash relief treat:

Focusing ontheir Novasoy soy isoflavone concentrate, ADM produced a chocolate concept to deliver extracted genistein, an ingredient important for relief of hot flashes.

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Key themes from Vitafoods 2023 - NutraIngredients.com

Resveratrol is a plant compound derived from red grapes that has antioxidant-like properties. It is also present in products that are made from red grapes, such as wine and juice.

Many people use resveratrol as a health-boosting supplement. Research has linked the compound to potential health benefits such as improved brain health and blood pressure. It may also come with some side effects.

This article will explore the health benefits associated with resveratrol, side effects, when and how to consume it, and more.

Resveratrol is a compound that belongs to polyphenols stilbenoids group, consisting of two phenol rings that are connected by an ethylene bridge.

It is present in more than 70 plant species, primarily in the skin and seeds of red grapes. Resveratrol is also a phytoalexin, which is a protective antibiotic that plants produce under stress. Phytoalexin is what helps plants recover from fungal attacks, ultraviolet radiation, and other threatening circumstances.

When people consume reservatrol, it helps the body detoxify harmful molecules, much like antioxidants.

The human body metabolizes the compound quickly. It is fat-soluble and possesses anticarcinogenic, antioxidant, and estrogenic activity. Resveratrol is one of the main ingredients behind the health benefits of drinking red wine.

Learn more about the health benefits of red wine here.

There are many benefits associated with resveratrol, though they are mostly correlated to the compound rather than directly linked to the consumable supplement. A few of these health benefits include:

Research shows that resveratrol plays a role in protecting ovarian health, and in relieving poor pulmonary function. Resveratrol notably improves glucose homeostasis, providing insulin resistance by activating sirtuin, which regulates metabolism in insulin-target organs.

In addition, resveratrol may serve as a therapeutic agent for rheumatoid arthritis, as well as for male infertility and testicular malfunction.

More research is needed, as most of the above studies were animal studies. Human studies will help shed further light on resveratrols potential health benefits.

People use resveratrol for a number of other maladies, although there is even less research to support the compounds effectiveness for these ailments. These ailments include stomach aches, hepatitis, urinary tract infections, and fungal diseases. More research is needed to support these claims.

While there are comparably few side effects of resveratrol compared with the benefits, some studies show that it may behave as a pro-oxidizing agent in the body. Rather than consistently working to slow or prevent cell damage that free radicals cause, resveratrol may conversely exhibit pro-oxidant properties, leading to cellular DNA damage and oxidative stress.

Generally, if a person takes resveratrol in small quantities over the short term, they will not experience side effects. However, at doses of 2.5 grams (g) or more per day, the following side effects may occur:

Researchers conducting long-term clinical trials did not record any major side effects.

In research from 2016, one participant developed fever and bicytopenia (reduced blood cells) while receiving 1.5 g resveratrol per day for 6 months.

The easiest way to consume resveratrol in safe amounts is via grapes, wine, blueberries, cranberries, pomegranates, and juices that contain these fruits.

Some people also take resveratrol supplements, especially for lowering blood pressure. Many of these supplements contain much higher doses of resveratrol than a person would naturally consume in food sources.

The proper dosage of resveratrol is unclear and remains under debate by medical professionals.

Clinical trials show that it is technically safe to take resveratrol in doses of up to 5 g per day, though taking more than 2.5 g per day is likely to result in abdominal side effects, such as cramping, flatulence, nausea, and more.

Research from 2015 shows that doses of less than or equal to 0.15 mg of resveratrol may be most effective in reducing pressure on artery walls to better manage blood pressure.

Overall, people have different tolerances when it comes to resveratrol, and there is no specific dose that is recommended across the board. People should talk to their doctor about the dose that might be safest and most beneficial for their body.

Resveratrol is a naturally-occurring compound present in grapes, some berries, and other fruits and nuts.

It often mimics antioxidant activity in the body, and may provide many health benefits. Research most supports its use for cardiovascular protection and blood pressure regulation.

People may consume resveratrol through their dietary selections or via supplements. The recommended dose of resveratrol is not conclusive, but high quantities may lead to gastrointestinal upset.

A doctor, dietitian, or qualified medical professional may be helpful in determining what the best amount of resveratrol is for an individual.

More:
Resveratrol benefits, dosage, and more - Medical News Today

Resveratrol has been in the news on and off over the last few decades. Headlines have touted resveratrol in skin care, weight loss, heart health, and several other conditions. Its a naturally occurring compound called a polyphenol. You can find it in certain foods and as a resveratrol supplement. Heres what you need to know about resveratrol, including how to safely include it in your diet or start a resveratrol supplement regimen.

Resveratrolor trans-resveratrolis a chemical with antioxidant properties. Antioxidants help cells resist damage from unstable atoms called free radicals. Over 70 plant species have detectable levels of it, with Japanese knotweed having the highest content. Scientists believe plants make it to protect themselves against pathogens and natural radiation.

Several foods contain resveratrol, including grapes, blueberries, cranberries and peanuts. Red wine has the highest concentration of resveratrol for foods. This is thanks to the amount of time grape skins spend in fermentation to make red wine. Resveratrols presence in red wine is one reason you may have heard it touted as heart-healthy. It first started with the so-called French Paradoxthe low rate of heart disease in French people despite their high consumption of saturated fats. Red wine was at the center of explaining the paradox because the French consume a lot of it. When scientists started studying compounds in red wine, they found resveratrol.

Laboratory and animal studies have suggested several resveratrol benefits. Even human studies have shown positive results in certain markers of disease. However, there are few well-controlled human studies. And results havent been able to show clear-cut gains in health and survival, despite the changes in disease biomarkers. The list of potential resveratrol benefits includes:

More research is necessary before scientists can say for certain whether any of these resveratrol benefits are real or not.

People tend to think that natural means safe. People also tend to think over-the-counter products are generally safe. In fact, all drugs, including herbal or natural supplements, have potential safety issues. With resveratrol, some of its beneficial actions can also be problems in the wrong person.

People who should not take resveratrol include:

In general, resveratrol has few side effects. However, diarrhea and other digestive symptoms are possible at high doses.

As with any vitamin or natural product, the best place to get resveratrol is in your diet. It cant hurt to add foods that contain it to your diet. And if you already enjoy a glass of red wine, youre probably getting some resveratrol as a bonus.

If youre looking to add a resveratrol supplement, its best to talk with your doctor first. Make sure its potential biologic actions wont be harmful for you based on your medical history or the medications you take. Then, choose the right supplement.

Most resveratrol supplements contain some combination of extracts from grape seeds, red wine, berries, and Japanese knotweed. Japanese knotweed has the highest concentration in plants, so its often a first ingredient on the label. However, Japanese knotweed extracts also contain the chemical emodin, which can cause diarrhea. If you develop digestive upset with a resveratrol supplement, check to see if its from Japanese knotweed extract. Switching to a different resveratrol extract may help.

After verifying the ingredients, look for micronized resveratrol on the label. Resveratrol is hard for the body to absorb and use. Micronizing the compound makes it easier for your body to absorb and use it. Resveratrol liquid and patches are also available.

Keep in mind, the FDA (Food and Drug Administration) regulates supplements as foods, not drugs. Manufacturers dont have to provide the same purity, safety and efficacy proof that drug makers do. So, its important to do your homework. Buy a resveratrol supplement made by a reputable manufacturer.

Also, look for certification stamps on the label, but be careful. Some manufacturers put misleading stamps to make them look official. Reliable stamps include USP, CL and NSF. Manufacturers with these stamps have voluntarily had their products tested for purity. A stamp from one of these organizations validates the content claims on the label are true. These stamps arent an endorsement of safety or efficacy.

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When Should You Take Resveratrol? - Healthgrades

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Resveratrol is a class of plant micronutrients called polyphenols. Polyphenols are organic chemicals that plants make to survive drought or attack from disease. These compounds are found in plant foods and have a variety of health benefits.

Resveratrol is found in peanuts, berries, and grapes. It is also found in red wine in higher amounts. Resveratrol has antioxidant and anti-inflammatory properties to protect you against diseases like cancer, diabetes, and Alzheimers disease.

The anti-inflammatory effects of resveratrol make it a good remedy for arthritis, and skin inflammation. Also, resveratrol has antibacterial and antifungal properties that help treat infections of the urinary and digestive tracts.

Polyphenols like resveratrol are important to protect the body from free radical cellular damage. Free radicals form in the body naturally when your body breaks down food, you breathe in cigarette smoke, or if you are exposed to radiation. They are unstable and attack cells. They are also responsible for the development of some age-related diseases.

Resveratrol can prevent these common conditions:

Cancer

Many studies indicate that resveratrol could help prevent and treat certain types of cancer. Its anti-tumor effects include inhibiting cancer cell growth, cell signaling, angiogenesis, and promoting cell death.

Studies have found that resveratrol negatively affects cancer at all stages of development. Most importantly, researchers have found that resveratrol makes chemotherapy more effective by blocking chemotherapy-resistant proteins.

Cardiovascular Disease

Numerous studies have explored resveratrols role in preventing and managing cardiovascular (heart-related) disease. Resveratrol exhibits protective effects against blood vessel damage. Studies also show that it lowers cholesterol levels and prevents blood clots.

Many researchers have concluded that resveratrol is a valuable micronutrient that can prevent heart disease in those at risk and help treat people with progressing cardiovascular conditions.

Dementia and Alzheimers Disease

The anti-inflammatory properties of resveratrol are effective in controlling inflammation throughout the body, including the brain. Neuroinflammation (inflammation of parts of the nervous system) is one factor that contributes to the progression of brain-related problems, such as Alzheimers disease, dementia, and multiple sclerosis.

One study followed participants with Alzheimers disease for 52 weeks to observe the therapeutic effects of resveratrol. One control group received a placebo, while another received resveratrol. For the group with the placebo, neurological biomarkers continued to decline over the observational period. However, the group receiving daily doses of resveratrol saw stabilization in those same biomarkers.

While further study is needed, the outcome of this study seems promising for the use of resveratrol in the future.

Diabetes

Resveratrol has demonstrated health benefits for people with Type 2 diabetes in several studies. For example, researchers commonly see improvements in serum lipid (cholesterol) and glucose (sugar) levels after treating test subjects with resveratrol.

The studies show that resveratrol reverses insulin resistance, lowers blood sugar levels, and even lowers elevated blood pressure, a condition many people with diabetes have.

The amount of resveratrol naturally contained in foods is considered safe for daily consumption. Low to medium doses of resveratrol are considered safe, even when taken for long periods. Higher doses of up to 3,000 milligrams per day can be taken safely for up to six months, but some people have reported stomach upset.

You may want to avoid resveratrol supplements in these situations:

Bleeding Disorders

Resveratrol decreases blood clotting. If you have a blood clotting disorder and are at risk for bleeding, you should avoid taking resveratrol supplements.

Estrogen Sensitivity

Resveratrol can act like the hormone estrogen in the body. If you have an estrogen-sensitive condition like endometriosis, uterine fibroids, or reproductive cancers, do not take resveratrol.

Surgery

Due to resveratrols blood-thinning properties, you should stop taking any resveratrol supplements two weeks before surgery.

Medication Interactions

Resveratrol slows blood clotting. If taken with anticoagulant (non-clotting) medications, you are at increased risk of bleeding. Anticoagulants include warfarin, heparin, naproxen, ibuprofen, and aspirin.

Resveratrol occurs naturally in some plant foods. You can add resveratrol to your diet by eating foods like peanuts, grapes, blueberries, raspberries, and mulberries. Red wine is also a good source of resveratrol.

You can also find resveratrol supplements in the vitamin section of your grocery store. There is no recommended daily allowance for resveratrol. Supplements may contain 100 milligrams, 250 milligrams, or 500 milligrams of resveratrol per capsule.

SOURCES:

Annals of the New York Academy of Sciences: Resveratrol for Alzheimers disease.

Biomedicines: Resveratrol: A Double-Edged Sword in Health Benefits.

Endocrinology: Resveratrol Acts as a Mixed Agonist/Antagonist for Estrogen Receptors and .

Europe PMC: Advances in resveratrol studies.

Inflammation & Allergy-Drug Targets: Anti-Inflammatory Responses of Resveratrol.

Inflammation: Effects of Resveratrol in Inflammatory Arthritis.

International Journal of Antimicrobial Agents: Antibacterial and antifungal properties of resveratrol.

Mayo Clinic: Antioxidants.

Mayo Clinic: Red wine and resveratrol: Good for your heart?

Nutrition and Metabolism: Effects of resveratrol on glucose control and insulin sensitivity in subjects with type 2 diabetes: systematic review and meta-analysis.

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Resveratrol: Health Benefits, Safety Information, Dosage, and More - WebMD

Biomedicines. 2018 Sep; 6(3): 91.

1Medical Ethics and Law Research Center, Shahid Beheshti University of Medical Sciences, Tehran 88777539, Iran; moc.liamg@700ihelas.rahab

2Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran 22439789, Iran

3Department of Pharmaceutical Chemistry, H. N. B. Garhwal (A Central) University, Srinagar Garhwal 246174, Uttarakhand, India; moc.liamg@ugbnhmehcamrahpyahba

4Department of Biochemistry, H. N. B. Garhwal (A Central) University, Srinagar Garhwal 246174, Uttarakhand, India; ni.ca.ugbnh@magin.m

6Department of Medical Parasitology, Zabol University of Medical Sciences, Zabol 61663335, Iran

7Antimicrobial and Biocontrol Agents Unit, Department of Biochemistry, Faculty of Science, University of Yaounde 1, Ngoa Ekelle, Annex Fac. Sci, P.O. Box. 812, Yaounde-Cameroon

8Faculty of Medicine, University of Porto, Alameda Prof. Hernni Monteiro, Porto 4200-319, Portugal

9Institute for Research and Innovation in Health (i3S), University of Porto, Porto 4200-135, Portugal

10Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran 11369, Iran

11Department of Chemistry, Richardson College for the Environmental Science Complex, The University of Winnipeg, Winnipeg, MB R3B 2G3, Canada

2Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran 22439789, Iran

6Department of Medical Parasitology, Zabol University of Medical Sciences, Zabol 61663335, Iran

7Antimicrobial and Biocontrol Agents Unit, Department of Biochemistry, Faculty of Science, University of Yaounde 1, Ngoa Ekelle, Annex Fac. Sci, P.O. Box. 812, Yaounde-Cameroon

8Faculty of Medicine, University of Porto, Alameda Prof. Hernni Monteiro, Porto 4200-319, Portugal

9Institute for Research and Innovation in Health (i3S), University of Porto, Porto 4200-135, Portugal

10Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran 11369, Iran

11Department of Chemistry, Richardson College for the Environmental Science Complex, The University of Winnipeg, Winnipeg, MB R3B 2G3, Canada

Received 2018 Aug 14; Accepted 2018 Sep 7.

Resveratrol (3,5,4-trihydroxy-trans-stilbene) belongs to polyphenols stilbenoids group, possessing two phenol rings linked to each other by an ethylene bridge. This natural polyphenol has been detected in more than 70 plant species, especially in grapes skin and seeds, and was found in discrete amounts in red wines and various human foods. It is a phytoalexin that acts against pathogens, including bacteria and fungi. As a natural food ingredient, numerous studies have demonstrated that resveratrol possesses a very high antioxidant potential. Resveratrol also exhibit antitumor activity, and is considered a potential candidate for prevention and treatment of several types of cancer. Indeed, resveratrol anticancer properties have been confirmed by many in vitro and in vivo studies, which shows that resveratrol is able to inhibit all carcinogenesis stages (e.g., initiation, promotion and progression). Even more, other bioactive effects, namely as anti-inflammatory, anticarcinogenic, cardioprotective, vasorelaxant, phytoestrogenic and neuroprotective have also been reported. Nonetheless, resveratrol application is still being a major challenge for pharmaceutical industry, due to its poor solubility and bioavailability, as well as adverse effects. In this sense, this review summarized current data on resveratrol pharmacological effects.

Keywords: resveratrol, physiological effects, pharmacological activity, antioxidant, anticancer, antimicrobial

Among many phytochemicals, phytoestrogens have been reported to contain several bioactive molecules, mostly found in soy, vegetables and fruits. These compounds can be classified into four main groups, such as isoflavonoids, flavonoids, stilbenes and lignans. From them, stilbenes, in particular trans-resveratrol and its glucoside, are widely reported to be beneficial to human health, having even shown to possess antioxidant, anticarcinogenic, antitumor and estrogenic/antiestrogenic activity [1].

Specifically, resveratrol is well known biologically active compound synthesized by plants undergoing infectious or ionizing radiation. Renaud and De Lorgeril were the first to relate wine polyphenols such as resveratrol, to the potential health benefits attributed to regular and moderate wine consumption (the so called French Paradox) [2]. Resveratrol has since received an increasing scientific attention, leading to investigation on its biological activity, and to numerous publications [3]. Resveratrol was first isolated from white hellebore (Veratrum grandiflorum O. Loes) roots in 1940, then from Polygonum cuspidatum roots in 1963, a plant used in traditional Chinese and Japanese Medicine as anti-inflammatory and anti-platelet agent. This natural polyphenol has been detected in more than 70 plant species, and is also found in discrete amounts in red wines and various human foods. High concentrations are present in grapes, possibly because of Vitis vinifera response to fungal infection. In plants, resveratrol acts as a phytoalexin that is synthesized in response to mechanical injury, UV irradiation and fungal attacks. For industrial purposes, resveratrol is generally obtained by chemical or biotechnological synthesis from yeasts Saccharomyces cerevisiae [4,5,6,7,8].

As of today, 92 new resveratrol compounds, including 39 dimers, 23 trimers, 13 tetramers, 6 resveratrol monomers, 6 hexamers, 4 pentamers, and 1 octamer have been reported from the Dipterocarpaceae, Paeoniaceae, Vitaceae, Leguminosae, Gnetaceae, Cyperaceae, Polygonaceae Gramineae, and Poaceae families [9]. Among these families, Dipterocarpaceae, containing 50 resveratrols, accounts for the majority, being involved 7 Dipterocarpaceae genera, including Vatica, Vateria, Shorea, Hopea, Neobalanocarpus, Dipterocarpus and Dryobalanops [9]. Currently, resveratrol is sold as a nutritional supplement with a wide range of pharmacological effects, including cellular defensive action against oxidative stress [10,11,12]. In this sense, the present review summarizes resveratrol beneficial health effects, including anticancer, antimicrobial, neuroprotective, antiaging, anti-inflammatory, cardioprotective and blood-sugar lowering properties, as also life-prolonging effects.

Resveratrol is a stilbenoid polyphenol, possessing two phenol rings linked to each other by an ethylene bridge. The chemical structure of resveratrol (trans-3,5,4-trihydroxystilbene) is identified in two isomeric forms, cis- and trans-resveratrol (). trans form is dominant in terms of its prevalence and different biological activities are attributed, namely in inducing cellular responses such as cell cycle arrest, differentiation, apoptosis, and to enhance cancer cells anti-proliferation [13,14,15].

Resveratrol chemical structure (cis and trans forms).

Formal chemical name (IUPAC name) of resveratrol is E-5-(4-hydroxystyryl)benzene-1,3-diol. Various aspects on resveratrol chemistry are currently being studied. It exists as two geometric isomers: cis-(Z) and trans-(E). trans form can undergo to cis form isomerization when exposed to UV irradiation. trans-resveratrol powder was found to be stable under accelerated stability conditions of 75% humidity and 40 C in the presence of air. The low resveratrol bioavailability was encumbered its therapeutic application. Therefore, modification of resveratrol structure has received special attention from researchers and many resveratrol derivatives have been synthesized such as methoxylated, hydroxylated and halogenated derivatives, all of them exhibiting favorable therapeutic potential [3,16,17]. Resveratrol is present in dietary products as glycosylated forms, known as piceid. Though, plants and pathogens, and even human digestive tract possess enzymes able to triggers polyphenols oxidation (and subsequent inactivation), the glycosylation prevents enzymatic oxidation of resveratrol, thereby preserving its biological effects and increasing its overall stability and bioavailability [18]. Furthermore, since intestinal cells can absorb only resveratrol aglycone form, absorption process requires glycosidases. Therefore, the relative aglycone and glycosylated resveratrol amounts in foods and beverages may modulate its absorption rate [19].

Three glycosylated resveratrol analogues, piceid, piceatannol glucoside, and resveratroloside isolated from the invasive plant species Polygonum cuspidatum [19] were identified as the major antibacterial compounds [20]. Glycosylated resveratrol analogues have comparable biological effects after transepitelial passage, as they can be hydrolyzed into deglycosylated forms, resveratrol in the intestine [21]. However, in vitro studies have shown that the glycosylated analogues even show more powerful bioactivities. For example, resveratrol and piceid have similar antioxidant capacity, but piceid appears to be more efficacious than resveratrol due to its reaction with its radical form [22,23]. Indeed, resveratrol-glycoside was more effective than resveratrol against hepatitis B virus [24,25]. Piceatannol, with one more hydroxyl group, was already reported as having stronger anti-inflammatory, immunomodulatory, anti-proliferative, anti-leishmanial, anti-leukemic, and protein-tyrosine kinase inhibitory effects [19].

Pterostilbene, a natural methoxylated resveratrol analogue, was first isolated from Pterocarpus santalinus (red sandalwood), a plant used in traditional medicine for diabetes treatment [26]. This Pterocarpus marsupium active constituent is mainly found in blueberries, grapes, and several plant woods. [26,27]. Pterostilbene has a similar structure to resveratrol except that in A ring 3 and 5 position was replaced by a methoxyl group [26]. This compound pro-lipophilicity, greater than that of resveratrol, increases its bioavailability [28,29,30] resulting in stronger bioactivities, including anticancer, anti-lipidemic, antidiabetic, and cardioprotective effects than those of resveratrol [26,31,32].

In the same line, resveratrol nanoformulation have been conceived as a promising approach for biological function retaining, where polycaprolactone form the hydrophobic core, whereas polyethylene glycol form the hydrophilic shell of the encapsulated resveratrol micelles [33,34]. Solid lipid nanoparticles and nanostructured lipid carriers are two unique resveratrol nanodelivery systems that were developed to enhance resveratrol oral bioavailability for nutraceutical purposes [35]. Indeed, resveratrol nanoparticles led to an improvement in its solubility and enhances its antioxidant potential than free form [35,36]. For example, resveratrol nanoformulation exhibited an in vivo absorption raise, length of action extension and bioavailability improvement by 3.516 times more, when compared with raw form [37]. In addition, the hydrophobic nature of resveratrol considerably contributes to its limited bioavailability, which results from its poor water solubility. Thus, resveratrol encapsulated in methylated--cyclodextrins (in a ratio 1:1) improved its water solubility (about 400-fold), and consequently its bioavailability, maintaining its antioxidant and antibacterial effects (against Campylobacter) [38], at same time that encourages its further application in food industry, aiming at foodborne pathogens control, as well as for nutraceuticals purposes.

Resveratrol possesses a wide range of biological properties, among them antioxidant, cardioprotective, neuroprotective, anti-inflammatory and anticancer activities [19,38].

Resveratrol possess many biological properties, but the best described resveratrol property is their capacity to act as a potent antioxidant [39]. Resveratrol antioxidant activity depends upon the arrangement of functional groups on nuclear structure. Therefore, configuration, substitution, and total hydroxyl groups number substantially influence several mechanisms of antioxidant activity, such as radical scavenging and metal ion chelation abilities. Previous studies showed that hydroxyl group in 4 position is not the sole determinant for antioxidant activity, but also the 3- and 5-OH groups [40,41]. The study of antioxidant effect against hydroxyl (OH) and hydroperoxyl (OOH) radicals in aqueous simulated media using density functional quantum chemistry and computational kinetics methods revealed that trans-resveratrol may act as an efficient OOH, and also presumably OOR, radical scavenger [42]. Resveratrol can also be used in minimizing or preventing lipid oxidation in pharmaceutical products, delaying toxic oxidation products formation, and maintaining both nutritional quality and prolonging pharmaceuticals shelf-life [43,44,45]. In addition, resveratrols antioxidant properties have been successfully employed to protect cells against hydrogen peroxide-induced oxidative stress, where the pre-treatment with resveratrol promoted cell survival and protection against UV-irradiation-induced cell death. Resveratrol cellular defense could be achieved, at least in part, by its ability to act as a direct antioxidant and an indirect cellular antioxidant system inducer through modulation of several cellular antioxidant pathways, thereby balancing cellular redox status [10,46,47].

As already highlighted, resveratrol is a powerful antioxidant that beneficial effect is hampered by its low bioavailability. Many attempts have been made to generate resveratrol derivatives by esterification process to improve their lipophilicity and application in lipid-based foods and biological environments. About 12 different esterified acyl chlorides have been synthesized including butyryl chloride, caproyl chloride, capryloyl chloride, capryl chloride, docosahexaenoyl chloride, eicosapentaenoyl chloride, lauroyl chloride, myristoyl chloride, oleoyl chloride, palmitoyl chloride, propionyl chloride, and stearoyl chloride. These derivatives were able to effectively inhibit copper ion-induced low-density lipoprotein (LDL) oxidation and inhibited hydroxyl radical-induced DNA scission [33]. These results clearly demonstrated that resveratrol derivatives might serve as potential antioxidants in foods and biological systems.

Numerous studies have demonstrated that resveratrol possesses antitumor action and is a likely candidate for treatment and prevention several types of cancer [31,48]. The anticancer properties of resveratrol have been confirmed by many in vitro and in vivo studies, which show that resveratrol is able to inhibit all carcinogenesis stages (e.g., initiation, promotion and progression) [49,50,51]. Many studies also provided evidence that resveratrol not only acts a chemopreventive agent, but also display chemotherapeutic properties linked to its anti-inflammatory, antioxidant, pro-apoptosis and anti-proliferative actions [50,52]. Indeed, Resveratrol is believed to target intracellular signaling pathway components such as regulators of cell survival and apoptosis, pro-inflammatory mediators, and tumor angiogenic and metastatic switches by modulating a distinct set of transcription factors, upstream kinases, and their regulators [53]. For instance, resveratrol have demonstrated apoptotic and anti-proliferative effects on human cervical carcinoma by inducing cell shrinkage in HeLa cells and apoptosis through the activation of caspase-3 and -9, upregulation of the expression of the pro-apoptotic B-cell lymphoma (Bcl)-2-associated X protein and downregulation of the expression of the anti-apoptotic proteins Bcl-2 and Bcl-extra-large in HeLa cells, and increased expression of the p53, a protein that is essential for cell survival and cell cycle progression [54]. Cheng et al. demonstrate that resveratrol exert its anticancer action in in pancreatic cancer cells by suppressing the expression of NAF-1 through activation of Nrf2 signaling and inducing cellular reactive oxygen species accumulation that lead to apoptosis activation and prevent proliferation of pancreatic cancer cells [55]. Resveratrol is also an Histone deacetylase inhibitors that display its antiproliferative action by activating cell cycle arrest, inducing apoptosis and autophagy, angiogenesis inhibition, increasing reactive oxygen species generation causing oxidative stress, and mitotic cell death in cancer cells [56]. The presence of 4-OH together with the stereoisomer in trans-conformation (4-hydroxystyryl moiety) is absolutely required for cell proliferation inhibition [40]. Enzymatic assays demonstrated that DNA synthesis inhibition was induced by a direct interaction of resveratrol with DNA polymerases [40]. Another in vitro work has shown that resveratrol enhances chemotherapy effectiveness through inactivating NF-B protein (a transcription factor) formed by cancer cells and which controls certain genes expression. When this factor is present, cancer cells become chemotherapy-resistant, which then allows them to multiply. Resveratrol acts blocking this transcription factor, thereby enabling chemotherapeutics to act at their targeted sites [57,58,59]. Resveratrol also attenuates the acetylation, phosphorylation, and nuclear translocation of NF-B [60] and inhibit iNOS expression in colon cancer cells (a key enzyme in colon tumorigenesis induced by pro-inflammatory and cytokines agents) and the IGF-1R/Akt/Wnt pathways, and activates p53 to hampered cell and tumor development [60]. These effects fall into two classes: (i) Well-documented anti-proliferative and pro-apoptotic effects on cancer cell lines; and (ii) slightly more hypothetical chemopreventive effects that corresponds to resveratrol effects on cancer initiation [57,58,59].

Besides, the phytoestrogen, resveratrolt has received great attention as an upcoming preventive and therapeutic agent against breast cancer [61]. Resveratrol has also shown promise as part of combination therapy, particularly in breast cancer [62]. This compound has been shown to reverse drug resistance in a wide variety of in vitro cell systems by sensitizing tumor cells to drug-mediated effects in combination with other chemotherapeutic agents [50]. Resveratrol demonstrates ability to enhance the sensitivity of pancreatic cancer cells to gemcitabine therapy [55]. Cisplatin, a cancer chemotherapy agent against ovarian, bladder, testicular, and many other cancers, high risk of nephrotoxicity is reduce by Resveratrol [63]. Globally, many in vitro and animal-based studies have demonstrated such preventive anticancer activity in colon, cervical, prostate, breast and lungs [50,64,65,66,67,68,69]. Resveratrol-loaded nanoparticles have also demonstrated antioxidant potential in cancer cells [37]. In addition, resveratrol beneficial effects are also present when adopted as a conventional treatment support to cancer, using chemotherapy and radiotherapy [70,71,72]. Based on previous experimental and clinical trials, and on molecular characteristics of resveratrol, it could be used as: (i) A neoadjuvant chemotherapy agent before surgery to decrease tumor volume, owing to its ability to inhibit cancer cell proliferation and to induce apoptosis; (ii) an adjuvant chemotherapy drug to inhibit early cancer invasion and metastasis after surgery; (iii) a radiotherapy or chemotherapy sensitization agent in combination with chemotherapy agents, like capsaicin, docetaxel, doxorubicin, gemcitabine and temozolomide, since resveratrol may improve their anticancer effects; (iv) in cancer prevention for people under high risk of cancer; (v) a radioprotective agent to reduce treatment adverse effects, including radiotherapy-induced xerostomia and mucositis.

Resveratrol protective effect was shown to improve cardiovascular function in diabetic rats [73,74] by preserving the functional abilities of cardiac stem/progenitor cell compartments and mature cardiac cells, improved cardiac environment by reducing inflammatory state and decreased unfavorable ventricular remodeling of the diabetic heart, leading to a marked recovery of ventricular function [74]. Resveratrol showed beneficial effect in heart failure by improving left ventricle function, decreased cardiac hypertrophy, contractile dysfunction and remodeling, interstitial fibrosis, and the level of plasma BNP [75]. Some molecular mechanism of resveratrol action include inhibition of prohypertrophic signaling molecules, improvement of myocardial Ca2+ handling, phosphorylation of prosurvival (Akt-1, GSK-3) and stress signaling (MKP-1) pathways and the reduction of oxidative stress and inflammation (iNOS, COX-2 activity, and ROS formation) [75]. Yan et al. suggest that resveratrol act by preventing the expressions of endothelial nitric oxide synthase, vascular endothelial growth factor, and suppressing phosphorylation of p38 in rats with diabetes-related myocardial infarction [73]. Besides, resveratrol administration in myocardial infarction-related diabetic rats significantly reduced blood glucose, body weight, plasma triglyceride levels, heart rate and aspartate transaminase (AST)/alanine transaminase (ALT) ratio, at same time that markedly increased total plasma insulin levels [73,76]. In addition, resveratrol significantly reduced inflammation factors and malondialdehyde levels, which is a marker of oxidative stress [77]. These results showed that resveratrol treatment can improve cardiovascular function by reducing myocardial ischemia-reperfusion injury, vasodilation and atherosclerosis [78]. Contrarily, at physiological concentrations, resveratrol induces vasodilation, and consequently decreases hypertension and cardiovascular diseases risk [79]. On the other hand, these results have also confirmed the uses of Polygonum cuspidatum as a resveratrol source to treat and to prevent hyperlipidemia and arteriosclerosis in traditional chinese medicine [80,81,82]. Overall, the cardiovascular protective effect of resveratrol have been linked to multiple molecular targets and might be useful to the development of novel therapy for atherosclerosis, metabolic syndrome, ischemia/reperfusion, and heart failure [83].

Resveratrol has several neuroprotective roles in various neurodegenerative impairments, such as Alzheimers, Huntingtons and Parkinsons diseases, amyotrophic lateral sclerosis and alcohol-induced neurodegenerative disorders [84,85]. It has been shown that resveratrol protective effects are not limited to the anti-inflammatory and antioxidant activity but also improved mitochondrial functions and biogenesis through SIRT1(sirtuin 1)/AMPK/PGC1 pathway and vitagenes, which prevent the deleterious effects triggered by oxidative stress [85,86,87]. Resveratrol decreases cholinergic neurotransmission, brain-derived neurotrophic factor expression, and oxidative stress, promotes -amyloid peptides clearance and anti-amyloidogenic cleavage of APP, and reduces neuronal apoptosis [88]. A meta-analysis showed that resveratrol significantly decreased Profile of Mood States (POMS) including vigor and fatigue but had no significant effect on memory and cognitive performance [89]. Among the isolated resveratrol oligomers, vitisin A and heyneanol A have been reported for better dose-dependent inhibitory potential compared with standard inhibitor (galantamine) on both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity [17,37]. Resveratrol is also able to improve rat motor abilities and to deactivate neuroinflammatory response following intracerebral hemorrhage. It may be used as a novel therapeutic agent to treat intracerebral hemorrhage [90,91].

Stilbenoids including resveratrol are non-nitrogenous polyphenols with acidic and amphiphilic characters with anti-inflammatory activity. Many of their targets are occurring on cyclooxygenase (COX), 5-lipoxygenase (5-LOX) and protein kinase B [92], which is associated with its ability to inhibit COX-1 and COX-2 activity along with transcription factors activity inhibition, directly involved in COX activity regulation [93]. Studies reported the ability of resveratrol to reduce the secretion and expression of inflammatory factors [94]. The anti-inflammatory activity of resveratrol prevents acute pharyngitis-induced inflammation by inhibiting NF-B, tumor necrosis factor- and interleukin-6 serum levels, macrophage inflammatory protein-2 and cyclooxygenase-2 activity levels, reactive oxygen species production and caspase-3/9 in rabbit models [94]. Resveratrol inhibit the ear oedema of mice, WBC and pleurisy exudates, decrease the production of NO, and elevate the activity of SOD in serum in acetic acid-induced pleurisy test, reduce the content of MDA and elevate the T-SOD activity in serum; RSV could inhibit the expressions of TP, PGE2, NO, and MDA in carrageenan-induced synovitis test supporting its analgesic and anti-inflammatory activities [95]. Resveratrol inhibit the activation of microglia that lead to the release of various pro-inflammatory factors, the production of reactive oxygen species, and the activation of signal pathways leading to neuroinflammation [96] in in vitro resveratrol modulates the inflammatory response at moderate to high concentrations within intestinal cells by down-regulating NF-B activation and preventing mitochondrial dysfunction. This result was confirmed in vivo where resveratrol inhibits TNF- production and NF-B activation, decreases neutrophil infiltration in the intestinal mucosa, and represses intestinal tumorigenesis by regulating anti-inflammatory miRNA [97,98]. Chen et al. demonstrated that resveratrol significantly suppressed the TLR-4/MyD88/NF-B signaling pathway in lysophosphatidylcholine-induced damage and inflammation that might be useful for treatment of arteriosclerosis [99]. Taken together, these studies suggest that resveratrol can prevent inflammation and oxidative stress, reduce the risk of carcinogenesis and developed as anti-inflammatory agent to improve the quality of life of patients.

Resveratrol, in addition to the above described biological activities, has been studied for its ability to inhibit the growth of some pathogenic microorganisms, such as Gram-positive and Gram-negative bacteria and fungi [100]. Indeed, resveratrol has been shown to efficiently inhibit Candida albicans growth [101]. Dimethoxy resveratrol derivatives exhibited antifungal activity against C. albicans with minimum inhibitory concentration (MIC) values of 2937 g/mL, including against 11 other Candida species [102]. However, the putative candidacidal activity of resveratrol is a matter of controversy. In fact, a study indicates that resveratrol is not effective against both C. albicans and non-C. albicans species [101]. In another study, resveratrol antifungal activity against C. albicans could be reached at 400 g/mL, thereby minimizing the antifungal role of resveratrol against C. albicans-caused infections [103].

Campylobacter jejuni and Campylobacter coli are the major causes of bacterial gastroenteritis, while Arcobacter species are also known to be human and animal pathogens. Resveratrol-hydroxypropyl--cyclodextrin inclusion complexes improved resveratrol solubility and showed anti-Campylobacter and anti-Arcobacter effects. Furthermore, it inhibited biofilm formation and promoted biofilm dispersion even at sub-MIC concentrations and therefore could be developed as a new anti-biofilm agent to enhance foods shelf-life and safety [104].

Resveratrol showed antibacterial activity against Gram-positive bacteria and time-kill assays showed that its effects were due to its bacteriostatic action [105]. However, the mechanism underlying its antibacterial activity is not clearly understood [106]. Resveratrol was also able to affect cells with changes in cell morphology and DNA contents [105]. Hwang and Lim [106] demonstrated that resveratrol led to DNA fragmentation in Escherichia coli, inducing an SOS response; nevertheless, resveratrol also induced cell elongation without an SOS response and thereby inhibits bacterial cell growth by suppressing FtsZ (crucial for Z-ring formation) expression and Z-ring formation in E. coli.

From another point of view, reactive oxygen species (ROS), superoxide, peroxide, and hydroxyl radicals are thought to contribute to the rapid bactericidal activity of diverse antimicrobial agents. E. coli and Staphylococcus aureus culture supplemented with resveratrol and treated with antimicrobials reduced ROS concentrations to sublethal levels, that are mutagenic, while the absence of resveratrol allows ROS to high enough to kill mutagenized cells. Antimicrobial lethality suppression and mutant recovery promotion abilities evidenced by resveratrol suggests that this antioxidant may contribute to the emergence of several antimicrobials-resistant species, especially if new derivatives and/or resveratrol formulations markedly increase its bioavailability [107].

Pseudorabies virus is one of the devastating pathogen of swine for which there is no treatment and that often result in economic losses. Resveratrol showed antiviral activity by inhibiting the Pseudorabies virus replication and effectively increase the growth performance and reduce the mortality of Pseudorabies virus-infected piglets [108].

Pterostilbene is a methoxylated derivative of resveratrol that showed antibacterial activity against drug-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration (MIC) superior of pterostilbene compared to resveratrol (8~16-fold). Pterostilbene anti-MRSA potency was related to bacterial membrane leakage, chaperone protein downregulation, and ribosomal protein upregulation and can be topically applied for treatment of skin MRSA infection bearing it less toxicity to mammalian cells [32]. Resveratrol is a potentially useful agent on Staphylococcus aureus pneumonia and S. aureus-induced infectious diseases treatment [109]. Also, resveratrol could alleviate rotavirus infection-induced diarrhea [109].

Besides the cardioprotective, antioxidant, anticancer, neuroprotective, anti-inflammatory, anti-dyslipidemia, and antidiabetic effects of resveratrol, it also exhibits antiproliferative and androgen-lowering effects on theca-interstitial cells of ovary. Moreover, it exerts a cytostatic but not cytotoxic effect in granulosa cells, while inhibiting aromatization and vascular endothelial growth factor (VEGF) expression. These actions may be of clinical relevance in conditions associated with theca-interstitial cell hyperplasia, androgen excess, and abnormal angiogenesis, such as polycystic ovary syndrome. In addition, resveratrol may increase ovarian follicular reserve and prolong ovarian life span, serving as a potential anti-aging agent [110].

Resveratrol is also able to decrease histopathological and biochemical damages and to exert protective effects on ischemia-reperfusion injury induced ovarian damages. Resveratrol has become to continue a hotspot in many fields, including respiratory system diseases. Indeed, research has demonstrated that resveratrol is helpful in relieving pulmonary function in general population and plays a protective role in respiratory system diseases. The main protective effects of resveratrol in respiratory system diseases, including its anti-inflammatory, antiapoptotic, antioxidant, antifibrotic, antihypertensive, and anticancer activities were also examined. In resveratrol-treated patients, serum levels of certain biochemical markers (i.e., C-reactive protein, erythrocyte sedimentation rate, undercarboxylated osteocalcin, matrix metalloproteinase-3, tumor necrosis factor alpha, and interleukin-6) were also significantly decreased [111]. Therefore, the use of resveratrol as an adjuvant to conventional antirheumatic agents seems to be an optimum approach. Resveratrol can also be used as a protective and/or therapeutic agent, particularly in male infertility cases caused by testicular toxicity. On the other hand, resveratrol could be useful to protect health against several pathologies and ageing problems [84]. However, the comparative evaluation of animal and human studies shows that resveratrol cannot protect against metabolic diseases and their relevant complications. Nonetheless, it is important to point out that the clinical findings are influenced by many factors, such as sample size and study objectives. Till now, small sample size and high dosage levels were used to conduct most of clinical trials to assess resveratrol significance in chronic diseases [84]. Consequently, it is not easy to determine the exact safety range and therapeutic effectiveness of specific resveratrol doses on specific populations. In this sense, before prescribing resveratrol, patients should be properly advised for effective treatment with minimum side effects. Further evaluations are needed before declaring resveratrol as a beneficial compound for human health.

Resveratrol is widely known for its renowned beneficial biological effects, namely involving its chemopreventive and antioxidant properties. However, some studies have documented that it may behave as a pro-oxidizing agent [112]; thus, paradoxically, it may also have implication in pathology of several diseases.

Resveratrol antioxidant potential has been attributed to its ROS-scavenging capacity [112,113] and to an up regulation capacity on cells antioxidant defense [114]. Studies have reported that resveratrol could act as a signaling molecule within tissues and cells in modulating genes and proteins expression through redox-sensitive intracellular pathways activation. Thus, cell tolerance against oxidative environment could be attributed to gene expression changes and to a raise in antioxidant defense systems action and synthesis, which eventually results in cell survival and adaptation [115,116,117]. Moreover, depending on enzymatic reactions conditions, resveratrol can be (auto-)oxidized to generate semiquinones and relatively stable 4-phenoxyl radical, finally leading to ROS production [118,119]. Such polyphenols oxidative reactions are influenced by pH and presence of hydroxyl anions or organic bases [120,121].

A study carried out by Martins et al. revealed that resveratrol can modulate different pathways at a time, which can result in distinct and even opposite biological effects, depending on its concentration or treatment time defined. The authors documented that, although a dose-dependent resveratrol pro-oxidative effect leads to cells oxidative stress over lesser time exposure, at same dose but with an increase in exposure time, less expressive cytotoxicity was found. This suggest that surviving cells seemed to be more resistant to resveratrol-induced damages, being its effects attenuated over treatment time [114]. Additionally, low resveratrol doses (0.11.0 g/mL) has been documented to enhance cell proliferation, whereas higher doses (10.0100.0 g/mL) induces apoptosis () and decreases mitotic activity on human tumors and endothelial cells [122]. Recently, dual resveratrol pattern effects on HT-29 colon cancer cells death and proliferation were observed, where at low concentrations (1 and 10 mol/L), resveratrol increased cells number, while at higher doses (50 or 100 mol/L) resveratrol reduced cells number and increased apoptotic or necrotic cells percentage [123].

Diagrammatic representation of resveratrol biphasic activity and gene expression modulation. At nanomolar [124] doses, resveratrol acts as a potent antioxidant, while at micromolar (M) range, it interacts as agonist or antagonist exhibiting cell proliferation/cytoprotective responses or cytostatic/apoptotic effects, respectively.

In a very interesting study, dose-time dependency of acute resveratrol administration on lipoperoxidation levels (in heart, liver and kidney of male rats synchronized with a 12-h dark-light cycle) was investigated. It was documented that resveratrol behaved as an antioxidant during dark span and as a pro-oxidant during light span, possibly reflecting the putative changing ratio between pro- and antioxidant activities in various organs during 24-h cycle or postprandial oxidative burst that occurred after a meal [124]. There is an interesting correlation among dietary polyphenols pro-oxidant and cytotoxic activities, such as to resveratrol. In fact, since every antioxidant is a redox agent it might become a pro-oxidant, accelerating lipid peroxidation and/or inducing DNA damages under special conditions. In this way, it has been proposed that such pro-oxidant action could be an important mechanism of action to resveratrol anti-cancer and apoptotic-inducing properties [112]. It has already been reported that resveratrol can lead to DNA damages, as well as to a reversible or irreversible cell cycle interruption mediated by its pro-oxidant effect [117]. Recently, Plauth et al. [125] proposed that cellular response to resveratrol treatment is based on oxidative triggering action, that can lead to cell fitness hormetic induction towards a more reductive state, so as to physiological resilience raising in fight oxidative stress. Also, it has been reported earlier that a critical balance between intracellular hydrogen peroxide (H2O2) and O2 decides cells fate to apoptotic stimuli. Thus, a shift towards H2O2 favors apoptosis, whereas inclination towards O2- obstructs apoptosis. Indeed, H2O2 promotes apoptosis by reducing intracellular O2- concentration and triggering cytosolic pH drop. Ahmad et al. [126] reported that resveratrol inhibitory effect on H2O2-induced apoptosis is not due to its antioxidant activity, but rather, through a pro-oxidant effect evidenced by the prominent raise in intracellular O2- production, which creates a non-conducive intracellular environment for apoptotic execution.

Regarding antioxidant/pro-oxidant hydroxystilbenes (resveratrol) activities, various studies were performed in the past aiming to define its structureactivity relationship, using cell-free systems [127,128]. Thus, Rweler et al. [117] found that neither cytotoxic or cytostatic activities nor cytoprotective and antioxidant activities in cultured (C6 glioma) cells are indicative of a structureactivity relationship stressing the need to explore mechanisms at molecular level. Fukuhara and Miyata, firstly reported resveratrol pro-oxidant activity in a plasmid-based DNA cleavage assay, in the presence of transition metal ions, such as copper, the most redox-active metal ions present in nucleus, serum and tissues [129,130]. Resveratrol is closely linked with DNA bases, particularly guanine [131]. Copper ions from chromatin can be mobilized by metal-chelating agents, giving inter-nucleosomal DNA fragmentation rise, a property that is considered the hallmark of cells undergoing apoptosis. Recently, resveratrol mutagenicity in plasmid DNA was reported via point mutations (deletions/substitutions), resulting in many guanine bases deletion. In fact, since copper ions are known to be found in a nucleus bound to guanine bases in chromatin, the mobilization of such endogenous copper by resveratrol result in pro-oxidant DNA cleavage at the site. Moreover, copper concentration is reported to be raised in various malignancies; so, this study explains resveratrol anticancer activity [132].

Based on its structural similarity to diethylstilbestrol, a synthetic estrogen, resveratrol can also acts as a phytoestrogen, exhibiting variable estrogen receptor agonist degrees in different systems [133]. In some cell types, resveratrol acted as a super agonist, whereas in other ones, it produced an equal to or lesser activation than that of estradiol, and as an antagonist at higher concentrations. Such concentration-dependent agonist and antagonist behavior was employed to account for mechanisms underlying biphasic concentration response. At concentrations similar to those required for its other biological effects, resveratrol inhibited labelled estradiol binding to estrogen receptor and activated estrogen-responsive reporter genes transcription transfected into human breast cancer cells [133]. Besides, in absence of estrogen (E2), resveratrol exerts mixed estrogen agonist/antagonist activities in some mammary cancer cell lines, but in the presence of E2, resveratrol acts as an anti-estrogen [134]. In another report, it was demonstrated that resveratrol abolishes serum deprivation-induced elevated caspase 3 activity, suggesting its rescue effect via p38 MAPK signaling [135]. Resveratrol also regulates mitochondrial respiratory chain function, with mitochondrial complex I (CI) as a direct target of this molecule. It was also in vivo demonstrated that, in young and old mice brain mitochondria, resveratrol increased CI, while in aged animals with low antioxidant defenses led to oxidative stress. Therefore, not only dose, but also age at the time of treatment, can modulate intracellular and mitochondrial redox status, switching from resveratrol beneficial to deleterious effects, highlighting the importance of a balance between resveratrol pro- and antioxidant effects, that depends on its dose and age as well [136]. Yang et al. [137] reported dual resveratrol roles in pancreatic cancer cells: one as a tumor suppressor through Bax up-regulation, and the other one as a tumor activator through VEGF-B up-regulation; so, resveratrol anticancer effect is much stronger than cancer promotion effect.

All the above highlighted studies show the pivotal role of dose-dependency and aging in resveratrol-induced responses towards health benefits. Also, in another study, aiming to compare resveratrol effects on aging-induced and re-nutrition-induced insulin resistance and its consequences on arterial system, the authors found that resveratrol improved insulin sensitivity in old mice fed standard diet, while did not improve insulin resistance status in old mice receiving high-protein diets. In contrast, resveratrol exhibited deleterious effects by increasing inflammation state and superoxide production and decreasing aortic distensibility. This data demonstrates that resveratrol seemed to be beneficial to malnourished state of physiological aging, whereas when associated with high protein diets in old mice, may increase atherogenesis-associated risk factors by triggering vascular alterations that could represent an additional risk factor for cardiovascular system [138].

One of the most fascinating resveratrol aspects for its future development as a promising drug is that, it does not appear to have debilitating or toxic side effects. A wide range of resveratrol doses has been used in various in vivo and in vitro studies. However, it is imperative to find out the most appropriate dose and administration route. Also, it was documented that resveratrol induces cell death in tumor tissues with relatively no effect in normal adjacent tissues [52]. Resveratrol cell uptake disparity between normal and tumor cells may be attributed to differences in available cellular targets and gene expression in cancer cells, which makes resveratrol tumor-specific. Mukherjee et al. [139] have suggested that lower resveratrol doses could be associated with health benefits, while higher doses devastate tumor cells via pro-apoptotic effects.

Resveratrol does not appear to have side effects at short-term doses (1.0 g). Otherwise, at doses of 2.5 g or more per day, side effects may occurs, like nausea, vomiting, diarrhea and liver dysfunction in patients with non-alcoholic fatty liver disease [140]. Interestingly, no major side effects were stated in long-term clinical trials [141]. In fact, resveratrol has been found to be safe and well-tolerated at up to 5 g/day, either as a single dose or as fraction of multiple-day dosing schedule [142]. However, it is imperative to mention that these studies were done in healthy populations, and that may vary in sick patients. Our understanding of resveratrol dose-dependency and administration route is further complicated, since orally administrated resveratrol gets metabolized by gut microbiota [143], which makes it difficult to determine which effects are solely due to resveratrol or both resveratrol and its metabolites.

To investigate the assumption, whether resveratrol inhibit atherosclerotic development in hypercholesterolemic rabbits, Wilson et al. [144] supplemented rabbits with or without oral resveratrol (1mg/kg), and found that resveratrol treatment did not adversely affect rabbits health other than promoting atherosclerosis. Plasma LDL electrophoretic mobility was not different between groups. Atherosclerotic lesions staining in control and resveratrol-treated groups revealed that resveratrol-treated rabbits had significantly more aortic surface area covered by atherosclerotic lesions. Therefore, resveratrol promoted atherosclerotic development, rather than protect against it, by an independent mechanism of differences observed in gross animal health, liver function, plasma cholesterol concentrations, or LDL oxidative status [144]. Ferry-Dumazet et al. [145] aiming to analyze resveratrol nephrotoxicity effects, given orally 3000 mg/kg b.w. to rats for 28 days. It resulted in nephrotoxicity documented as elevated serum blood urea nitrogen and creatinine levels, increased kidney weights, gross renal pathology changes, and an increased incidence and severity of histopathological changes in kidneys. Kidneys microscopic evaluation identified lesions whose pathogenesis could be increased by resveratrol concentration (or its metabolite) as a function of renal osmotic concentration gradients, resulting in toxic levels in renal pelvis. This would result in necrosis, renal tubules obstruction and thus tubules dilation behind obstructed region. Indeed, inflammation and pelvic epithelium hyperplasia are expected responses to the presence of necrotic tissues. Therefore, administration of 1000 or 300 mg resveratrol/kg b.w./day did not result in nephrotoxic findings. The predominant clinical signs of toxicity at 3000 mg/kg b.w./day dose group were dehydration, piloerection, and red material in cage/urine, body weight gain reduction, hyperalbuminemia, anemia (due to renal injury, which reduced erythropoietin synthesis), white blood cell counts increase due to renal pelvic inflammation. Moreover, increased ALT, ALKP and total bilirubin levels suggest liver toxicity, but this was not histologically supported. Similarly, organs evidencing weight change did not evidenced histological changes [146].

Resveratrol has been reported to both reduce cell growth and induce apoptosis in normal cells, when administered at high doses, which confirm its biphasic effects over low to high concentrations spectrum [145]. Resveratrol rapidly activate mitogen-activated protein kinase (MAPK) in a MEK-1, Src, matrix metalloproteinase, and epidermal growth factor receptor in a dependent manner. It activates MAPK and endothelial nitric-oxide synthase (eNOS) at nanomolar concentrations (i.e., magnitude less than that required for ER genomic activity) and at concentrations possibly/transiently achieved in serum following oral red wine consumption [147]. Additionally, resveratrol consumption at modest doses result in a life span increase in 1-year old mice. However, when mice consumed larger resveratrol doses (1800 mg/kg), animals were shown to die within 34 months [148]. Studies on steady-state pharmacokinetics and tolerability of 2000 mg trans-resveratrol, administered twice daily with food, quercetin and alcohol (ethanol) showed that trans-resveratrol was well-tolerated by healthy subjects, although diarrhea was frequently observed [149].

The use of natural products is prevalent among patients who are taking conventional medicines, leading to a higher risk of natural product-drug interactions. Resveratrol may interact with several medications. It may lead to interactions with various cytochrome P450 (CYP), especially when taken at high doses [150]. Resveratrol has been reported to inhibit CYP3A4 activity, in vitro [151] and in healthy volunteers [152]. Therefore, high resveratrol intakes even in through form of supplements with additional medications could potentially reduce drugs metabolic clearance that undergo extensive first-pass CYP3A4 metabolism, hence increasing both bioavailability and toxicity risk of these drugs. Since this polyphenol has been reported to have significant interactions with phase I and II enzymes both in vitro and in vivo [153], they may be beneficial or harmful as well. Indeed, individuals taking drugs, such as tamoxifen, whose efficacy is highly specific and CYP enzymes-dependent, could be particularly affected. Therefore, caution should be taken when using supplemental resveratrol doses for health benefits, such as chemoprevention.

Aside from drug metabolizing enzymes, it is now greatly acknowledged that transport function modifications are involved in these resveratrol-drug interactions. Resveratrol has been reported to potently inhibit P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2), and organic anion transporter 1/3 (OAT1/OAT3) [154]. Nonetheless, resveratrol interactions with transporters are still not fully elucidated. Furthermore, few clinical studies were conducted to determine transporter-mediated resveratrol-drug interaction. On the other hand, it is also speculated that higher resveratrol doses compete with other polyphenols for transporters, reducing both their uptake and potential synergistic effects. Moreover, absorption, distribution, renal excretion, and/or hepatic elimination of resveratrol active ingredients in humans is not well-explored than required for actual resveratrol-drug interactions prediction. Thus, resveratrol modulating effects on transporter-drug interactions warrants further investigation.

Resveratrol has been reported to hinder human platelet aggregation in vitro [155,156]. Presumably, high resveratrol intakes in the form of supplements could enhance both bruising and bleeding risk when taken with anticoagulant drugs, antiplatelet drugs and even non-steroidal anti-inflammatory drugs (NSAIDs).

Resveratrol is a nutraceutical belonging to stilbenoid group, widely distributed in the plant kingdom and with several therapeutic effects. Structurally, stilbenoids possess two aromatic rings linked by an ethylene or ethene bridge with a variety of substituents. Even though, the presence of double bond suggests that stilbenoids exist in cis- as well as trans-form. trans-form is more stable and with high bioactive effects. Resveratrol molecules are synthesized from phenylalanine pathway through multiple enzymatic reactions. Traditionally, resveratrol has been used for stomachache, hepatitis, arthritis, urinary tract infections, fungal diseases or skin inflammation treatment, but the main biological potential of resveratrol belongs to cardioprotection.

Apart from its cardioprotective effects, resveratrol also exerts anticarcinogenic, antiviral, neuroprotective, anti-inflammatory and antioxidant properties. Resveratrol-like other derivatives are one of the most promising compounds on anti-inflammatory drug formulation. Nevertheless, its attractiveness, amendments to their structure/bioavailability/activity must be increased. Also, it has been shown that is able to mimic caloric restriction effects, exert anti-inflammatory and antioxidant effects, and even affect many diseases initiation and progression through several mechanisms. While there is a wealth of in vitro and in vivo evidence that resveratrol could be a promising therapeutic agent, clinical trials must confirm its potential.

N. Martins would like to thank the Portuguese Foundation for Science and Technology (FCTPortugal) for the Strategic project ref. UID/BIM/04293/2013 and NORTE2020Programa Operacional Regional do Norte (NORTE-01-0145-FEDER-000012).

All authors contributed equally to this work. B.S., M.S.-R., P.V.T.F., N.M., and J.S.-R., critically reviewed the manuscript. All the authors read and approved the final manuscript.

The APC was funded by N Martins.

The authors declare no conflict of interest.

Read more:
Resveratrol: A Double-Edged Sword in Health Benefits - PMC

Resveratrol is a polyphenolic nutraceutical that exhibits pleiotropic activities in human subjects. The efficacy, safety, and pharmacokinetics of resveratrol have been documented in over 244 clinical trials, with an additional 27 clinical trials currently ongoing. Resveretrol is reported to potentially improve the therapeutic outcome in patients suffering from diabetes mellitus, obesity, colorectal cancer, breast cancer, multiple myeloma, metabolic syndrome, hypertension, Alzheimer's disease, stroke, cardiovascular diseases, kidney diseases, inflammatory diseases, and rhinopharyngitis. The polyphenol is reported to be safe at doses up to 5 g/d, when used either alone or as a combination therapy. The molecular basis for the pleiotropic activities of resveratrol are based on its ability to modulate multiple cell signaling molecules such as cytokines, caspases, matrix metalloproteinases, Wnt, nuclear factor-B, Notch, 5'-AMP-activated protein kinase, intercellular adhesion molecule, vascular cell adhesion molecule, sirtuin type 1, peroxisome proliferator-activated receptor- coactivator 1, insulin-like growth factor 1, insulin-like growth factor-binding protein 3, Ras association domain family 1, pAkt, vascular endothelial growth factor, cyclooxygenase 2, nuclear factor erythroid 2 like 2, and Kelch-like ECH-associated protein 1. Although the clinical utility of resveratrol is well documented, the rapid metabolism and poor bioavailability have limited its therapeutic use. In this regard, the recently produced micronized resveratrol formulation called SRT501, shows promise. This review discusses the currently available clinical data on resveratrol in the prevention, management, and treatment of various diseases and disorders. Based on the current evidence, the potential utility of this molecule in the clinic is discussed.

Keywords: chronic diseases; clinical trial; nutraceutical; pharmacokinetics; resveratrol.

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Health benefits of resveratrol: Evidence from clinical studies

How do the French eat more fat, sugar and rich foods, plus drink more wine, but still have less heart health issues? The answer to this puzzling question, commonly known as the french paradox, is believed to be due to a higher intake of a specific phytonutrient called resveratrol, found naturally in superfoods like red wine. Like other antioxidants and phytonutrients, such as lycopene found in tomatoes or lutein found in carrots, resveratrol is a powerful compound that regenerates the body all the way at the cellular level.

Research published over the past several decades in many medical journals, including the European Journal of Food Pharmacology andAmerican Journal of Hypertension,found that resveratrol (in this case from red wine) decreases the risk of heart disease among other common health concerns.

Although he might not have known exactly how wine was able to promote better health, even Plato promoted the health perks of drinking it in moderation. Hes been quoted as saying, Nothing more excellent or valuable than wine was ever granted by the gods to man. (1)

In case youre wondering, you dont have to be a wine drinker to benefit from resveratrol. Other sources include deeply colored berries and real dark chocolate and cocoa. Along with helping to keep arteries clear from plaque buildup and protecting an aging heart, this phytonutrienthas many other health benefits too including reducing inflammation, potentially helping to prevent obesity and protecting cognitive health among the elderly.

Resveratrol is a polyphenic bioflavonoid antioxidant thats produced by certain plants and found in foods and drinks that are known to halt the effects of aging. Resveratrol is classified as aphytoestrogen because of its ability to interact with estrogen receptors in a positive way.

Plants that produce resveratrol and other types of antioxidants actually do so partly as a protective mechanism and response to stressors within their environments, including radiation, the presence of insects or other predators, injury, and fungal infections. Today, resveratrol is believed to be one of the most potent polyphenols and strongest protectors against symptoms associated with aging andfree radical damage.

Studies show that the most naturally abundant sources of resveratrol (not to mention many other protective phytonutrients, vitamins and minerals) are plants, including the skin of red grapes, red wine, raw cocoa, and dark berries, such as lingonberries, blueberries, mulberries and bilberries.

Red wine is probably the best known source, mostly due to its high levels thanks to the fermentation process that turns grape juice to alcohol. During production of red wine, grape seeds and skins ferment in the grapes juices, which have positive effects on levels and availability of resveratrol.

The benefits of resveratrol were first discovered when researchers found that yeast and other microbes, insects and animals fed resveratrol experienced an increased life span as a result. Various studies continued to confirm its amazing anti-aging benefits, demonstrated in studies conducted on fruit flies, fish, mice and nematode worms, all of which lived longer compared to control groups that were not treated with this phytonutrient.

Related: Fisetin: A Senolytic Antioxidant for Healthy Aging & More

Resveratrol is a powerful antioxidant that neutralizes free radicals produced during everyday bodily functions, such as eating and exercise. Free radical damage is accelerated due to poor lifestyle habits like smoking, eating an unhealthy diet, and in response to environmental pollution and toxicity.

If left unchecked, free radicals can damage cells and are thought to be a cause of life-threatening diseases andearlier death. Consuming plant foods high in antioxidants and phytonutrients has been shown to offer antioxidative, anticarcinogenic and antitumor benefits that protect adults from many age-related diseases. (2)

According to research published by the Department of Pharmacology at the University of Seville in Spain, One of the most striking biological activities of resveratrol soundly investigated during the late years has been its cancer-chemopreventive potential. In fact, recently it has been demonstrated that it blocks the multistep process of carcinogenesis at various stages: tumor initiation, promotion, and progression.

Its believed the mechanisms for its cancer-protecting activities involves downregulation of the inflammatory response through inhibition of synthesis and release of pro-inflammatory mediators, among other activities. (3)

Because of its anti-inflammatory activity, resveratrol has been shown to offer protection against atherosclerosis (thickening of the arteries that cuts off blood flow), high LDL bad cholesterol, formation of blood clots and myocardial infraction. Consuming more has also been shown to help improve circulation and have beneficial effects on glucose and lipid metabolism in some with higher risk for metabolic syndrome. (4)

Itadori tea, one significant source of resveratrol, has long been used in Asian countries, including Japan and China, as a traditional herbal remedy for preventing heart disease and strokes.

Resveratrol is particularly unique as its antioxidants can cross the blood-brain barrier to protect the brain and the nervous system, unlike other antioxidants. Recent studies done by researchers at the Nutrition Research Center at Northunbria University in the U.K. showed that resveratrol noticeably increased blood flow to the brain, suggesting a considerable benefit to healthy brain function and neuroprotective effects.

This means consuming more can increase protection against cognitive/mental problems, including Alzheimers, dementia and others. Other study findings, such as results published in the Journal of Agricultural Food Chemistry, demonstrated that even a single infusion of resveratrol could elicit neuroprotective effects on cerebral (brain) neuronal loss and damage. (5) This resulted from increased free radical scavenging and cerebral blood elevation due to resveratrols effects.

Findings from animal studies have found that resveratrol exerts beneficial effects on rodents fed a high-calorie diet, helping prevent fat storage and regulating insulin levels. (6) Others research has shown that resveratrol may help reduce body weight and adiposity in obese animals, which some experts believe is due to activating the SIRT1 gene thats believed to protect the body against the effects of obesity.

Its not totally clear how this translates to humans consuming foods or drinks like wine and berries, but studies have found links between adults eating balanced diets that include moderate amounts of wine and healthier body weights.

Animal studies involving diabetic rats have demonstrated that resveratrol may be able to reduce hyperglycemia and may also possibility be of use in preventing and/or treating both obesity and diabetes.

Resveratrol may be helpful for those with diabetes and prediabetes byreducing complications (like nerve damage and damage to the heart) and helping manage insulin levels. Its known that this phytoestrogenpositively affects insulin secretion and blood insulin concentrations, according to animal studies. (7)

As you can tell from all the benefits described above, resveratrol and sources that provide it, including red wine, are more than just powerful heart-protectors. Theyre also strong brain-boosters, among many other things. People use resveratrol for all sorts of anti-aging benefits, considering research suggests that itcan help:

Should You Take Resveratrol Supplements?

Because the FDA does not regulate supplements, many health authorities are not convinced that taking resveratrol supplements or extract will have much payoff. As with all herbs and extracts, you cant be sure exactly what youre getting and how effective the product may be.

Dosage recommendations vary depending on your current health and symptoms, but most resveratrol supplements are typically taken in about 250 to 500 milligrams/day dosages. Its important to point out that this is generally lower than the amounts that have been shown to be beneficial in studies, but its not clear if taking very high doses is safe.

Some adults choose to consume up to two grams daily (2,000 milligrams). (8) According to the New York Academy of Sciences, studies have found resveratrol to be safe and reasonably well-tolerated at doses of up to five grams per day, but this shouldnt be taken without speaking with your doctor. (9)

Its possible, however, to experience mild to moderate side effects at higher doses, so experts recommend starting with less until further studies demonstrate any added benefit of taking more. Resveratrol supplements may potentially interact with blood thinners like warfarin (Coumadin) and NSAID pain relievers (like aspirin or Advil), so be sure not to mix these.

Resveratrol works by modifying inflammation in the body, in addition to having other positive effects on hormone production, blood circulation and fat storage. Studies demonstrate that itspecifically seems to work in some of the following ways:(10)

Now you know the benefits of resveratrol in your diet, you may be wondering what the best source of this compound is. Below are the best foods and beverages to add to your diet (albeit in moderation) in order to consume more resveratrol:

Different plants supply various forms of resveratrol. For example grapes, peanuts and Itadori tea contain mainly trans-resveratrol glucosides. Red wine is primarily a source of the aglycones cis- and trans-resveratrol.

Studies show that both Itadori tea and red wine supply relatively high concentrations of resveratrol compared to most other foods. Itadori tea is a good option for people who avoid drinking alcohol or for children.

Although we have mentioned that red wine and cocoa are two of the best sources of resveratrol, unfortunately a diet of dark chocolate and red wine may be decadent but ultimately very unhealthy if you overdo it. The best way to obtain the benefits of resveratrol is through balance and moderation.

We recommend consuming wine in small amounts, about one glass per day or less; according to most research, up to two glasses daily for men and one per day for women hasnt been shown to cause any health concerns. If you do choose to take resveratrol supplements, still aim to consume antioxidants naturally from a healthy diet, including a variety of fresh plant foods.

While a large body of evidence has already suggested that resveratrol has many benefits, many experts feel that before we can promote drinking more wine or taking supplements to all adults, additional research is still needed. Overall, theres support for its positive attributes, but data is still needed to confirm its effectiveness for prevention of actual diseases in humans.

Its still not completely known how different people react to resveratrol and if some benefit more than others. For example, people with existing cases of diabetes or metabolic defects may need to take higher doses than mostly healthy adults to get the same effects. Talk to your doctor if you plan on taking supplements and are already on other medications.

Overall, most of the benefits of resveratrol have been shown in animal studies and at high dosages. Harvard School of Public Health points out, The dose of resveratrol administered in experiments is always much higher than youd normally consume in a daily diet. You would need to drink a hundred to a thousand glasses of red wine to equal the doses that improve health in mice. (11)

That being said, resveratrol is not a cure-all and means to living a longer, disease-free life. It may be one piece of the puzzle, but the bottom line is that it probably shouldnt motivate you to drink more wine than you already are.

More here:
Resveratrol Benefits, Side Effects and Food Sources - Dr. Axe

Every person around the globe is aware of peanuts - crunchy and tiny nuts. These nuts or legumes make a mouth-watering side meal and come in handy whenever you are craving a delicious snack, especially during fasting and weight loss routine.

Peanuts are super rich in several minerals, micro and macro-nutrients, and vitamins, are highly affordable, and are a versatile ingredient - when compared to any other variety of nuts. Either raw or roasted, whatever form you choose to consume these tasty nuts, one thing is for sure - that you will end up with loads of health benefits, including strong heart health, beautiful skin, shiny hair, energy boost, and a good night's sleep.

Hence, this article. Today, we will talk about everything related to peanuts - from its definition, types, and nutritional facts to health benefits and also potential risks (if consumed in a heavy dose regularly).

Grab a handful of peanuts while you give this article a read. Let's start!

Peanuts are a type of legume that are surprisingly related to lentils, beans, and soy, and not to tree nuts.

Peanuts (Arachis hypogaea) originated in South America and are known by a variety of names, like earthnuts, groundnuts, and goobers.

The most popular type of peanut consumption is either raw (along with a pinch of tangy, salty powder) or in the form of peanut butter (both smooth and crunchy).

Yes, you read that right. Peanuts have a variety, as per the National Peanuts Board. There are four types of Peanuts -

With big kernels and premium characteristics, this type of peanut is known as a gourmet peanut. Due to their large size and pretty form, Virginia peanuts are best suited for snacking. This variety of peanuts is grown in Virginia, Carolinas, Texas, Florida, Oklahoma, Georgia, and New Mexico regions.

Runner peanuts are widely used to prepare peanut butter and other such confections. This type of peanut makes up 80% of the peanuts grown in the U.S.

With a slightly sweet flavor profile, Valencia peanuts make for all-natural peanut butter and an excellent boiled snack. This type of peanut makes up lesser than 1% of the peanuts grown in the U.S. and is mainly grown in the New Mexico and Texas regions.

The type of Peanuts with red skins and a nutty flavor profile is called Spanish peanuts. They are mainly consumed after roasting and have a slightly higher oil content, which adds depth to their overall nutty flavor. They are usually grown in New Mexico, Oklahoma, and Texas regions and are widely used in confections, candy, and peanut butter.

Peanuts are loaded with high-quality protein and healthy fats. Here is the nutrition profile for 3.5 ounces (100 grams) of raw Peanuts -

1. Calories (or Energy) = 567 kcal

2. Water content = 7%

3. Fat = 49.20 gm

4. Omega-3 = 0 gm

5. Omega-6 = 15.560 gm

6. Macronutrients:

7. Minerals:

8. Vitamins:

9. Fat:

Apart from these, Peanuts also contain a rich amount of biotin and copper - all of which are essential to reduce the risk of multiple ailments and maintain body metabolism.

Peanuts are versatile, flavorsome, and jam-packed with crucial nutrients, offering numerous health benefits, including supporting heart health, promoting muscle growth, losing weight, enhancing sexual function, etc. A plethora of health benefits of Peanuts as discussed below -

Consuming Peanuts every day in moderation helps those who are aiming to shed some extra kilos. Although Peanuts have a high-calorie level, they are all good fats. Add this to the high protein content, and Peanuts become great for weight loss by providing high satiety value. Not to forget that eating more protein reduces the level of Ghrelin, a-k-a, the hunger hormone, in your body. Thus, increasing the production of Peptide YY (a hormone which is responsible to make you feel full). Therefore, preventing you from binge eating.

Multiple studies have proven that consuming Peanuts tends to decrease the chances of heart diseases. Peanuts consist of nutrients that are crucial for having a healthy heart. These nuts contain copper, magnesium, protein, antioxidants (like Resveratrol), a healthy ratio of unsaturated and mono-unsaturated fats, and fiber that altogether help in reducing your bad cholesterol levels. Peanuts also contain antioxidants and amino acids that keep the inner lining of your arteries safe, thereby protecting your heart against heart problems like atherosclerosis. Also, as per a research published in the New England Journal of Medicine, a daily dose of these crunchy nuts reduces the risk of death from heart disease by 29%.

Peanuts consist of antioxidants (like Resveratrol) and mono-unsaturated fats that make your skin clear. These nutrients also wash away all the toxins from your body that make your skin appear dull, greasy, and lifeless. The antioxidant, Resveratrol, even delays the signs of aging, including fine lines, wrinkles, and dark spots. Additionally, this antioxidant is a scientifically proven cure for skin diseases like Eczema and Psoriasis.

Research shows that Vitamin E and Vitamin C present in the Peanuts protect your skin against the harsh UV rays of the Sun from causing any subsequent damage. Plus, the presence of Vitamin C also gives elasticity to your skin, making it look brighter, younger, and smoother.

To keep your brain healthy, active, and sharp, you obviously require rich nutrients like Vitamin B1, Folate, and Niacin. When you include Peanuts in your daily meal, your body tends to fuel up with these nutrients. And as a result, your brain becomes more active, healthy, and sharp. Vitamin B1 and Niacin also help to protect your brain against diseases like Alzheimers and age-related cognitive decline. Moreover, Peanuts are jam-packed with a bioactive antioxidant called Resveratrol, which improves verbal fluency and cognitive abilities in people. Also, Polyphenols present in Peanuts are called mood food that helps against cognitive and psychiatric disorders, which, in turn, keeps your brain healthy.

The requirement of protein necessary for the proper and healthy growth of children can be fulfilled by eating Peanuts on a daily basis. Peanuts are loaded with protein, making about 22% to 30% of their total calories. This protein helps in building muscle mass while promoting muscle growth and supporting bone health. Plus, adequate protein intake also helps to speed up any wound healing. Additionally, adding Peanut butter spread on toast or crackers makes a great and super tasty pre-workout or mid-day snack while adding to your total protein intake.

Aging in people causes the weakening of many bones present in your body. Therefore, before your bones start losing their agility and strength, you must focus on eating healthy and nutrient-rich food options like Peanuts. Plus, Peanuts are rich in phosphorus and manganese. These nutrients and other essential Vitamins that are present in Peanuts help to keep up and maintain the strength of your bones, thereby assisting you in your old age.

When it comes to the maintenance of your eye health, a few green leafy vegetables and Peanuts are considered the best food items that you should consume. The presence of Zinc in Peanuts helps your body to transfer Vitamin A, which is highly crucial for clear and healthy eyesight and vision. Also, the presence of Vitamin E in Peanuts helps to slow down cataract formation and any other age-related macular degeneration or illness.

Peanuts are super rich in an essential amino acid, Arginine, that has been studied extensively and thoroughly as a possible treatment and cure for erectile dysfunction. However, there is still more research required to understand if Arginine alone can help to treat erectile dysfunction. But, research analyses confirm that oral administration of this amino acid when combined with a herbal supplement, Pycnogenol, may help in the treatment of erectile dysfunction.

Peanuts are a great source of healthy fats that mostly come from Oleic acids, which are also found in olive oil. This particular acid present in the Peanuts truly helps to fight against inflammation and other free radicals in your body cells.

Since Peanuts have no sugar content, they are completely safe for all diabetic patients. Plus, these nuts are a rich source of vital nutrients and are truly delicious at the same time. Also, research shows that eating Peanuts (especially in the morning) can help you to keep a check on your blood sugar level throughout the day. And it may also prevent insulin spikes to some extent if and when you eat sugary foods. As per a research study by The American Medical Association, regular (and controlled) consumption of Peanuts actually strengthens your bodys natural ability to regulate and maintain its insulin levels against Type 2 diabetes.

Thorough researches have shown that consuming Peanuts can reduce the risk of cancer. Plus, Peanuts have an excellent amount of Vitamin E and protein that helps to lower the risk of cancer. Also, these legumes have a good content of antioxidants like Resveratrol, which further helps in preventing cancer by cutting off the blood supply to your growing cancer and restraining cancer cell growth.

Around 25% of adults suffer from gallstones - a disease caused by uncontrolled levels of bad cholesterol - every year. Since Peanuts control cholesterol levels, eating an adequate amount of Peanuts may reduce the risk of gallstones in adults as well as in children.

Peanuts are jam-packed with an amino acid, Arginine, that is converted into Nitric Oxide - a compound that helps to dilate your blood vessels to improve overall blood flow and circulation. Studies show that taking Arginine supplements may help in the treatment of mild to moderate erectile dysfunction, enhancing sexual function. Other test-tube studies have found that Arginine can also enhance libido, improve semen quality, and increase your overall testosterone levels. Additionally, Peanuts are a very good source of antioxidants like Resveratrol that have proven to support and enhance sexual health in men by improving erectile function and sperm quality. However, more research is still needed to determine if Peanuts specifically can affect sexual function.

Contrary to a popular belief (rather a myth), adding Peanuts or Peanut butter to your meal does not spike your blood sugar levels. Rather, having them alongside your meal high in GL (like a glass of juice or a savory bagel) may actually stabilize your blood sugar levels. That is probably the reason why the American Diabetes Association names Peanuts among the diabetes-friendly superfoods. Furthermore, the fiber content found in Peanuts also helps to lower your blood sugar levels. And these nuts also contain magnesium and several other healthy oils that play a vital role in managing, controlling, and balancing your blood sugar levels.

Eating Peanuts daily in an adequate amount is healthy and good, but overeating them obviously may backfire just like with any other food. However, aside from Peanut allergies, eating them has not been linked to many severe adverse effects. Still, below are some possible side effects of Peanuts that you should consider and know.

Read more:
Peanuts: Best guide to learn health benefits, nutrition and side effects - PINKVILLA

Moderate wine consumption is believed to have several advantages. Health benefits of red wine aside, unwinding with a cold glass of the beverage after a hectic day is like a much-needed hug for the soul. Right from Biblical times, wine has been presented as a sacred elixir which is healing, soothing and even life-giving. This, probably, makes it one of the most loved alcoholic beverages worldwide. The benefits of red wine are thus something you should know about.

A glass of red wine is like a best friend we cant do without owing to its versatility. A reliable party companion, a key ingredient in your signature recipe, a therapist and a confidante drinking red wine can mean different things to different people.

However, knowing the right bottle of red is a form of art, which sommeliers spend decades mastering by unravelling the mystery behind this deep, richly textured magic potion. But in addition to its major cultural relevance, its also touted to have health benefits, while avoiding excessive drinking.

Making, ageing and preserving wine is an art which has been perfected for over 8,000 years. While there have been changes in the types of equipment used with innovative technology, the basic method remains true to its origin. Specially cultivated grapes go through around 12 steps before reaching your table in a rich, red, consumable form.

A special variety of black (or purple) grapes rich in anthocyanin gives red wine its signature red colour. They are harvested when perfectly ripe and prepared for fermentation. Harvesting grapes for wine is the primary step in winemaking as well as for cultivators who own some of the best vineyards.

Then, the grapes are taken to the winery where yeast is added to the fermentation process a crucial stage of red winemaking. This process is critical for the wines colour, texture and aroma. Different methods are employed to extract the flavours from grape skins and other fermenting elements.

The grapes are then transferred to a press. Making red wine is a little more complicated because the pressed grape liquid goes through fermentation once again while they are stored in barrels and containers of different types. The quality of red wine depends on how well it has been aged and rested.

Winemakers do a final blending of two or more grape liquids, which gives the wine a more nuanced taste. Each red wine type be it Shiraz, Merlot, Cabernet Sauvignon, Zinfandel or Pinot Noir gets its unique texture and flavour from such processes. The liquid is then filtered and bottled. At this stage, bottled wine is aged again in a cellar before it is ready to be consumed.

It is believed by some that moderate drinking of red wine should no longer be a guilty pleasure, as it has several health benefits.

Resveratrol, an antioxidant found in the skins of black grapes used to make red wine, might be linked to reducing heart diseases. It is touted that drinking red wine can reduce bad cholesterol and the subsequent formation of blood clots in the body.

A Science Direct report (2005) claims that this antioxidant does not directly reduce the risk of cardiovascular diseases but the resveratrol present in it may prevent damage to blood vessels along with another compound procyanidins found in the grapes. Reports studying the implication of red wine on cardiovascular health suggest that people who generally consume antioxidant-rich whole foods with a light to moderate quantity of red wine have decent heart health.

An NCBI report (2021) states that by drinking red wine in moderation, useful compounds are secreted in blood flow which in turn make positive changes in our bodys metabolic profile with an increase in fatty acids, cholesterol, branched-chain amino acids, ketone bodies, bacterial co-metabolites and cellular antioxidants. The report adds that drinking red wine might increase your longevity by seven percent.

Another red wine health benefit is associated with the improvement of gut bacteria in the body. A 2015 Medical News Today study states that resveratrol found in red wine is a natural phytoalexin, which encourages the formation of good gut bacteria which act like probiotics. The research is still ongoing to unlock the maximum health benefits of red wine on the gut.

This one is a bit of a paradox because excessive alcohol consumption is linked to an increase in depression. Still, studies show that moderate red wine consumption on a daily basis can help in beat stress and put you in a relaxed mood.

Resveratrol seems to be the magic ingredient found in red wine, as it is also linked to preventing cancer. Drinking red wine in moderation can unlock protective elements present in resveratrol, which work against the growth of cancer cells in the body. Though regular alcohol consumption raises breast cancer risk, red wine is an exception to this. Red wine has the opposite effect when consumed in moderation as reported by researchers from Cedars-Sinai Medical Center in Los Angeles in the Journal of Womens Health.

A BMJ medical report published in 2018 states that individuals who have never consumed alcohol, especially red wine, are at an increased risk of disorders including dementia and Alzheimers. One of the major health benefits of polyphenols, found in red wine, is that it has neuroprotective qualities. Thus, moderate red wine consumption might actually be helpful.

While sipping wine has been associated with wellness, in addition to relieving emotional stress, the key, as confirmed by research, is moderate red wine consumption. To get the most health benefits from this evergreen drink, doctors suggest that both men and women should limit their red wine consumption to two glasses per day. Additionally, individuals with a medical condition or seeking treatment for the same should consult their doctors before drinking red wine or any alcohol, as it can have counterproductive effects on their health.

Hero Image Credit: Kelsey Knight/Unsplash; Featured Image Credit: Rikkia Hughes/Unsplash

Read more:
Pop the cork to unlock the health benefits of red wine - Lifestyle Asia India

Brad Pitt is getting a taste of the beauty industry with a new skin care line that promises to help people age like fine wine.

The new line, Le Domaine, is a joint effort between Pitt and organic wine growers the Perrin family. The products include creams and serums and cost between $80 to $385 and come in small bottles made of recycled glass made with re-purposed parts of wine barrels.

Le Domaine purports to have uncorked the secret to slowing aging with a pair of exclusive, patented active ingredients. The first, GSM10, is made, in part, from a marc from grenache seeds and syrah seeds. The lines website says these ingredients work to stop collagen destruction, have antioxidant properties, and balance the skin.

The second, ProGR3, is said to reduce visible signs of aging by using natural molecules found in plant extracts, vine cuttings, chamomile, and green tea.

Though the line touts graceful aging benefits, Pitt interestingly debunked the idea that you can stop the clock in an interview.

I dont want to be running from aging, Pitt said while discussing the line with Vogue. Its a concept we cant escape, and I would like to see our culture embracing it a bit more, talking about it in those terms.

Ultimately, Dr. Viktoryia Kazlouskaya, a dermatologist with Khrom Dermatology, Brooklyn, N.Y., says approaches to physical signs of aging are as varied as tastes in wine. Some feel young inside and want their appearance to match that. Others see lines and wrinkles as signs of a well-lived life, and others prefer a blend.

Either approach reflects the expression of the authentic self, as authenticity means different things for different people, Kazlouskaya says. There is no shame in a desire to match the inner energy with the outer, and anti-aging practices will stay with us for the years ahead.

But will Pitts new foray into beauty help people who want to slow the signs of aging? Heres what dermatologists and researchers say.

Pitts active ingredients are new. But some of the components of them, like the syrah seeds, are inspired by wine.

Wine, particularly red, has a reputation for providing some health benefits, including to the skin. But the recent evidence is contradictory.

In fact, research from 2019 indicated that drinking wine could increase signs of facial aging, including undereye puffiness. However, the plant compound resveratrol, found in red wine, may help fight cell damage, an older 2010 review suggested.

But what about the topical use of some of these ingredients?

Lets start with those found in GSM10. Though no peer-reviewed studies exist on it, one expert says the gape seed extract may have some promise.

Grape seeds are known to be rich in polyphenols which are molecules that have antioxidant and anti-inflammatory properties, says Dr. Emily Wood, a board certified dermatologist, at Westlake Dermatology in Austin.

A 2020 review pointed to research that grapeseed extracts had anti-inflammatory properties and might have benefits that support aging gracefully. An older 2011 study of mice indicated that grape seed extract might reduce sun damage, a key trigger for premature aging.

Similarly, the components of ProGR3 do have some research behind them.

A pair of smaller studies one from 2005 and another from 2013 suggest green tea extract could slow skin aging.

A 2010 study indicated chamomile oil application could reduce atopic dermatitis in mice, while one from 2018 suggested application could aid wound healing. Though neither study on chamomile mentioned aging, one expert believes that, like green tea, the properties suggest it could help.

Both green tea and chamomile address signs of aging topically and when ingested, says Dr. Reid Maclellan, the founder and CEO of Cortina, adjunct Faculty at Harvard Medical School, and director of Proactive Dermatology Group. Both teas are antioxidant-rich and within, have a biological compound called polyphenols which work to destroy free radicals and slow the progression of aging.

Maclellan says the decision to use vine cuttings may be because of the research behind resveratrol. Research, like a 2019 review, suggests it has antioxidant properties to slow photoaging and protect against oxidative damage, such as from UV radiation.

Could all of these components, combined, team up to fight the signs of aging? The jury is out.

The key question is whether or not these extracts are actually permeating the epidermis due to the fact that polyphenols are hydrophilic, and the top layer of the skin has a high lipid content, says Wood. Think of the simple kitchen experiment of mixing oil and water together. Similar principles are at play when we think of drug delivery to the skin. The vehicle of delivery is key when looking at achieving effective penetration.

As a consumer, Kazlouskaya understands the interest in the new line.

On an emotional level, I already see myself opening this beautifully designed box containing a classy-looking jar with a massive oak wood cap, she says.

But as a dermatologist, Kazlouskaya is trained to step back and look at the whole package mainly, the evidence behind the ingredients. Thats where shes not sold on the touted benefits of the new line. She says she wants to know:

Wood has similar thoughts. She loves the elegant packaging and the fact that its made from recycled materials. But she cant judge a product by its recycled wine barrel cover.

There is some solid science backing the idea of utilizing plant-derived polyphenols to decrease signs of aging, Wood says. However, more studies need to be conducted on the effectiveness of topical polyphenols and in which vehicles of delivery these molecules will effectively penetrate the epidermis.

Though aging is a natural process that cannot be stopped, experts say some of its effects can be slowed.

Though its not as easy as 1-2-3, Dr. Jeremy Fenton of Schweiger Dermatology Group in NYC has simplified his advice for patients looking for products that help reduce the signs of aging into a three-step process:

1. Sunscreen

2. Retinoid or retinol (if your skin can tolerate it)

3. Topical antioxidant products/serums

The American Academy of Dermatology Association recommends using a broad-spectrum sunscreen of at least SPF 30 or above and reapplying every two hours when exposed to the sun to protect against aging and skin cancer.

Research from 2019 suggests retinoid, a derivative of vitamin A, has skin care benefits, including anti-wrinkle properties.

Fenton says vitamins C and E are two of the antioxidant ingredients found in some serums and products he suggests patients look into.

A 2020 review suggests the use of vitamins C and E could also reduce the signs of aging.

Kazlouskaya agrees about sunscreen, retinol/retinoids, and antioxidants. Though there always seems to be a new ingredient or product on the block, she says less is often more.

I learned to be a minimalist after treating numerous patients with rosacea and sensitive skin, as more does not mean better, she says.

Read the rest here:
Brad Pitt's New Skin Care Line Inspired by Wine: What Experts Think - Healthline

New York dermatologist Doris Day, MD

Significant Changes:I increased hydration and added higher-gradepeptides.

Go-to Products:I am always testing products but ingredients Istick to include growth factors,antioxidants, resveratrol, retinol, niacinamide and hyaluronic acid. There are always new ingredients and formulas Im working on, right now Im looking at ones that help support and nourish a healthy skin biome.

Favorite Treatments:My go-to treatments include a Sofwave ultrasound skin tightening treatment twice a year, neuromodulator injections about three times a year and a little filler touch up once a year.

Best Advice:Sun protection every day. Youre never too old or too young to protect your skin. Also see a great dermatologist to make sure you have a plan to keep your skin healthy and beautiful. Finally, see a functional medicine doctor or gynecologist who specializes in hormone replacement. It will help preserve collagen in your skin, as well as reduce other risks of aging.

Continued here:
What 6 Over-50 Beauty Experts Do to Treat Their Own Skin - NewBeauty Magazine

There is no denying that wine has been an integral part of many peoples lives over the years. Moreover, the benefits associated with it have also been documented after research for a long time. R&D on red wine continues even now while suggesting that drinking it in moderation offers certain benefits. So, red wine, when consumed in moderation, is said to keep the heart healthy. There are certain substances present in the wine, especially antioxidants, that may help prevent coronary artery diseases that lead to heart attacks.

However, you must remember the fact that healthcare providers do not recommend drinking alcohol for your hearts benefit. There is no denying that too much alcohol is, of course, too much harmful for your body.

The antioxidants present in red wine called polyphenols help protect blood vessel linings in the heart. There is another polyphenol called resveratrol present in red wine that is known to benefit the hearts health.

Now, the question that arises here is whether red wine is healthy. Let us delve deeper into some of its benefits.

If you drink red wine, it may lower the risk of cardiovascular diseases. The antioxidants called polyphenols in red wine keep the blood vessels flexible by preventing unwanted clotting in your heart.

According to studies, people who consume red wine three to four times a week are 30% less prone to developing diabetes compared to those who drink it for less than a week. The polyphenols in red wine may help control blood sugar levels.

As mentioned earlier, resveratrol is a significant ingredient present in red wine that may help destroy malignant cells in the body. It also helps protect normal tissues from getting destroyed due to the radiation that is given to cancer patients.

Consuming wine helps convert bad fats to calorie-burning brown fats. Wine is known to combat obesity as it helps increase the metabolic rate in the body.

Wine is known to lower blood pressure as it increases nitric oxide levels in the blood. It also helps you get relief from stress and prevents high blood pressure.

As mentioned above, no health expert will ever recommend you to have red wine to prevent heart diseases or regulate any health issues in your body. It is because alcohol is addictive and can even worsen your health problems. So, if you want to consume red wine, try to have it in moderation with an experts advice.

More:
Red Wine: Is it really healthy? Find out - Web News Observer