Pterostilbene, leg wellness & cellulite
PTEROSTILBENE, A BOTANICAL EXTRACT FOUND IN berries, BLACK GRAPES & RED WINE
Pterostilbene (dimethoxy-resveratrol), found in black/purple grapes, blueberries and several other plants is one of the most well-known anti-ageing actives known today, and shares similar properties to it's chemical analog, resveratrol (also found in purple/black grapes and red wine). Both have been found in numerous studies to be powerful antioxidant, anti-inflammatory and lipolytic actives and to reduce excessive skin pigmentation, but above all they are known for their anti-ageing action, based on sirtuin (SIRT1) enhancement. Furthermore, pterostilbene is much more bioavailable than resveratrol, making it more effective than it's famous chemical cousin. For all those reasons, pterostilbene is of great importance as active ingredient in anti-ageing, anti-cellulite, leg wellness, skin brightening and under-eye creams.
Discover the Celluence® creams
Concentrated anti-cellulite / leg wellness formulations
Celluence® Phase One / Phase Two
Concentrated leg wellness / cellulite creams, each featuring 20x different active ingredients, for maximum synergy
Tracked worldwide delivery
UK: £4.50 | EU: £12.50 | US, OZ, CA: FREE
ALL PAPERS AND ARTICLES
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
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.
- Source: Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer's disease.
- Abstract: Recent studies have implicated resveratrol and pterostilbene, a resveratrol derivative, in the protection against age-related diseases including Alzheimer's disease (AD). However, the mechanism for the favorable effects of resveratrol in the brain remains unclear and information about direct cross-comparisons between these analogs is rare. As such, the purpose of this study was to compare the effectiveness of diet-achievable supplementation of resveratrol to that of pterostilbene at improving functional deficits and AD pathology in the SAMP8 mouse, a model of accelerated aging that is increasingly being validated as a model of sporadic and age-related AD. Furthermore we sought to determine the mechanism of action responsible for functional improvements observed by studying cellular stress, inflammation, and pathology markers known to be altered in AD. Two months of pterostilbene diet but not resveratrol significantly improved radial arm water maze function in SAMP8 compared with control-fed animals. Neither resveratrol nor Pterostilbene increased sirtuin 1 (SIRT1) expression or downstream markers of sirtuin 1 activation. Importantly, markers of cellular stress, inflammation, and AD pathology were positively modulated by pterostilbene but not resveratrol and were associated with upregulation of peroxisome proliferator-activated receptor (PPAR) alpha expression. Taken together our findings indicate that at equivalent and diet-achievable doses pterostilbene is a more potent modulator of cognition and cellular stress than resveratrol, likely driven by increased peroxisome proliferator-activated receptor alpha expression and increased lipophilicity due to substitution of hydroxy with methoxy group in pterostilbene.
- 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: Pterostilbene-induced changes in gut microbiota composition in relation to obesity.
- Abstract: SCOPE: Nutritional interventions based on the use of natural bioactive compounds might offer new possibilities for reshaping obesity-associated bacterial dysregulation or dysbiosis and improving health. We evaluated whether pterostilbene supplementation could induce changes in gut microbiota (GM) composition and whether these modifications were associated with improvements in metabolic variables. METHODS AND RESULTS: Zucker (fa/fa) rats were given a standard diet supplemented (n = 10) or not (n = 9) with pterostilbene (15 mg/kg body weight/day) by oral gavage for 6 weeks. Faecal samples at the beginning and at the end of the intervention period were analysed by Illumina Mi-Seq sequencing approach. Pterostilbene exerted protective anti-obesity effects, improved metabolic function (insulin sensitivity) and induced structural changes in GM composition. A decrease in the levels of Firmicutes and an increase in Verrucomicrobia phyla were detected in the pterostilbene-treated group. Bacterial species belonging to genera Akkermansia and Odoribacter were also increased. A strong inverse correlation between Akkermansia muciniphila and body-weight was evidenced. Odoribacter splanchnicus showed a negative correlation with adiposity. CONCLUSION: Pterostilbene modifies intestinal bacteria composition towards a healthier microbial profile and suggests that the anti-obesity effects induced in Zucker rats could be associated with an enrichment of the mucin-degrading bacterial members, namely Akkermansia and Odoribacter genus.
- 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.
- Source: Topical treatment with pterostilbene, a natural phytoalexin, effectively protects hairless mice against UVB radiation-induced skin damage and carcinogenesis,
- Abstract: The aim of our study was to investigate in the SKH-1 hairless mouse model the effect of pterostilbene (Pter), a natural dimethoxy analog of resveratrol (Resv), against procarcinogenic ultraviolet B radiation (UVB)-induced skin damage. Pter prevented acute UVB (360 mJ/cm(2))-induced increase in skin fold, thickness, and redness, as well as photoaging-associated skin wrinkling and hyperplasia. Pter, but not Resv, effectively prevented chronic UVB (180 mJ/cm(2), three doses/week for 6 months)-induced skin carcinogenesis (90% of Pter-treated mice did not develop skin carcinomas, whereas a large number of tumors were observed in all controls). This anticarcinogenic effect was associated with (a) maintenance of skin antioxidant defenses (i.e., glutathione (GSH) levels, catalase, superoxide, and GSH peroxidase activities) close to control values (untreated mice) and (b) an inhibition of UVB-induced oxidative damage (using as biomarkers 8-hydroxy-2'-deoxyguanosine, protein carbonyls, and isoprostanes). The molecular mechanism underlying the photoprotective effect elicited by Pter was further evaluated using HaCaT immortalized human keratinocytes and was shown to involve potential modulation of the Nrf2-dependent antioxidant response.
- Source: The berry constituents quercetin, kaempferol, and pterostilbene synergistically attenuate reactive oxygen species: involvement of the Nrf2-ARE singling pathway,
- Abstract: Quercetin, kaempferol, and pterostilbene are abundant in berries. The anti-oxidative properties of these constituents may contribute to cancer chemoprevention. However, their precise mechanisms of action and their combinatorial effects are not completely understood. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulates anti-oxidative stress enzymes and Phase II drug metabolizing/detoxifying enzymes by binding to antioxidant response element (ARE). This study aimed to investigate the anti-oxidative stress activities of quercetin, kaempferol, and pterostilbene individually and in combination, as well as the involvement of the Nrf2-ARE signaling pathway. Quercetin, kaempferol, and pterostilbene all exhibited strong free-radical scavenging activity in the DPPH assay. The MTS assay revealed that low concentration combinations we tested were relatively non-toxic to HepG2-C8 cells. The results of the DCFH-DA assay and combination index (CI) indicated that quercetin, kaempferol, and pterostilbene attenuated intracellular reactive oxygen species (ROS) levels when pretreated individually and had synergistic effects when used in combination. In addition, the combination treatment significantly induced ARE and increased the mRNA and protein expression of Nrf2-regulated genes. Collectively, our study demonstrated that the berry constituents quercetin, kaempferol, and pterostilbene activated the Nrf2-ARE signaling pathway and exhibited synergistic anti-oxidative stress activity at appropriate concentrations.
- Pterostilbene inhibits lipid accumulation through cell cycle delay in 3T3-L1 adipocyte
- Obesity is caused abnormal or excessive fat accumulation that presents a risk to health such as high blood pressure, type 2 diabetes and atherosclerosis. However, recent studies have reported that resveratrol has numerous beneficial effect on cardio-protective, anti-cancer and obesity. Pterostilbene is a stilbenoid and structurally related to resveratrol. Pterostilbene have reported that anti-oxidant, anti-inflammatory, and anti-carcinogenic properties more than resveratrol. Objective: In this study, we examined that pterostilbene inhibits lipid accumulation by cell cycle delay. ABSTRACT: Methods: We investigated Cell viability of pterostilbene through XTT assay. Lipid accumulation of 3T3-L1 checked by using Oil-Red O staining. We experimented western blot to check down regulating obesity-related genes in protein level. Results: Pterostilbene delayed cell cycle in the S phage which is related with delay of cell differentiation. Pterostilbene decreased the accumulation of lipid droplets. The expression of Peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT-enhancer-binding proteins (C/EBPα), and adipocyte protein 2 was decreased by pterostilbene. In addition, pterostilbene reduced lipogenesis (LPAATθ, lipin1, and DGAT1) and fatty acid synthesis (FASN, SREBP) factor in protein level dose dependent manner. Conclusion: Our findings show that pterostilbene inhibits lipid accumulation by regulating adipogenic factors and delaying cell cycle.
- 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.
- Source: Well-Known Antioxidants and Newcomers in Sport Nutrition: Coenzyme Q10, Quercetin, Resveratrol, Pterostilbene, Pycnogenol and Astaxanthin
- Abstract: Physical exercise induces an increase in production of free radicals and other reactive oxygen species (ROS) (Davies et al. 1982, Borzone et al. 1994, Halliwell and Gutteridge 1999). Current evidence indicates that ROS are the primary reason of exercise-induced disturbances in muscle redox balance. Severe disturbances in redox balance have been shown to promote oxidative injury and muscle fatigue (Reid et al. 1992, O’Neill et al. 1996) and thus impair the exercise performance. There are several potential sources of ROS that can be activated by exercise such as mitochondrial electron transfer chain, in the purine degradation pathway the reaction catalysed by xanthine oxidase, macrophage infiltration and metabolic degradation of catecholamines (Urso and Clarkson 2003, Finaud et al. 2006). The high production of ROS during exercise is also responsible for muscular damage (Aguiló et al. 2007). On the basis of the above-mentioned information, sportsmen have to improve their antioxidant defence systems to overcome the exercise-induced oxidative damage. Over the past few decades, many attempts have been made to improve antioxidant potential and therefore increase physical performance by improving nutrition, training programmes and other related factors. An antioxidant is generally defined as any substance that significantly delays or prevents oxidative damage of a target molecule (Halliwell 2007). The antioxidant defence system of the body consists of antioxidant enzymes (superoxide dismutases, catalase and glutathione peroxidase, etc.) and non-enzymatic antioxidants (vitamins A, C and E, coenzyme Q10 (CoQ10) and glutathione, etc.) (Deaton and Marlin 2003). There is a cooperative interaction between endogenous antioxidants and dietary antioxidants; therefore, antioxidant supplementation may improve the muscle fibre’s ability to scavenge ROS and protect the exercising muscle against exercise-induced oxidative damage and fatigue. However, antioxidant nutrient deficiency could induce an increased susceptibility to exercise-induced damage and thus leads to impaired exercise performance (Stear et al. 2009). Recently, the problem of whether or not athletes should use antioxidant supplements is an important and highly debated topic. To prevent these hypothetically negative or side effects of physical exercise, supplementation with different types of antioxidants has been used in a great number of studies (Snider et al. 1992, Rokitzki et al. 1994, Reid et al. 1994, Margaritis et al. 1997, Aguiló et al. 2007, Bloomer et al. 2012). In the context of this chapter, information in brief about the well-known and recently used antioxidants such as CoQ10, quercetin, resveratrol, pterostilbene, pycnogenol and astaxanthine is given. The effects of these antioxidants on exercise performance and exercise-induced oxidative stress are also explained. Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene) is a stilbenoid chemically similar to resveratrol and is found in grapes, wine and berries (Rimando et al. 2004). Pterostilbene is generated by plants in response to microbial infestation or exposure to ultraviolet light (Langcake 1981). Pterostilbene is closely related structurally to resveratrol (a naturally occurring dimethylether analogue of resveratrol) and shows many of the same characteristics, as well as its own unique therapeutic potential (Rimando et al. 2002). Pterostilbene might show higher biological activity compared with resveratrol, because substitution of a hydroxy with a methoxy group increases the transport into cells and increases the metabolic stability of the molecule. Therefore, pterostilbene is not as quickly glucuronidated and sulphated as resveratrol. Pterostilbene is known to have many pharmacological benefits for the prevention and treatment of a wide variety of diseases, including cancer (McCormack and McFadden 2012), dyslipidaemia (Rimando et al. 2005), diabetes (Amarnath Satheesh and Pari 2006), cardiovascular degeneration (Amarnath Satheesh and Pari 2008) and pain (Hougee et al. 2005). Antioxidant and antiinflamatory effects of pterostilbene are also demonstrated (Roupe et al. 2006, Perečko et al. 2010, Hsu et al. 2013). Pterostilbene possesses strong, dose-dependent antioxidant effects (Rimando et al. 2002, Amorati et al. 2004). The antioxidant activity of pterostilbene was first demonstrated in vitro by its inhibition of methyl linoleate oxidation (Roupe et al. 2006). It inhibits the production of hydroxyl radicals (Perečko et al. 2010). In terms of the antiinflamatory effect of pterostilbene, Hsu et al. (2013) demonstrated that pterostilbene downregulates inflammatory TNF-α, IL-6, cyclooxygenase-2, inducible nitric oxide synthase, IL-1β, monocyte chemotactic protein-1, C-reactive protein and plasminogen activator inhibitor-1 expression by inhibiting the activation of NF-κB. According to our knowledge, to date no study has investigated the effects of pterostilbene supplementation on exercise performance, exercise-induced oxidative stress and inflammatory response in both sedentary and trained individuals. On the basis of the current studies, pterostilbene may improve athletic performance by activating and supporting both antioxidant and antiinflamatory cascades in untrained and trained subjects. However, detailed animal and human studies are needed in this subject.
- 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.
- Pterostilbene, a dimethyl ether derivative of resveratrol, reduces fat accumulation in rats fed an obesogenic diet
- The current study aimed to demonstrate the effects of pterostilbene in rats fed an obesogenic diet. For this purpose, pterostilbene was administered at doses of 15 mg/kg body weight/day (PT15 group) or 30 mg/kg body weight/day (PT30 group) for 6 weeks. Pterostilbenereduced adipose tissue mass -15.1% (PT15) and -22.9% (PT30). In this tissue, it decreased malic enzyme (-39.4 and -49.5% for PT15 and PT30 groups, respectively) and fatty acid synthase (-45 and -53.4% for PT15 and PT30) activities. Acetyl-CoA carboxylase activity was reduced and AMPK activity was increased only in the PT30 group. In the liver, pterostilbene (PT30) reduced malic enzyme (-29.5%) and glucose-6-P dehydrogenase (-43.2%) activities and increased carnitine palmitoyltransferase-1a (37.5%) and acyl-coenzyme A oxidase (42.5%) activities. This increased oxidative capacity was not associated with increased mitochondriogenesis. Among biochemical serum parameters, only insulin was modified by pterostilbene (-31.6%) in the PT15 group. The amounts of pterostilbene in serum and tissues from rats in the PT30 group were in all cases 2-fold greater than those found in the PT15 group. In conclusion, pterostilbene shows antiobesity properties due, at least in part, to reduced lipogenesis in adipose tissue and increased fatty acid oxidation in liver.
- 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.
- Polyphenols comprise a large class of plant/fruit-derived molecules with multiple benefits for human health. Resveratrol has been extensively studied for its anti-diabetic, neuroprotective, skimming, heart-protective and anti-cancer properties.
- However its low bioavailability strongly limits it's potential. On the other hand, resveratrol's sister compound, pterostilbene, has shown similar or even more potent antitumor activities than resveratrol, due to pterostilbene's 7.5 times higher bioavailability.
- In this study on mice, pterostilbene was found to "induce tumor cell cycle arrest and autophagy activation at bioavailable concentrations", i.e. on concentrations achievable by oral or intervenors administration.
- On the other hand, resveratrol could not induce cancer cell death at biologically achievable concentrations.
- Source: Pterostilbene, a natural polyphenol with anticancer activity, induces tumor cell death through autophagy activation
- Abstract: Polyphenols (PFs) conform a large class of plants/fruits-derived molecules with potential benefits for human health. Resveratrol (Resv) (3,4′,5-trihydroxy-trans-stilbene), has been extensively studied for its anti-diabetic, neuroprotective, anti-adipogenic, cardioprotective and anti-tumoral properties. However its low bioavailability (half-life in blood was 10.2 minutes after i.v. adm. of 20 mg/kg to mice) strongly limits Resv potential in vivo. Thus, compounds that may mimic Resv effects, but showing more bioavailability, may improve health benefits and should be investigated. Pterostilbene (Pter) (3,5-dimethoxy-4′-hydroxystilbene, another natural phytoalexin), has shown similar or even more potent antitumor activities than Resv. However, Pter's half-life in mouse blood (77.9 min) is approx. 7.5 times higher. Pter causes cancer cell death in vitro at bioavailable concentrations, and decreases tumor growth in mice. The aim of our present study was a) to determine whether Pter causes cytotoxicity in human tumors at concentrations that are reliable under in vivo conditions; and b) identify which death-related molecular mechanisms are activated by Pter. For these purposes we used a panel of different human tumors: melanoma, breast cancer, lung cancer, and colon cancer. Resv and Pter were assayed in a μM range, between 10 μM (below the IC50 for all cell lines) and 200 μM (an unachievable in vivo concentration). Cell cycle and death induction were determined by flow cytometry. The effects observed in the presence of Resv or Pter, under in vitro conditions, were concentration and exposure time dependent. In fact, an increase in PF concentration switched the type tumor cell death. Resv or Pter induced inhibition of tumor cell division and autophagy activation, although no caspase 3 activation was detected within a 24 h-period in the presence of either PF. On the other hand by further increasing Resv or Pter concentration, apoptosis and necrosis were progressively activated as shown by flow cytometry, caspase 3 activity and lactate dehydrogenase activity released to the culture medium. The main difference between Resv and Pter is the effective concentration, much lower for Pter and thus close to bioavailable levels. Whereas bioavailable levels of Resv do not cause tumor cell death. Different molecular events associated Pter with autophagy activation: a) an increase of LC3-II form, indicating the processing of LC3 protein to its lipidated form; b) an increase in P62 bands and GFP-LC3 punctation were observed thus indicating P62 accumulation and translocation of LC3 to autophagic membranes, respectively. Besides low levels of Pter, in addition of activating autophagy, also cause a rapid loss of tubulin organization as detected by immunochemistry. Therefore our results demonstrate that Pter induces tumor cell cycle arrest and autophagy activation at bioavailable concentrations.