Resveratrol, pterostilbene and your skin
Antioxidant, anti-inflammatory, lipolytic, anti-ageing, cellulite
Resveratrol, found in black/purple grapes, red wine, blueberries and several other plants is one of the most well-known anti-ageing actives known today, and shares similar properties to its chemical analog, pterostilbene (also found in purple/black grapes, blueberries etc). Both have been found in numerous studies to be powerful antioxidants, anti-inflammatory and lipolytic actives and to reduce pigmentation, but above all they are known for their anti-ageing action, based on sirtuin (SIRT1) enhancement.
Pterostilbene and resveratrol cream
For all those reasons, resveratrol and pterostilbene are of great importance as active ingredients in anti-ageing, anti-cellulite, leg wellness, skin lightening and under-eye creams [the Celluence® creams are the only leg wellness / cellulite creams in the world with high concentrations of 95%+ pure resveratrol and 95%+ pure pterostilbene, plus 38x other natural anti-cellulite actives].
8+ ways Resveratrol & pterostilbene
boost skin healing and fight free radical damage, inflammation, ageing and cellulite
Protective molecular mechanisms of Resveratrol in UVR induced Skin carcinogenesis.
Abstract: Skin cancer is a major health problem worldwide. It is the most common cancer in the United States and poses a significant healthcare burden. Excessive UVR exposure is the most common cause of skin cancer. Despite various precautionary measures to avoid direct UVR exposure, the incidence of skin cancer and mortality related to it remains high. Furthermore, the current treatment options are expensive and have side effects including toxicity to normal cells. Thus, a safe and effective approach is needed to prevent and treat skin cancer. Chemopreventive strategy by using naturally occurring compounds, such as resveratrol, is a promising approach to reduce the incidence of UVR-induced skin cancer and delay its progression. This review highlights the current body of evidence related to chemopreventive role of resveratrol and its molecular mechanisms in UVR induced skin carcinogenesis. This article is protected by copyright. All rights reserved.
Chronic topical application of resveratrol accelerates wound healing...
...with improved epidermis, collagen deposition and improved vascularization of wound beds in young skin, due to stimulation of the AMPK pathway, the key mediator of wound healing. In aged skin, however, only metformin, a much stronger caloric restriction mimetic than resveratrol, was effective (in aged skin, AMPK pathway is inhibited, correlating with impaired vasculature and reduced healing ability)
[Source: Anti-aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application]
Resveratrol fights MITOCHONDRIAl-dysfunction related CONDITIONS...
...by protecting mitochondria from oxidative stress, by helping regulate their metabolism and biogenesis and by modulating cell apoptosis due to mitochondrial dysfunction [Source: Dietary Polyphenols and Mitochondrial Function: Role in Health and Disease]
Resveratrol, together with genistein and EGCG, inhibits preadipocyte differentiation...
...at low dosages in an additive manner (but not synergistically). The combination reduces levels of PPAR-gamma and C/EBP-alpha the two key preadipocyte differentiation regulators. The combination also reduced FABP4 and perilipin, two PPAR-γ/C/EBP-α downstream molecules. The individual compounds had no anti-adipogenic effect at low concentrations.
[Source: Antiadipogenic Effects and Mechanisms of Combinations of Genistein, Epigallocatechin-3-Gallate, and/or Resveratrol in Preadipocytes]
Resveratrol decreases lipid accumulation in adipocytes...
...by inhibiting PPAR-gamma, C/EBPs and their target genes (FAS, aP2, SCD-1, and LPL) Resveratrol, the phytochemical found in red wine, berries and other foods and considered responsible for their anti-ageing qualities, is known to trigger fat release from fat cells (lipolysis). Resveratrol exerts both it's anti-ageing and it's anti-obesity effect by activating a protein called sirtuin (SIRT1). SIRT1 is a major target of anti-ageing strategies and now scientists have found that SIRT1 also stimulates fat release.
Sirtuin, and subsequently resveratrol, does that by: increasing another protein found in fat cells, called ATGL. ATGL (adipocyte trigluceride lipase) is well-known for it's stimulation of fat release; inhibiting a protein called PPAR-gamma, one of the most important triggers of fat accumulation
Now that the mechanism of action of resveratrol is clarified, applications of this natural, healthful chemical on anti-cellulite and anti-aging creams is further warranted.
Abstract: To investigate whether sirtuin 1 (Sirt1) could affect the transcriptional expression of the adipose triglyceride lipase (ATGL) gene, we treated porcine adipocytes with the general Sirt1 activator resveratrol (RES) with the Sirt1 inhibitor nicotinamide (NAM) or a knockdown of Sirt1 by Sirt1-specific small interfering RNA (siRNA). The RES (50 μM) activated Sirt1 gene expression and increased ATGL gene expression and glycerol release (P < 0.01). The Sirt1 inhibitor NAM or knockdown with Sirt1 siRNA further proved that the ATGL mRNA abundances were decreased (P < 0.05) after inhibition with Sirt1 in adipocytes. Furthermore, we found the opposite Sirt1 regulation pattern for PPARγ to that of ATGL in adipocytes. In summary, Sirt1 regulates the transcriptional expression of ATGL in adipocytes, and PPARγ appears to have an important role in this process. These results add to our understanding of the role of Sirt1 in adipose mobilization.
[Source: Sirtuin1 affects the transcriptional expression of adipose triglyceride lipase in porcine adipocytes]
Resveratrol fights fat accumulation...
...by inhibiting PPAR-gamma, FAS, LPL and other adipogenic factors.
Resveratrol (3,4,5-trihydroxy-trans-stilbene), a phytoalexin found in grape skin, grape products, and peanuts as well as red wine, has been reported to have various biological and pharmacological properties. The purpose of this study was to investigate the anti-obesity effect of resveratrol-amplified grape skin extracts on adipocytes. The anti-obesity effects of grape skin extracts were investigated by measuring proliferation and differentiation in 3T3-L1 cells. The effect of grape skin ethanol extracts on cell proliferation was detected by the MTS assay. The morphological changes and degree of adipogenesis of preadipocyte 3T3-L1 cells were measured by Oil Red-O staining assay. Treatment with extracts of resveratrol-amplified grape skin decreased lipid accumulation and glycerol-3-phosphate dehydrogenase activity without affecting 3T3-L1 cell viability. Grape skin extract treatment resulted in significantly attenuated expression of key adipogenic transcription factors, including peroxisome proliferator-activated receptor, CCAAT/enhancer-binding proteins, and their target genes (FAS, aP2, SCD-1, and LPL). These results indicate that resveratrol-amplified grape skin extracts may be useful for preventing obesity by regulating lipid metabolism.
[Source: Anti-obesity effect of resveratrol-amplified grape skin extracts on 3T3-L1 adipocytes differentiation]
Resveratrol fights ageing by boosting the activity of SIRT1
Resveratrol is a well-known anti-ageing and slimming natural compound and is one of the molecules associated with the anti-ageing effects of red wine (the "French paradox").
Now scientists in Hong Kong have found that resveratrol reduces stem cell decline and significantly extends life span in mice suffering from premature ageing (progeria), by helping bind a protein called Lamin A onto SIRT1, the "longevity" gene. By boosting the activity of the longevity gene, resveratrol helps fight ageing.
Resveratrol is an ideal anti-ageing and anti-cellulite cream active ingredient. It is more and more widely used as an anti-ageing supplement and is an ideal ingredient in anti-ageing creams. In addition, resveratrol has been shown to halt the growth of new fat cells (adipogenesis), on it's own and when combined with other natural substances, such as the phytoestrogen genistein.
Abnormal splicing of LMNA gene or aberrant processing of prelamin A results in progeroid syndrome. Here we show that lamin A interacts with and activates SIRT1. SIRT1 exhibits reduced association with nuclear matrix (NM) and decreased deacetylase activity in the presence of progerin or prelamin A, leading to rapid depletion of adult stem cells (ASCs) in Zmpste24(-/-) mice. Resveratrol enhances the binding between SIRT1 and A-type lamins to increases its deacetylase activity. Resveratrol treatment rescues ASC decline, slows down body weight loss, improves trabecular bone structure and mineral density, and significantly extends the life span in Zmpste24(-/-) mice. Our data demonstrate lamin A as an activator of SIRT1 and provide a mechanistic explanation for the activation of SIRT1 by resveratrol. The link between conserved SIRT1 longevity pathway and progeria suggests a stem cell-based and SIRT1 pathway-dependent therapeutic strategy for progeria.
[Source: Resveratrol rescues SIRT1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria]
resveratrol protects fat cells from inflammation, helps fight cellulite
Dietary phytochemicals called polyphenols are known potent antioxidants that protect body tissues from free radical damage and consequent inflammation. Inflammation and oxidative damage are key components of cellulite, as well as diabetes and several other so-called civilisation diseases, such as heart disease and arthritis.
Recent research has now looked into 28 polyphenols (such as hesperidin, resveratrol, epigallocatechin gallate and curcumin) and concluded that those polyphenols protect fat cells from both oxidative damage and inflammation, by reducing inflammatory hormones, such as IL-6.
This practically means that orally taken polyphenols (either as foods or as supplements) can be used in the fight against fat tissue inflammation for the prevention of diabetes and cellulite. Polyphenols may also be used with local application in the fight against cellulite as active ingredients in an anti-cellulite cream. Naturally, the more of those polyphenols are present in the cream the better results are to be expected, due to a synergistic effect of using multiple ingredients.
Abstract: "Obesity has been associated with a marked risk of metabolic diseases and requires therapeutic strategies. Changes in redox status with increased oxidative stress in adipose tissue have been linked with obesity-related disorders. Thus, the biological effect of antioxidants such as polyphenols is of high interest. We aimed to measure antioxidant capacities of 28 polyphenols representative of main dietary phenolic acids, flavonoids, stilbenes and curcuminoids. Then, 14 molecules were selected for the evaluation of their effect on 3T3-L1 preadipocytes and human red blood cells exposed to oxidative stress. Analysis of reducing and free radical-scavenging capacities of compounds revealed antioxidant properties related to their structure, with higher activities for flavonoids such as quercetin and epicatechin. Their effects on preadipocytes' viability also depended on their structure, dose and time of exposure. Interestingly, most of the compounds exhibited a protective effect on preadipocytes exposed to oxidative stress, by reversing H₂O₂-induced anti-proliferative action and reactive oxygen species production. Polyphenols also exerted an anti-inflammatory effect on preadipocytes exposed to H₂O₂ by reducing IL-6 secretion. Importantly, such antioxidant and anti-inflammatory effects were observed in co-exposition (polyphenol and prooxidant during 24 h) or pretreatment (polyphenol during 24 h, then prooxidant for 24 h) conditions. Moreover, compounds protected erythrocytes from AAPH radical-induced lysis. Finally, these results led to demonstrate that antioxidant and anti-inflammatory properties of polyphenols may depend on structure, dose, time of exposure and cell conditioning with oxidative stress. Such findings should be considered for a better understanding of polyphenols' benefits in strategies aiming to prevent obesity-related diseases."
[Source: Evaluation of antioxidant properties of major dietary polyphenols and their protective effect on 3T3-L1 preadipocytes and red blood cells exposed to oxidative stress]
Cocoa, berries and red wine
Sirtuins are a group of body chemicals known for their anti-aging / longevity benefits, and the mast few years more and more studies examine their action against fat accumulation / overweight.
In this new paper, published last week, it was shown that "SIRT1 acts as a crucial repressor of adipogenesis", i.e. SIRT1 stops the growth of new fat cells (contrary to the urban myth, the body continuously creates new fat cells as old ones die off). By halting the growth of new fat cells, it is possible to reduce adiposity and lose weight, as the excess fat is directed towards oxidation ("fat burning") by the body.
Other studies in the past have shown that resveratrol and pterostilbene may also have a direct lipolytic / thermogenic action on fat cells. In fact resveratrol and pterostilbene are also used in quality cellulite creams, due to their direct lipolytic action and their activity against fat cell growth and fat accumulation. Creams with high concentrations of these two chemicals are needed to replicate the amounts of resveratrol and pterostilbene used in studies.
Losing weight with resveratrol and pterostilbene
Of course, taking resveratrol or pterostilbene supplements or eating loads of blueberries is not a license to eat anything you fancy and expect to lose or not put on weight. In the end the excess calories will stimulate adipogenic (fattening) chemicals in the body which are much stronger than SIRT1. Between insulin and SIRT1, for example, insulin wins hands-down.
But if you follow a healthy diet and you exercise, SIRT1-stimulating foods and supplements, i.e. foods and supplements rich in resveratrol and pterostilbene, will help you make the most of your weight loss effort and and improve your overall health in the process.
Furthermore, continuous, lifelong consumption of SIRT1-stimulating foods, or resveratrol and pterostilbene supplements, may also help keep you younger for longer (SIRT1 is more known for it's longevity/anti-ageing properties than for it's anti-adipogenic action).
Of course, getting the majority of your resveratrol and pterostilbene from red wine and dark chocolate is not the same as getting it from blackberries and cocoa powder-enriched shakes and smoothies. So don't get too excited about indulging in wine and chocolate in order to stay young and lose weight!
- Paper: SIRT1 suppresses adipogenesis by activating Wnt/β-catenin signaling in vivo and in vitro
- Abstract: Sirtuin 1 (SIRT1) regulates adipocyte and osteoblast differentiation. However, the underlying mechanism should be investigated. This study revealed that SIRT1 acts as a crucial repressor of adipogenesis. RNA-interference-mediated SIRT1 knockdown or genetic ablation enhances adipogenic potential, whereas SIRT1 overexpression inhibits adipogenesis in mesenchymal stem cells (MSCs). SIRT1 also deacetylates the histones of sFRP1, sFRP2, and Dact1 promoters; inhibits the mRNA expression of sFRP1, sFRP2, and Dact1; activates Wnt signaling pathways; and suppresses adipogenesis. SIRT1 deacetylates β-catenin to promote its accumulation in the nucleus and thus induces the transcription of genes that block MSC adipogenesis. In mice, the partial absence of SIRT1 promotes the formation of white adipose tissues without affecting the development of the body of mice. Our study described the regulatory role of SIRT1 in Wnt signaling and proposed a regulatory mechanism of adipogenesis.
- Link: https://www.ncbi.nlm.nih.gov/pubmed/27776347
Resveratrol is not an "antioxidant"
Resveratrol is a well-known anti-ageing plant molecule, contained in grapes, berries and red wine, among other foods. Resveratrol works by increasing a protein called SIRT1, which improves lifespan and overall health and fights fat accumulation. But most importantly, resveratrol was thought to work as an "antioxidant".
However, this new study published this week shows that resveratrol does not act as an antioxidant. Instead it acts in quite the opposite way, as a pro-oxidant. The researchers have found that by being slightly poor-oxidant, resveratrol stimulates the body to boost it's antioxidant defences and produce more glutathione, one of the body's own powerful antioxidants.
Resveratrol is "hormetic"
Resveratrol achieves this effect by stimulating a protein called Nrf2, which is known to stimulate the body's own antioxidant defences. In fact, more and more papers, published the last few months, show that previously thought antioxidant molecules actually act as pro oxidants, by stimulating the same process, mediated by the protein Nrf2. nudge
The process by which a little bit of negative stimulation leads to positive changes in the body is called hormesis, a Greek work which means "gaining momentum". So by getting a bit of negative stimulation (mild free radical damage) that body is gently nudged, it gains momentum, to get much more efficient in fighting free radical damage.
- Paper: Hormetic shifting of redox environment by pro-oxidative resveratrol protects cells against stress.
- Abstract: Resveratrol has gained tremendous interest owing to multiple reported health-beneficial effects. However, the underlying key mechanism of action of this natural product remained largely controversial. Here, we demonstrate that under physiologically relevant conditions major biological effects of resveratrol can be attributed to its generation of oxidation products such as reactive oxygen species (ROS). At low nontoxic concentrations (in general <50µM), treatment with resveratrol increased viability in a set of representative cell models, whereas application of quenchers of ROS completely truncated these beneficial effects. Notably, resveratrol treatment led to mild, Nrf2-specific gene expression reprogramming. For example, in primary epidermal keratinocytes derived from human skin this coordinated process resulted in a 1.3-fold increase of endogenously generated glutathione (GSH) and subsequently in a quantitative reduction of the cellular redox environment by 2.61mVmmol GSH per g protein. After induction of oxidative stress by using 0.78% (v/v) ethanol, endogenous generation of ROS was consequently reduced by 24% in resveratrol pre-treated cells. In contrast to the common perception that resveratrol acts mainly as a chemical antioxidant or as a target protein-specific ligand, we propose that the cellular response to resveratrol treatment is essentially based on oxidative triggering. In physiological microenvironments this molecular training can lead to hormetic shifting of cellular defense towards a more reductive state to improve physiological resilience to oxidative stress.
Broad-spectrum protection against fight tissue inflammation - and cellulite
Pterostilbene, is an anti-ageing phytochemical primarily found in berries and grapes. It is closely related to another well-known anti-ageing chemical, resveratrol (the secret behind the so-called "French paradox"). Based on animal studies, both resveratrol and pterostilbene are thought to exhibit anti-cancer, anti-inflammatory and anti-ageing properties.
In this study it was discovered that pterostilbene (and the phytochemical garcinol) has a specific anti-inflammatory action on adipocytes (fat cells), reducing almost all important inflammatory markers: COX-2, iNOS, IL-6, and IL-1β and IL-6!
This is important news for cellulite reduction, as fat tissue inflammation is an important aspect of cellulite, and pterostilbene may be used in the fight against cellulite as an anti-cellulite cream ingredient, or to a lesser extent as a nutritional supplement ingredient.
- Paper: The inhibitory effect of pterostilbene on inflammatory responses during the interaction of 3T3-L1 adipocytes and RAW 264.7 macrophages, http://www.ncbi.nlm.nih.gov/pubmed/23268743
- Abstract: Chronic inflammation is characterized by the upregulation of proinflammatory cytokines in obese adipose tissue. Accumulations of adipose tissue macrophages enhance a chronic inflammatory state in adipose tissues. Many studies have indicated that the adipocyte-related inflammatory response in obesity is characterized by an enhanced infiltration of macrophages. The aim of this work was to study the inhibitory effects of garcinol and pterostilbene on the change in inflammatory response due to the interaction between 3T3-L1 adipocytes and RAW 264.7 macrophages. In the TNF-α-induced 3T3-L1 adipocyte model, garcinol and pterostilbene significantly decreased the mRNA expression of COX-2, iNOS, IL-6, and IL-1β and IL-6 secretion by suppressing phosphorylation of p-IκBα and p-p65. In a coculture model of 3T3-L1 adipocytes and RAW 264.7 macrophages, pterostilbene suppressed IL-6 and TNF-α secretion and proinflammatory mRNA expression and also reduced the migration of macrophages toward adipocytes. In the RAW 264.7 macrophage-derived conditioned medium (RAW-CM)-induced 3T3-L1 adipocyte and 3T3-CM-induced RAW 264.7 macrophage models, pterostilbene significantly decreased IL-6 and TNF-α secretion and proinflammatory mRNA expression (COX-2, iNOS, IL-6, TNF-α, PAI-1, CRP, MCP-1, resistin, and leptin). Our findings suggest that garcinol and pterostilbene may provide novel and useful applications to reduce the chronic inflammatory properties of adipocytes. We also found that pterostilbene inhibits proinflammatory responses during the interaction between 3T3-L1 adipocytes and RAW 264.7 macrophages.
- Resveratrol is a natural chemical found in red/black grapes, berry fruit and red wine, and is considered as one of the reasons behind the "French paradox", i.e. the reduced incidence of cardiovascular disease in France, despite high fat consumption (garlic being the other).
- Indeed, resveratrol has been found in this recently published research paper to be effective in reducing the inflammatory protein TNF-alpha in blood vessels of coronary artery disease patients with angina
- Resveratrol also reduced the number of blood vessel inner wall particles in the bloodstream, demonstrating a reduction in endothelial (inner wall) damage.
- The citrus extract quercetin, which also has blood vessel wall protective properties, did not show to have a similar effect against TNF-alpha
- The amount of resveratrol used in this clinical trial on 93 patients was 100mg/day, which is a modest nutritional supplementation amount
- Several brands offer 100mg supplements with high quality resveratrol at reasonable prices, so it is easy to benefit from this natural chemical, in an economic fashion (always please ask doctor's approval first)
- On the other hand, it is very difficult to receive this amount just by eating berries and grapes, and of course we would not recommend consuming 50 litres of pinot noir a day (2mg/lt) or 10 litres of selected Spanish wines / grape juice (10mg/lt) to achieve that amount.
- In addition to it's cardio protective action, resveratrol is an important, widely researched anti-ageing molecule which is also used in high quality anti-ageing and anti-cellulite creams
- Source: Resveratrol more effectively than quercetin reduces endothelium degeneration and level of necrosis factor α in patients with coronary artery disease.
- Abstract: INTRODUCTION: Endothelial dysfunction (ED) is one of the most important links in the pathogenesis of atherosclerosis (ASVD) - morphological basis of coronary artery disease (CAD). OBJECTIVE: to study the effect of polyphenolic antioxidants, resveratrol and quercetin, on endothelial degeneration factors in CAD patients. MATERIALS AND METHODS: The study involved 93 patients with coronary artery disease: stable angina pectoris, FC II. The cytofluorometric technique was applied to define the level of circulating endothelial microparticles (EMP) CD32+CD40+ in peripheral blood in order to identify ED. The content of tumor necrosis factor α (TNF-α), fibrinogen, hemocoagulation and lipid profile parameters were being determined in the blood, as well. Patients were divided into 3 groups. Basic therapy (β-blockers, statins, aspirin) was prescribed to 33 persons of the comparison group, patients of the study group 1 (30 persons) additionally received resveratrol at a dose of 100 mg daily, patients of the study group 2 (30 persons) got quercetin at a dose of 3 g per day. In 2 months, the second examination of the patients was performed in the amount indicated. RESULTS: under the influence of resveratrol a significant reduction of the level of TNF-α and the number of EMP in peripheral blood was shown, in contrast to the results of other study groups. All groups showed a decrease in total cholesterol and low-density lipoprotein cholesterol, statistical differences between data of groups were not found. Indicators of coagulogramma in all study groups did not change significantly, however, there was a statistically significant reduction of fibrinogen in the blood. CONCLUSIONS: Resveratrol, unlike quercetin, has a positive effect on the endothelial function and systemic inflammation, which may be the result of its influence on intracellular molecular cascades associated with the nuclear transcription factor of NF-kB.
- Dietary polyphenols are beneficial plant chemicals found in fruit, herbs and vegetables, which are known primarily from their antioxidant action
- Most importantly, however, different polyphenols also exert anti-inflammatory, anti-cancer, metabolic and anti-obesity action on the human body
- In fact, scientists now know that it is not the antioxidant action that is important in polyphenols but the action on inflammation and metabolism
- EGCG (from green tea), resveratrol (found in berries), quercetin (found in onions), curcumin (from turmeric), catechins (in cocoa), epicatechins (in pine bark and grape seeds), proanthocyanidins (e.g. in cranberries), and myricetin (found in fruit) are some of the most "famous" polyphenols
- A review published in 2014 reports that thousands of cell, tissue, animal and human studies in the last few years have shown the beneficial effects of polyphenols on health, and specifically in metabolic disorders and obesity
- Cell studies show that dietary polyphenols fight fat in multiple ways. They:
- Reduce the life span of adipocytes (fat cells)
- Reduce fat cell growth
- Inhibit the capacity of fat cells to accumulate fat
- Reduce fat cell proliferation
- Stimulate lipolysis (fat breakdown and release from fat cells)
- Boost energy expenditure / fat oxidation ("fat burning") outside fat cells
- Stimulate thermogenesis (fat burning inside fat cells)
- Inhibit adipose tissue inflammation within and outside adipose tissue
- Fight oxidative damage within and outside fat tissue
- Fight metabolic dysfunction within and outside adipose tissue
- Reduce high glucose levels, triglycerides, cholesterol and glycation
- "Animal studies strongly suggest that commonly consumed polyphenols have a pronounced effect on obesity as shown by lower body weight, fat mass and triglycerides through enhancing energy expenditure and fat utilization, and modulating glucose homeostasis"
- "On the other hand, human studies are more limited and are more inconsistent about the anti-obesity impact of dietary polyphenols probably due to the various study designs and lengths, variation among subjects (age, gender, ethnicity), chemical forms of the dietary polyphenols used and confounding factors such as other weight-reducing agents", the study authors state
- However, our experience of reviewing such studies in the last decade shows that polyphenols are more effective on cell cultures, tissues and animals are more effective simply because of the much higher dosage than used on humans, which is quite often one or two orders of magnitude greater
- Nevertheless, the general trend with the use of polyphenols in human trials is towards a healthier metabolic profile and reduced fat accumulation, obesity and it's complications, even with normal, dietary intakes or with reasonably increased intakes in the form of supplements etc.
- However, polyphenols could be much more beneficial at local level, i.e. for spot fat / cellulite reduction than it is for whole body level. This is because whole body weight loss depends too much on food intake and exercise and because very high intake of polyphenols at whole body level is practically impossible and possibly unhealthy
- Clearly, high-concentration topical application, similar to that seen in cell, tissue and animal studies makes much more sense, and is a trend seen in quality cosmeceuticals recently, including anti-ageing and cellulite creams
- In all cases, more "randomised controlled trials are warranted to reconcile the discrepancies between preclinical efficacies and inconclusive clinic outcomes of these polyphenols", as the study authors report.
- Source: Novel insights of dietary polyphenols and obesity.
- Abstract: The prevalence of obesity has steadily increased over the past three decades both in the United States and worldwide. Recent studies have shown the role of dietary polyphenols in the prevention of obesity and obesity-related chronic diseases. Here, we evaluated the impact of commonly consumed polyphenols, including green tea catechins, especially epigallocatechin gallates, resveratrol and curcumin, on obesity and obesity-related inflammation. Cellular studies demonstrated that these dietary polyphenols reduce viability of adipocytes and proliferation of preadipocytes, suppress adipocyte differentiation and triglyceride accumulation, stimulate lipolysis and fatty acid β-oxidation, and reduce inflammation. Concomitantly, the polyphenols modulate signaling pathways including the adenosine-monophosphate-activated protein kinase, peroxisome proliferator activated receptor γ, CCAAT/enhancer binding protein α, peroxisome proliferator activator receptor gamma activator 1-alpha, sirtuin 1, sterol regulatory element binding protein-1c, uncoupling proteins 1 and 2, and nuclear factor-κB that regulate adipogenesis, antioxidant and anti-inflammatory responses. Animal studies strongly suggest that commonly consumed polyphenols described in this review have a pronounced effect on obesity as shown by lower body weight, fat mass and triglycerides through enhancing energy expenditure and fat utilization, and modulating glucose hemostasis. Limited human studies have been conducted in this area and are inconsistent about the antiobesity impact of dietary polyphenols probably due to the various study designs and lengths, variation among subjects (age, gender, ethnicity), chemical forms of the dietary polyphenols used and confounding factors such as other weight-reducing agents. Future randomized controlled trials are warranted to reconcile the discrepancies between preclinical efficacies and inconclusive clinic outcomes of these polyphenols.
- Resveratrol, found in grapes, berries and red wine) and curcumin (found in turmeric) are proven anti-inflammatory, antioxidant and anti-ageing natural molecules, but heir absorption and instability limit their clinical use.
- Liposomal and other enhanced absorption and stability forms are already sued in supplements and cosmetics with the combination of the two natural chemicals providing synergistic results.
- Now scientists have created hybrids of curcumin and resveratrol which possess increased anti-inflammatory activity and proved their efficacy on acute lung injury, hoping that these compounds can lead to the development of new drugs against inflammatory conditions.
- In the meantime, the stabilised forms of high purity resveratrol and curcumin already provide valuable anti-ageing, anti-inflammatory and antioxidant benefits in a group of select skin care products, if used in high concentrations.
- Source: Development of resveratrol-curcumin hybrids as potential therapeutic agents for inflammatory lung diseases.
- Abstract: Acute lung injury (ALI) is a major cause of acute respiratory failure in critically-ill patients. Resveratrol and curcumin are proven to have potent anti-inflammatory efficacy, but their clinical application is limited by their metabolic instability. Here, a series of resveratrol and the Mono-carbonyl analogs of curcumin (MCAs) hybrids were designed and synthesized by efficient aldol construction strategy, and then screened for anti-inflammatory activities in vitro and in vivo. The results showed that the majority of analogs effectively inhibited the LPS-induced production of IL-6 and TNF-α. Five analogs, a9, a18, a19, a20 and a24 exhibited excellent anti-inflammatory activity in a dose-dependent manner along with low toxicity in vitro. Structure activity relationship study revealed that the electron-withdrawing groups at meta-position and methoxyl group (OCH3) at the para position of the phenyl ring were important for anti-inflammatory activities. The most promising compound a18 decreased LPS induced TNF-α, IL-6, IL-12, and IL-33 mRNA expression. Additionally, a18 significantly protected against LPS-induced acute lung injury in the in vivo mouse model. The research of resveratrol and MCAs hybrids could bring insight into the treatment of inflammatory diseases and compound a18 may serve as a lead compound for the development of anti-ALI agents.
- In a new study published yesterday it was found that the humble dandelion (taraxacum official) is very effective in causing apoptosis in human visceral pre-adipocytes (abdominal "baby" fat cells)
- On the other hand DHA, on the the two main omega-3 fatty acids in fish oil, caffeine and the berry extract resveratrol, we more effective in reducing fat accumulation in fat cells
- Caffeine, DHA and the olive leaf extract oleuropein were more effective in boosting fat reduction (lipolysis) in pre-adipocytes ("baby" fat cells)
- On the other hand, oleuropein, bitter orange and dandelion were more effective lipolytic agents in mature fat cells
- Finally caffeine inhibited adipogenesis in pre-adipocytes, i.e. it inhibited the growth of baby fat cells
- In summary, the most effective overall natural slimming chemicals that were assessed in this study were dandelion, caffeine and DHA, with resveratrol, oleuropein and bitter orange, also contributing to fat reduction
- This limited study only assessed 8 natural chemicals, out of hundreds with proven activities in lipolysis, adipogenesis, apoptosis etc, so a much more broad comparative study of natural slimming agents is warranted
- Source: Different anti-adipogenic effects of bio-compounds on primary visceral pre-adipocytes and adipocytes.
- Abstract: Several natural compounds exhibit strong capacity for decreasing triglyceride accumulation, enhancing lipolysis and inducing apoptosis. The present study reports the anti-adipogenic effects of Silybum marianum (SL), Citrus aurantium (CA), Taraxacum officinale (TO), resveratrol (RE), Curcuma longa (CU), caffeine (CF), oleuropein (OL) and docosahexaenoic acid (DHA) in reducing differentiation and increasing lipolysis and apoptosis. Analyses were performed on human primary visceral pre-adipocytes after 10 (P10) and 20 (P20) days of treatment during differentiation and on mature adipocytes after 7 days of treatment (A7). The percentage of apoptosis induced by TO extract in P10 and P20 cells was significantly higher than that induced by all other compounds and in CTRL cells. Triglyceride accumulation was significantly lower in cells treated with DHA, CF, RE in comparison to cells treated with OL and in CTRL cells. Treatments with CF, DHA and OL significantly incremented lipolysis in P20 cells in comparison to other compounds and in CTRL cells. On the contrary, the treatment of A7 cells with OL, CA and TO compounds significantly increased cell lipolysis. The addition of CF in differentiating P20 pre-adipocytes significantly increased the expression of genes involved in inhibition of adipogenesis, such as GATA2, GATA3, WNT1, WNT3A, SFRP5, and DLK1. Genes involved in promoting adipogenesis such as CCND1, CEBPB and SREBF1 were significantly down-regulated by the treatment. The screening of bioactive compounds for anti-adipogenic effects showed that in differentiating cells TO extract was the most effective in inducing apoptosis and CF and DHA extracts were more efficient in inhibition of differentiation and in induction of cell lipolysis.
- Comment: Most people think that resveratrol, the active ingredient in blueberries and red wine, is an antioxidant itself. This paper suggests that resveratrol is a mild pro-oxidant instead, which stimulates the cell's Nrf-2 antioxidant capacity. This triggers cells to produce glutathione, the body's most potent detoxification and antioxidant chemical, which in turns fights oxidation and DNA damage.
- However, all the latest research agrees with this finding: polyphenols and carotenoids do not act as antioxidant themselves inside the body, they instead act either as anti-inflammtory or they trigger the Nrf-2 system which then boosts detoxification and antioxidant capacity.
- Source: Hormetic Shifting of Redox Environment by Pro-Oxidative Resveratrol Protects Cells Against Stress
- Abstract: Resveratrol has gained tremendous interest owing to multiple reported health-beneficial effects. However, the underlying key mechanism of action of resveratrol remained largely controversial. Here, we demonstrate that under physiologically relevant conditions major biological effects of resveratrol can be attributed to the generation of oxidation products such as reactive oxygen species (ROS). At low hormetic concentrations (< 50 µM), treatment with resveratrol increased cell viability in a set of representative cell models, whereas application of quenchers of ROS completely truncated these beneficial effects. Notably, application of resveratrol led to mild, Nrf2-specific cellular gene expression reprogramming. For example, in primary human epidermal keratinocytes this resulted in a 1.3-fold increase of endogenous metabolites such as glutathione (GSH) and subsequently in a quantitative reduction of the cellular redox environment by 2.61 mV mmol GSH per g protein. After external application of oxidative stress by using 0.8% (v/v) ethanol, endogenous generation of ROS was consequently reduced by 24% in resveratrol pre-treated cells. In contrast to the common perception that resveratrol acts mainly as a chemical antioxidant or as a target protein-specific ligand, we propose that effects from resveratrol treatment are essentially based on oxidative triggering of cells. In relevant physiological microenvironments this effect can lead to hormetic shifting of cellular defence towards a more reductive state to improve resilience to oxidative stress in a manner that can be exactly defined by the redox-environment of the cell.
- Source: Resveratrol: anti-obesity mechanisms of action
- Abstract: Resveratrol is a non-flavonoid polyphenol which belongs to the stilbenes group and is produced naturally in several plants in response to injury or fungal attack. Resveratrol has been recently reported as preventing obesity. The present review aims to compile the evidence concerning the potential mechanisms of action which underlie the anti-obesity effects of resveratrol, obtained either in cultured cells lines and animal models. Published studies demonstrate that resveratrol has an anti-adipogenic effect. A good consensus concerning the involvement of a down-regulation of C/EBPα and PPARγ in this effect has been reached. Also, in vitro studies have demonstrated that resveratrol can increase apoptosis in mature adipocytes. Furthermore, different metabolic pathways involved in triacylglycerol metabolism in white adipose tissue have been shown to be targets for resveratrol. Both the inhibition of de novo lipogenesis and adipose tissue fatty acid uptake mediated by lipoprotein lipase play a role in explaining the reduction in body fat which resveratrol induces. As far as lipolysis is concerned, although this compound per se seems to be unable to induce lipolysis, it increases lipid mobilization stimulated by β-adrenergic agents. The increase in brown adipose tissue thermogenesis, and consequently the associated energy dissipation, can contribute to explaining the body-fat lowering effect of resveratrol. In addition to its effects on adipose tissue, resveratrol can also acts on other organs and tissues. Thus, it increases mitochondriogenesis and consequently fatty acid oxidation in skeletal muscle and liver. This effect can also contribute to the body-fat lowering effect of this molecule.
- Source: Resveratrol directly affects in vitro lipolysis and glucose transport in human fat cells.
- Abstract: Resveratrol is a naturally occurring polyphenol found in many dietary sources and red wine. Recognized as a cancer chemoprevention agent, an anti-inflammatory factor and an antioxidant molecule, resveratrol has been proposed as a potential anti-obesity compound and to be beneficial in diabetes. Most of the studies demonstrating the anti-adipogenic action of resveratrol were performed as long-term treatments on cultured preadipocytes. The aim of this study was to analyse the acute effects of resveratrol on glucose uptake and lipolysis in human mature adipocytes. Samples of subcutaneous abdominal adipose tissue were obtained from overweight humans and immediately digested by liberase. Fat cells were incubated (from 45 min to 4 h) with resveratrol 1 μM-1 mM. Then, glycerol release or hexose uptake was determined. Regarding lipolysis, the significant effects of resveratrol were found at 100 μM, consisting in a facilitation of isoprenaline stimulation and an impairment of insulin antilipolytic action. At 1 and 10 μM, resveratrol only tended to limit glucose uptake. Resveratrol 100 μM did not change basal glucose uptake but impaired its activation by insulin or by benzylamine. This inhibition was not found with other antioxidants. Such impairment of glucose uptake activation in fat cells may led to a reduced availability of glycerol phosphate and then to a decreased triacylglycerol assembly. Therefore, resveratrol increased triacylglycerol breakdown triggered by β-adrenergic activation and impaired lipogenesis. Consequently, our data indicate that resveratrol can be considered as limiting fat accumulation in human fat cells and further support its use for the mitigation of obesity.
- Source: Promising therapeutic potential of pterostilbene and its mechanistic insight based on preclinical evidence.
- Abstract: Pterostilbene (PS) is a well-recognized antioxidant that primarily exists in blueberries, grapevines and heartwood of red sandalwood. Interest in this compound has been renewed in recent years, and studies have found that PS possesses an array of pharmacological properties, including chemopreventive, antiinflammatory, antidiabetic, antidyslipidemic, antiatherosclerotic and neuroprotective effects. However, the greater in vivo bioavailability of PS, as compared to resveratrol, is an added advantage for its efficacy. This review provides a summary regarding the sources, pharmacokinetic aspects and pharmacodynamics of PS, with a focus on the molecular mechanisms underlying its protective effects against cancer, brain injuries and heart disease. Studies regarding the safety profile of PS have also been included. Based on the presently available evidence, we conclude that PS represents an active phytonutrient and a potential drug with pleiotropic health applications.
- Source: Efficacy and Tolerability of a Skin Brightening/Anti-Aging Cosmeceutical Containing Retinol 0.5%, Niacinamide, Hexylresorcinol, and Resveratrol.
- Abstract: Consumers are increasingly interested in over-the-counter skin care products that can improve the appearance of photodamaged and aging skin. This 10-week, open-label, single- center study enrolled 25 subjects with mild to moderate hyperpigmentation and other clinical stigmata of cutaneous aging including fine lines, sallowness, lack of clarity, and wrinkling. Their mean age was 53.4±7.7 years. The test product contained retinol 0.5% in combination with niacinamide 4.4%, resveratrol 1%, and hexylresorcinol 1.1% in a moisturizing base. Subjects were provided a skin care regimen including a cleanser, hydrating serum, moisturizer, and an SPF 30 sunscreen for daily use. The test product was applied only at night. The use of this skin brightening/anti-aging cosmeceutical was found to provide statistically significant improvements in all efficacy endpoints by study end. Fine lines, radiance, and smoothness were significantly improved as early as week 2. By week 4, hyperpigmentation, overall skin clarity, evenness of skin tone, and wrinkles showed statistically significant improvement compared to baseline. Mild retinoid dermatitis including flaking and redness occurred early in the study as reflected by tolerability scores. By week 10, subjects reported no stinging, itching, dryness, or tingling. The results of this open-label clinical study suggest that a topical cream containing retinol 0.5% in combination with niacinamide, resveratrol, and hexylresorcinol is efficacious and tolerable for skin brightening/anti-aging when used with a complementary skin care regimen including SPF 30 sun protection.
- Source: The Effects of Resveratrol Supplementation in Overweight and Obese Humans: A Systematic Review of Randomized Trials.
- Abstract: BACKGROUND: Obesity and metabolic syndrome are significant global health issues, with current public health messages predominately focused on altering dietary and physical activity behaviors. Resveratrol is a polyphenol (stilbenoid) commonly found in grapes, and human trials to date have shown conflicting and limited beneficial effects with respect to health. The aim of this study was to determine the effect of resveratrol supplementation on reducing body weight and modifying associated inflammatory markers. METHODS: A systematic review was undertaken following the PRISMA guidelines and using five indexed databases (OVID MEDLINE, Cochrane Library, Web of Science, SCOPUS, and CINAHL). A search strategy was formulated to select randomized, double-blind, placebo-controlled human trials investigating the effects of resveratrol supplementation on obesity or overweight, including body weight, metabolic and inflammatory markers. RESULTS: Five thousand five hundred sixty-nine studies published from 1990 to November 2015 were identified, with only nine papers meeting the inclusion criteria. The studies involved 208 participants (aged 49.2 ± 8.3 years) and utilized a substantial range of resveratrol doses (75-3000 mg/day). Study durations were a minimum of 2 weeks (14-90 days). Seven studies indicated no significant change in body mass index or body weight (P > 0.05), and three studies showed no improvements in fat mass, fat volume, or abdominal fat distribution (P > 0.05). Four studies included measurements of inflammatory markers, with three of these finding resveratrol supplementation to have a significant positive effect (P > 0.05). CONCLUSION: Based on the included studies, there is currently insufficient evidence to support the recommendation of resveratrol supplements in management of obesity. However, there were significant but not entirely consistent anti-inflammatory effects after resveratrol supplementation in overweight and obese individuals.
- Metformin and resveratrol ameliorate muscle insulin resistance through preventing lipolysis and inflammation in hypoxic adipose tissue.
- Abstract: This study aims to investigate the effects of metformin and resveratrol on muscle insulin resistance with emphasis on the regulation of lipolysis in hypoxic adipose tissue. ICR mice were fed with high fat diet (HFD) for 10days with administration of metformin, resveratrol, or intraperitoneal injection of digoxin. Adipose hypoxia, inflammation and cAMP/PKA-dependent lipolysis were investigated. Moreover, lipid deposition and insulin resistance were examined in the muscle. Metformin and resveratrol attenuated adipose hypoxia, inhibited HIF-1α expression and inflammation in the adipose tissue of HFD-fed mice. Metformin and resveratrol inhibited lipolysis through prevention of PKA/HSL activation by decreasing the accumulation of cAMP via preserving PDE3B. Metformin and resveratrol reduced FFAs influx and DAG accumulation, and thus improved insulin signaling in the muscle by inhibiting PKCθ translocation. This study presents a new view of regulating lipid metabolism to ameliorate insulin resistance and provides the clinical guiding significance for obesity and type 2 diabetes with metformin and resveratrol treatment.
- Source: Phytochemicals in regulating fatty acid β-oxidation: Potential underlying mechanisms and their involvement in obesity and weight loss.
- Abstract: Excessive accumulation of fat as the result of more energy intake and less energy expenditure is known as obesity. Lipids are essential components in the human body and are vital for maintaining homeostasis and physiological as well as cellular metabolism. Fatty acid synthesis and catabolism (by fatty acid oxidation) are normal part of basic fuel metabolism in animals. Fatty acids are degraded in the mitochondria by a biochemical process called β-oxidation in which two-carbon fragments are produced in each cycle. The increase in fatty acid oxidation is positively correlated with body mass index. Although healthy life style, avoiding Western diet, dieting and strenuous exercise are the commonly used methods to lose weight, they are not considered a permanent solution in addition to risk attenuation of in basal metabolic rate (BMR). Pharmacotherapy offers benefits of weight loss by altering the satiety and lowering absorption of fat from the food; however, its side effects may outweigh the benefits of weight loss. Alternatively, dietary phytochemicals and natural health products offer great potential as an efficient weight loss strategy by modulating lipid metabolism and/or increasing BMR and thermogenesis. Specifically, polyphenols such as citrus flavonoids, green tea epigallocatechin gallate, resveratrol, capsaicin and curcumin, have been reported to increase lipolysis and induce fatty acid β-oxidation through modulation of hormone sensitive lipase, acetyl-coA carboxylase, carnitine acyl transferase and peroxisome proliferator-activated receptor gamma coactivator-1. In this review article, we discuss selected phytochemicals in relation to their integrated functionalities and specific mechanisms for weight loss.
- Source: Mood, stress and longevity: convergence on ANK3.
- Abstract: Antidepressants have been shown to improve longevity in C. elegans. It is plausible that orthologs of genes involved in mood regulation and stress response are involved in such an effect. We sought to understand the underlying biology. First, we analyzed the transcriptome from worms treated with the antidepressant mianserin, previously identified in a large-scale unbiased drug screen as promoting increased lifespan in worms. We identified the most robust treatment-related changes in gene expression, and identified the corresponding human orthologs. Our analysis uncovered a series of genes and biological pathways that may be at the interface between antidepressant effects and longevity, notably pathways involved in drug metabolism/degradation (nicotine and melatonin). Second, we examined which of these genes overlap with genes which may be involved in depressive symptoms in an aging non-psychiatric human population (n=3577), discovered using a genome-wide association study (GWAS) approach in a design with extremes of distribution of phenotype. Third, we used a convergent functional genomics (CFG) approach to prioritize these genes for relevance to mood disorders and stress. The top gene identified was ANK3. To validate our findings, we conducted genetic and gene-expression studies, in C. elegans and in humans. We studied C. elegans inactivating mutants for ANK3/unc-44, and show that they survive longer than wild-type, particularly in older worms, independently of mianserin treatment. We also show that some ANK3/unc-44 expression is necessary for the effects of mianserin on prolonging lifespan and survival in the face of oxidative stress, particularly in younger worms. Wild-type ANK3/unc-44 increases in expression with age in C. elegans, and is maintained at lower youthful levels by mianserin treatment. These lower levels may be optimal in terms of longevity, offering a favorable balance between sufficient oxidative stress resistance in younger worms and survival effects in older worms. Thus, ANK3/unc-44 may represent an example of antagonistic pleiotropy, in which low-expression level in young animals are beneficial, but the age-associated increase becomes detrimental. Inactivating mutations in ANK3/unc-44 reverse this effect and cause detrimental effects in young animals (sensitivity to oxidative stress) and beneficial effect in old animals (increased survival). In humans, we studied if the most significant single nucleotide polymorphism (SNP) for depressive symptoms in ANK3 from our GWAS has a relationship to lifespan, and show a trend towards longer lifespan in individuals with the risk allele for depressive symptoms in men (odds ratio (OR) 1.41, P=0.031) but not in women (OR 1.08, P=0.33). We also examined whether ANK3, by itself or in a panel with other top CFG-prioritized genes, acts as a blood gene-expression biomarker for biological age, in two independent cohorts, one of live psychiatric patients (n=737), and one of suicide completers from the coroner's office (n=45). We show significantly lower levels of ANK3 expression in chronologically younger individuals than in middle age individuals, with a diminution of that effect in suicide completers, who presumably have been exposed to more severe and acute negative mood and stress. Of note, ANK3 was previously reported to be overexpressed in fibroblasts from patients with Hutchinson-Gilford progeria syndrome, a form of accelerated aging. Taken together, these studies uncover ANK3 and other genes in our dataset as biological links between mood, stress and longevity/aging, that may be biomarkers as well as targets for preventive or therapeutic interventions. Drug repurposing bioinformatics analyses identified the relatively innocuous omega-3 fatty acid DHA (docosahexaenoic acid), piracetam, quercetin, vitamin D and resveratrol as potential longevity promoting compounds, along with a series of existing drugs, such as estrogen-like compounds, antidiabetics and sirolimus/rapamycin. Intriguingly, some of our top candidate genes for mood and stress-modulated longevity were changed in expression in opposite direction in previous studies in the Alzheimer disease. Additionally, a whole series of others were changed in expression in opposite direction in our previous studies on suicide, suggesting the possibility of a "life switch" actively controlled by mood and stress.
- Source: Resveratrol Attenuates Trimethylamine-N-Oxide (TMAO)-Induced Atherosclerosis by Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut Microbiota.
- Abstract: The gut microbiota is found to be strongly associated with atherosclerosis (AS). Resveratrol (RSV) is a natural phytoalexin with anti-AS effects; however, its mechanisms of action remain unclear. Therefore, we sought to determine whether the anti-AS effects of RSV were related to changes in the gut microbiota. We found that RSV attenuated trimethylamine-N-oxide (TMAO)-induced AS in ApoE(-/-)mice. Meanwhile, RSV decreased TMAO levels by inhibiting commensal microbial trimethylamine (TMA) production via gut microbiota remodeling in mice. Moreover, RSV increased levels of the genera Lactobacillus and Bifidobacterium, which increased the bile salt hydrolase activity, thereby enhancing bile acid (BA) deconjugation and fecal excretion in C57BL/6J and ApoE(-/-)mice. This was associated with a decrease in ileal BA content, repression of the enterohepatic farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) axis, and increased cholesterol 7a-hydroxylase (CYP7A1) expression and hepatic BA neosynthesis. An FXR antagonist had the same effect on FGF15 and CYP7A1 expression as RSV, while an FXR agonist abolished RSV-induced alterations in FGF15 and CYP7A1 expression. In mice treated with antibiotics, RSV neither decreased TMAO levels nor increased hepatic BA synthesis. Additionally, RSV-induced inhibition of TMAO-caused AS was also markedly abolished by antibiotics. In conclusion, RSV attenuated TMAO-induced AS by decreasing TMAO levels and increasing hepatic BA neosynthesis via gut microbiota remodeling, and the BA neosynthesis was partially mediated through the enterohepatic FXR-FGF15 axis. IMPORTANCE: Recently, trimethylamine-N-oxide (TMAO) has been identified as a novel and independent risk factor for promoting atherosclerosis (AS) partially through inhibiting hepatic bile acid (BA) synthesis. The gut microbiota plays a key role in the pathophysiology of TMAO-induced AS. Resveratrol (RSV) is a natural phytoalexin with prebiotic benefits. A growing body of evidence supports the hypothesis that phenolic phytochemicals with poor bioavailability are possibly acting primarily through remodeling of the gut microbiota. The current study showed that RSV attenuated TMAO-induced AS by decreasing TMAO levels and increasing hepatic BA neosynthesis via gut microbiota remodeling. And RSV-induced hepatic BA neosynthesis was partially mediated through downregulating the enterohepatic farnesoid X receptor-fibroblast growth factor 15 axis. These results offer new insights into the mechanisms responsible for RSV's anti-AS effects and indicate that the gut microbiota may become an interesting target for pharmacological or dietary interventions to decrease the risk of developing cardiovascular diseases.
- Source: Distinct metabolic effects of resveratrol on lipogenesis markers in mice adipose tissue treated with high-polyunsaturated fat and high-protein diets
- Abstract: OBJECTIVE: A healthy diet is essential for the prevention of metabolic syndrome. The present study evaluated the effect of resveratrol associated with high-polyunsaturated fat and high-protein diets on expression of adipogenic and lipogenic genes. RESEARCH METHODS & PROCEDURES: FVB/N mice were divided into 6 groups (n=7 each) and fed with experimental diets for 60days: standard (ST), high-fat diet (HFD), and high-protein diet (HPD), with and without resveratrol (RSV) (4g/kg diet). The body weight, food intake, energy intake (kcal), and blood parameters (HDL-C, total cholesterol, glucose, and triglyceride levels) were assessed. Real-time PCR was performed to analyze the expression of adipogenesis and lipogenesis markers: PPARγ, SREBP-1c, ACC and FAS in samples from perigonadal adipose tissue. RESULTS: In the HPD+RSV group, resveratrol decreased body weight, body adiposity, adipose tissue weight, adipocyte area, total cholesterol, ACC and FAS expression, and increased HDL-cholesterol in comparison to HPD. In the HPD group there was a decrease in adipocyte area, as well as PPARγ, SREBP-1c and ACC expression in comparison to ST. While in HFD+RSV, resveratrol decreased levels of total cholesterol in comparison to HFD. In the HFD group there was decrease in body weight, and PPARγ, SREBP-1c and ACC expression in comparison to ST. CONCLUSIONS: The obtained results show that resveratrol decreases lipogenesis markers and metabolic parameters in the setting of a high-protein diet. Moreover, resveratrol decreased total cholesterol in both diets. These results point to the increased potential of resveratrol use in prevention of metabolic syndrome, acting on different dietary compositions.
- SIRT1 and other sirtuins in metabolism
- Study highlights: Sirtuins respond to energy level changes and execute salutary effects resembling calorie restriction (CR). Sirtuins mediate CR effects in various cellular compartments and are crucial metabolic regulators in multiple tissues. Small molecules that enhance sirtuin activities, including CR mimetics and NAD+ precursors, are promising strategies to ameliorate age-related diseases.
- Abstract: Sirloins such as SIRT1 are conserved protein NAD+-dependent deacylases and thus their function is intrinsically linked to cellular metabolism. Over the past two decades, accumulating evidence has indicated that sirtuins are not only important energy status sensors but also protect cells against metabolic stresses. Sirtuins regulate the aging process and are themselves regulated by diet and environmental stress. The versatile functions of sirtuins including, more specifically, SIRT1 are supported by their diverse cellular location allowing cells to sense changes in energy levels in the nucleus, cytoplasm, and mitochondrion. SIRT1 plays a critical role in metabolic health by deacetylating many target proteins in numerous tissues, including liver, muscle, adipose tissue, heart, and endothelium. This sirtuin also exerts important systemic effects via the hypothalamus. This review will cover these topics and suggest that strategies to maintain sirtuin activity may be on the horizon to forestall diseases of aging.
- Resveratrol, found in grapes, berries and red wine, is one of the most important anti-ageing natural chemicals available, and also possesses lipolytic capacity.
- In a new study published recently it was found that resveratrol boosts mitochondrial activity in brown fat cells under a high fat diet.
- Brown fat cells differ from normal white fat cells in that they burn fat in the mitochondria, thereby reducing obesity and it's effects. This is in contrast to white fat cells, which accumulate fat, leading to obesity.
- Resveratrol was also found to improve insulin sensitivity, a hallmark of diabetes type II.
- This, and many other studies, point to the potential of resveratrol to help reduce body fat accumulation and it's complications.
- Source: The Effects of High Fat Diet and Resveratrol on Mitochondrial Activity of Brown Adipocytes.
- Abstract: BACKGROUND: Resveratrol (RSV) is a polyphenolic phytoalexin that has many effects on metabolic diseases such as diabetes and obesity. Given the importance of brown adipose tissue (BAT) for energy expenditure, we investigated the effects of RSV on brown adipocytes. METHODS: For the in vitro study, interscapular BAT was isolated from 7-week-old male Sprague Dawley rats. For the in vivo study, 7-week-old male Otsuka Long Evans Tokushima Fatty (OLETF) rats were divided into four groups and treated for 27 weeks with: standard diet (SD); SD+RSV (10 mg/kg body weight, daily); high fat diet (HFD); HFD+RSV. RSV was provided via oral gavage once daily during the in vivo experiments. RESULTS: RSV treatment of primary cultured brown preadipocytes promoted mitochondrial activity, along with over-expression of estrogen receptor α (ER-α). In OLETF rats, both HFD and RSV treatment increased the weight of BAT and the differentiation of BAT. However, only RSV increased the mitochondrial activity and ER-α expression of BAT in the HFD-fed group. Finally, RSV improved the insulin sensitivity of OLETF rats by increasing the mitochondrial activity of BAT, despite having no effects on white adipocytes and muscles in either diet group. CONCLUSION: RSV could improve insulin resistance, which might be associated with mitochondrial activity of brown adipocyte. Further studies evaluating the activity of RSV for both the differentiation and mitochondrial activity of BAT could be helpful in investigating the effects of RSV on metabolic parameters.
- Yet another study, published today, which shows that resveratrol boosts fat reduction - and is therefore ideal in the fight against cellulite
- This study shows that resveratrol inhibits the growth of new fat cells (preadipocyte differentiation) and reduces the growth of mitochondria and fat storage in fat cells, leading to weight loss in animals and humans
- Source: Resveratrol inhibits lipogenesis of 3T3-L1 and SGBS cells by inhibition of insulin signalling and mitochondrial mass increase
- Abstract: Resveratrol is attracting much interest because of its potential to decrease body weight and increase life span, influencing liver and muscle function by increasing mitochondrial mass and energy expenditure. Even though resveratrol was already shown to reduce the adipose tissue mass in animal models, its effects on mitochondrial mass and network structure in adipocytes has not yet been studied. For this purpose, we investigated the effect of resveratrol on mitochondrial mass increase and remodelling during adipogenic differentiation of two in vitro models of adipocyte biology, the murine 3 T3-L1 cell line and the human SGBS cell strain. We confirm that resveratrol inhibits lipogenesis in differentiating adipocytes, both mouse and human. We further show that this is linked to inhibition of the normally observed mitochondrial mass increase and mitochondrial remodelling. At the molecular level, the anti-lipogenic effect of resveratrol seems to be mediated by a blunted expression increase and an inhibition of acetyl-CoA carboxylase (ACC). This is one of the consequences of an inhibited insulin-induced signalling via Akt, and maintained signalling via AMP-activated protein kinase. The anti-lipogenic effect of resveratrol is further modulated by expression levels of mitochondrial ATAD3, consistent with the emerging role of this protein as an important regulator of mitochondrial biogenesis and lipogenesis. Our data suggest that resveratrol acts on differentiating preadipocytes by inhibiting insulin signalling, mitochondrial biogenesis, and lipogenesis, and that resveratrol-induced reduction of mitochondrial biogenesis and lipid storage contribute to adipose tissue weight loss in animals and humans.
- Resveratrol is well-known and widely researched for it's anti-ageing, anti-inflammatory and antioxidant action, and for these reasons is an ideal ingredient of anti-ageing, leg wellness and anti-cellulite creams
- Source: Well-Known Antioxidants and Newcomers in Sport Nutrition: Resveratrol
- Abstract: Resveratrol (3,5,4´-trihydroxystilbene) is a natural polyphenolic flavonoid (Baur and Sinclair 2006). It is freely available in food supplements and is found in the seeds and skins of grapes, red wine, mulberries, peanuts and rhubarb (Baur and Sinclair 2006, Nieman et al. 2012). Many in vivo and in vitro studies (Brisdelli et al. 2009, Ventura-Clapier 2012) have provided evidence for neuroprotective, anti-atherogenic, antithrombotic, antihypercholesterolemic, anti-inflammatory, antioxidant, proangiogenic, vasorelaxing and anticancer effects of resveratrol. Interestingly, it has also been shown that resveratrol increases skeletal muscle mitochondrial biogenesis and fatty acid oxidation in many tissues as well as exercise performance in mice (Dolinsky et al. 2012). Pharmacokinetic studies indicate that resveratrol has a poor bioavailability. Resveratrol, even at the high dosage of 750 mg (kg·body weight–1) per day for 13 weeks by the oral route, has been shown to have no adverse effects (Edwards et al. 2011). Pharmacological studies also suggest that therapeutic doses of resveratrol are non-toxic, easily absorbed and well tolerated by humans. A dose of 150 mg·kg–1·day–1 has been used in the study of Dolinsky et al. (2012), while other studies have shown that lower doses of 20 mg.kg–1.day–1 proved to be efficient in preventing cardiac dysfunction (Rimbaud et al. 2011) and pulmonary hypertension (Csiszar et al. 2009) and also in vasoprotection (Ungvari et al. 2007). Interest in resveratrol in sport medicine arose after animal studies assessed endurance performance of mice and found a dose-dependent increase in exercise tolerance, improved motor skills and increased number and activity of mitochondria in muscle cells. Both exercise and resveratrol are thought to trigger biochemical cascades, leading to improved mitochondrial function and energy metabolism. Indeed, it has been shown that resveratrol enhances mitochondrial biogenesis and induces adenosine 5´ monophosphate-activated protein kinase (AMPK) in the skeletal muscle of mice (Baur and Sinclair 2006, Lagouge et al. 2006). However, when SIRT1 was knocked out, these effects were absent (Price et al. 2012). Resveratrol as a food supplement in sport medicine has not received much attention especially in human studies, despite some basic scientific evidence that this substance could have multiple indications related to high-performance sport (Nieman et al. 2012). Resveratrol has been also touted as an exercise mimetic effect through its activation of SIRT1 and AMPK (Hart et al. 2013). To support this hypothesis, it has been demonstrated that resveratrol supplementation increases the exercise performance in aged mice (Murase et al. 2009) and mice fed by a Western diet (Lagouge et al. 2006) in the absence of exercise training, suggesting that resveratrol can stimulate pathways similar to exercise. Ryan et al. (2010)demonstrated that 10 days of resveratrol supplementation also diminishes the basal levels of oxidative stress associated with ageing. Functional measurements of maximal isometric force and rate of fatigue were unaffected by resveratrol supplementation in aged animals. Mice treated with resveratrol demonstrated elevations in AMPK activation and PGC-1α expression, along with increases in mitochondria in animals fed by a high fat diet (Baur and Sinclair 2006). Additionally, enhanced SIRT1 activity like exercise training decreases plasma glucose levels, improves insulin sensitivity, increases mitochondrial number and function, decreases adiposity, improves exercise tolerance and potentially lowers body weight (Elliott and Jirousek 2008). The induction of PGC-1α and activation of AMPK are commonly observed following both exercise and resveratrol administration (Ruderman and Prentki 2004,Baur and Sinclair 2006, Lagouge et al. 2006, Zang et al. 2006). Menzies et al. (2013) demonstrated that SIRT1 protein is responsible for the partial maintenance of basal mitochondrial content and function, in addition to lowering mitochondrial ROS generation and improving fatigue in skeletal muscle. They also showed that resveratrol can activate both AMPK and p38 in temporally distinct stages, which could promote post-translational changes in PGC-1α, thereby altering its activity (Jäger and Nguyen-Duong 1999). These studies (Jäger and Nguyen-Duong 2007, Menzies et al. 2013) also demonstrated that high doses of resveratrol were necessary for AMPK-mediated activation of SIRT1. The resveratrol-induced improvement in energy metabolism is at least partly mediated by specific signal transduction pathways and resveratrol seems mediated by enhanced mitochondrial biogenesis with the activation of the AMPK-SIRT1-PGC-1α pathway (Ventura-Clapier 2012). Resveratrol administration seems to induce a higher aerobic capacity in mice, as shown by the increased running time and oxygen consumption in muscle fibres (Menzies et al. 2013). Similarly, Hart et al. (2013) suggested that resveratrol supplementation enhanced the effects of exercise on endurance capacity, and this was shown in rats which already had a high level of aerobic endurance. These findings suggest that resveratrol could be used as a performance enhancer (Baur and Sinclair 2006, Lagouge et al. 2006). Dolinsky et al. (2012) demonstrated that a combination of resveratrol and exercise training increased time to exhaustion compared to exercise training. The authors suggested that resveratrol optimises fatty acid metabolism, which may contribute to the increased contractile force response of skeletal muscles.
- Source: Pterostilbene surpassed resveratrol for anti-inflammatory application: Potency consideration and pharmacokinetics perspective
- Abstract: This study aimed to evaluate the suitability of pterostilbene for anti-inflammatory application. The in vitro anti-inflammatory activities of pterostilbene were assessed using resveratrol, piceatannol and resveratrol trimethyl ether as comparators while its pharmacokinetics was examined in rats. All tested compounds displayed concentration-dependent anti-proliferative effect in E11 human rheumatoid arthritic synovial fibroblasts. They also suppressed LPS-induced NF-κB p65 nuclear translocation, down-regulated the secretions of IL-6, IL-18, VEGF, nitric oxide, MMP-2 and MMP-9 in E11 cells and attenuated E11-driven migration of THP-1 and U937 monocytes. Similarly, they inhibited LPS-induced pro-inflammatory cytokines in THP-1 cells. Interestingly, pterostilbene usually displayed in vitro anti-inflammatory potencies stronger than resveratrol.In vivo studies revealed that pterostilbene was extensively distributed to major drug target organs like liver, kidney, heart, lung as well as brain and repeated oral dosing did not significantly alter its pharmacokinetics. In conclusion, pterostilbene appears to be a promising candidate for further development.
- The natural anti-aging chemical resveratrol was shown in this study to inhibit the growth of new fat tissue - and consequently the growth of cellulite - by activating a protein called Wnt/β-catenin. Pterostilbene, which also activates SIRT1 and is more bioavailable should exert the same effect.
- In combination with other anti-cellulite actives, resveratrol and pterostilbene can be a valuable component of anti-cellulite creams
- On the other hand, nicotinamide / vitamin B3, which is erroneously used in anti-cellulite creams, was shown in the same study to actually stimulate the growth of fat tissue
- Technical summary: Resveratrol, via SIRT1 activation, inhibits adipogenesis by regulating Wnt/β-catenin signalling
- Source: SIRT1 inhibits adipogenesis and promotes myogenic differentiation in C3H10T1/2 pluripotent cells by regulating Wnt signaling
- Abstract: BACKGROUND: The directed differentiation of mesenchymal stem cells (MSCs) is tightly controlled by a complex network. Wnt signaling pathways have an important function in controlling the fate of MSCs. However, the mechanism through which Wnt/β-catenin signaling is regulated in differentiation of MSCs remains unknown. SIRT1 plays an important role in the regulation of MSCs differentiation. RESULTS: This study aimed to determine the effect of sirtuin 1 (SIRT1) on adipogenesis and myogenic differentiation of C3H10T1/2 cells. First, the MSC commitment and differentiation model was established by using 5-azacytidine. Using the established model, C3H10T1/2 cells were treated with SIRT1 activator/inhibitor during differentiation. The results showed that resveratrol inhibits adipogenic differentiation and improves myogenic differentiation, whereas nicotinamide promotes adipogenic differentiation. Notably, during commitment, resveratrol blocked adipocyte formation and promoted myotubes differentiation, whereas nicotinamide enhanced adipogenic potential of C3H10T1/2 cells. Furthermore, resveratrol elevated the expression of Cyclin D1 and β-catenin in the early stages. The luciferase assay showed that knockdown SIRT1 inhibits Wnt/β-catenin signaling, while resveratrol treatment or overexpression SIRT1 activates Wnt/β-catenin signaling. SIRT1 suppressed the expression of Wnt signaling antagonists sFRP2 and DACT1. Knockdown SIRT1 promoted adipogenic potential of C3H10T1/2 cells, whereas overexpression SIRT1 inhibited adipogenic differentiation and promoted myogenic differentiation. CONCLUSIONS: Together, our results suggested that SIRT1 inhibits adipogenesis and stimulates myogenic differentiation by activating Wnt signaling.
- SIRT1 activation can inhibit NF-κB, and thereby inflammation, in adipose tissue, via multiple pathways.
- Low grade inflammation is a major component of the metabolic syndrome, diabetes, and of course cellulite.
- Pterostilbene and resveratrol activate SIRT1 expression in adipose tissue, which in turn inhibits inflammation, and thereby can help treat cellulite, via either oral or local application, as components of a cellulite cream.
- Source: Molecular Mechanisms of Latent Inflammation in Metabolic Syndrome. Possible Role of Sirtuins and Peroxisome Proliferator-Activated Receptor Type γ.
- Abstract: The problem of metabolic syndrome is one of the most important in medicine today. The main hazard of metabolic syndrome is development of latent inflammation in adipose tissue, which promotes atherosclerosis, non-alcoholic fatty liver disease, myocarditis, and a number of other illnesses. Therefore, understanding of molecular mechanisms of latent inflammation in adipose tissue is very important for treatment of metabolic syndrome. Three main components that arise during hypertrophy and hyperplasia of adipocytes underlie such inflammation: endoplasmic reticulum stress, oxidative stress, and hypoxia. Each of these components mediates activation in different ways of the key factor of inflammation - NF-κB. For metabolic syndrome therapy, it is suggested to influence a number of inflammatory signaling components by activating other cell factors to suppress development of inflammation. Such potential factors are peroxisome proliferator-activated receptors type γ that suppress transcription factor NF-κB through direct contact or via kinase of a NF-κB inhibitor (IKK), and also the antiinflammatory transcription factor AP-1. Other possible targets are type 3 NAD+-dependent histone deacetylases (sirtuins). There are mutually antagonistic relationships between NF-κB and sirtuin type 1 that prevent development of inflammation in metabolic syndrome. Moreover, sirtuin type 1 inhibits the antiinflammatory transcription factor AP-1. Study of the influence of these factors on the relationship between macrophages and adipocytes, macrophages, and adipose tissue-derived stromal cells can help to understand mechanisms of signaling and development of latent inflammation in metabolic syndrome.