Endothelium-dependent vasodilator and antioxidant properties of a novel enzymatic extract of grape pomace from wine industrial waste

The aim of the present study was to evaluate the vascular effects of an enzymatic extract of grape pomace (GP-EE) on isolated arteries, focusing our attention on endothelium-derived relaxation and on its antioxidant properties. Grape pomace derived from wine making was extracted by an enzymatic process and its composition of polyphenols was evaluated by HPLC and ESI-MS/MS, detecting kaempferol, catechin, quercetin and procyanidins B1 and B2, trace levels of resveratrol and tracing out gallocatechin and anthocyanidins. GP-EE induced endothelium- and NO-dependent vasodilatation of both rat aorta and small mesenteric artery (SMA) segments and reduced Phe-induced response in aortic rings. Both ORAC and DPPH assays confirmed antioxidant scavenging properties of GP-EE, which also prevented O(2)(·-) production (assessed by DHE fluorescence) and contraction elicited by ET-1. These results provide evidence that GP-EE possesses interesting antioxidant and protective vascular properties and highlight the potential interest of this extract as a functional food.     

Resveratrol as an anti-inflammatory and anti-aging agent: mechanisms and clinical implications

Resveratrol is a phytoalexin polyphenolic compound found in various plants, including grapes, berries, and peanuts. Multiple lines of compelling evidence indicate its beneficial effects on neurological, hepatic, and cardiovascular systems. Also one of the most striking biological activities of resveratrol soundly investigated during the late years has been its cancer-chemopreventive potential. In fact, recently it has been demonstrated that this stilbene blocks the multistep process of carcinogenesis at various stages: tumor initiation, promotion, and progression. One of the possible mechanisms for its biological activities involves downregulation of the inflammatory response through inhibition of synthesis and release of pro-inflammatory mediators, modification of eicosanoid synthesis, inhibition of activated immune cells, or inhibiting such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) via its inhibitory effects on nuclear factor (kappa)B (NF-(kappa)B) or the activator protein-1 (AP-1). More recent data provide interesting insights into the effect of this compound on the lifespan of yeast and flies, implicating the potential of resveratrol as an anti-aging agent in treating age-related human diseases. It is worthy to note that the phenolic compound possesses a low bioavailability and rapid clearance from the plasma. As the positive effects of resveratrol on inflammatory response regulation may comprise relevant clinical implications, the purpose of this article is to review its strong anti-inflammatory activity and the plausible mechanisms of these effects. Also, this review is intended to provide the reader an up-date of the bioavailability and pharmacokinetics of resveratrol and its impact on lifespan.     

Epigenetic effects of natural polyphenols: A focus on SIRT1‐mediated mechanisms

Polyphenols are a class of natural compounds widely distributed in fruits, vegetables, and plants. They have been reported to possess a wide range of activities in prevention and alleviation of various diseases like cancer, neuroinflammation, diabetes, and aging. Polyphenols are effective against chronic diseases and recent reports indicated strong epigenetic effects of polyphenols. Most of the studies investigating epigenetic effects of natural polyphenols have focused on their beneficial effects in cancer treatment. However, epigenetic defects have been demonstrated in many other diseases as well, and application of polyphenols to modulate the epigenome is becoming an interesting field of research. This review summarizes the effects of natural polyphenols in modulating epigenetic‐related enzymes as well as their effect in prevention and treatment of chronic diseases with a focus on SIRT1 modulation. We have also discussed the relation between the structure and function of epigenetic‐modifying polyphenols.     

Regulation of the intestinal tight junction by natural polyphenols: A mechanistic perspective

Impairment of the epithelial barrier function is closely linked to the pathogenesis of various gastrointestinal diseases, food allergies, type I diabetes, and other systematic diseases. Plant-derived polyphenols are natural secondary metabolites and exert various physiological benefits, including anti-inflammatory, anti-oxidative, anti-carcinogenic, and anti-aging effects. Recent studies also show the role of plant polyphenols in regulation of the intestinal barrier and prevention of intestinal inflammatory diseases. Here we summarize the regulatory pathways and mediators linking polyphenols to their beneficial effects on tight junction and gut epithelial barrier functions, and provide useful information about using polyphenols as nutraceuticals for intestinal diseases.     

Resveratrol and health--a comprehensive review of human clinical trials

In the past decade, the small polyphenol resveratrol has received widespread attention as either a potential therapy or as a preventive agent for numerous diseases. Studies using purified enzymes, cultured cells, and laboratory animals have suggested that resveratrol has anti-aging, anti-carcinogenic, anti-inflammatory, and anti-oxidant properties that might be relevant to chronic diseases and/or longevity in humans. Although the supporting research in laboratory models is quite substantial, only recently data has emerged to describe the effects of resveratrol supplementation on physiological responses in humans. The limited number of human clinical trials that are available has largely described various aspects of resveratrol's safety and bioavailability, reaching a consensus that it is generally well-tolerated, but have poor bioavailability. Very few published human studies have explored the ability of resveratrol to achieve the physiological benefits that have been observed in laboratory models, although many clinical trials have recently been initiated. This review aims to examine the current state of knowledge on the effects of resveratrol on humans and to utilize this information to develop further guidelines for the implementation of human clinical trials.     

Resveratrol,human health and winemaking perspectives

Resveratrol, (3, 5, 4′-trihydroxystilbene) is a non-flavonoid polyphenol stilbene synthesized by plants when damaged by infectious diseases or ionizing radiation. Although present in more than seventy plant species, grapes and wine are the major dietary contributors of resveratrol, responsible for 98% of the daily intake. In 1992, Renaud and De Lorgeril first linked wine polyphenols, including resveratrol, to the potential health benefits ascribed to regular and moderate wine consumption (the so called “French Paradox”). Since then, resveratrol has received increasing scientific interest, leading to research on its biological actions, and to a large number of published papers, which have been collected and discussed in this review. The relatively low amounts of resveratrol measured in wine following moderate consumption, however, may be insufficient to mitigate biological damage, such as that due to oxidative stress. On this basis, the authors also highlight the importance of viticulture and the winemaking process to enhance resveratrol concentrations in wine in order to bolster potential health benefits.     

Antioxidant Activity and Protective Effect on DNA Cleavage of Resveratrol

ABSTRACT: The major natural polyphenols of wine are flavonoids. Red wine also contains a natural phytoalexin called resveratrol which recently has been the subject of conflicting reports regarding its protective role against cardiovascular diseases. We have investigated the free radical scavenging capacity of resveratrol, its effects on xanthine oxidase (XO) activity, spontaneous membrane lipid oxidation, and DNA cleavage. Resveratrol showed a dose-dependent free radical scavenging activity, significant inhibition of XO activity, an anti-lipoperoxidative capacity, and a protective effect on DNA cleavage. The antioxidant capacity of resveratrol is ascribed to the concomitant activities of scavenging free radicals, metal chelating, and inhibition of some enzymes involved in free radical generation.     

葡萄酒中的多酚类物质及其保健功能

流行病学研究表明 ,适量的饮用葡萄酒有益于身体健康。进一步的研究表明 ,葡萄酒中含有较高水平的多酚类物质 ,如白藜芦醇 ,槲皮酮和儿茶酚等 ,这些物质是强抗氧化剂 ,具有抑制冠心病、动脉粥样硬化、消除自由基、抗癌和抗炎症等作用。文中介绍了葡萄酒中的多酚类物质 ,以及它们的生物活性和作用机理。     

Potential oral health benefits of cranberry

In the past decade, cranberry extracts have been attracting ever-growing attention by dental researchers. The potential benefits of cranberry components in reducing oral diseases, including dental caries and periodontitis, are discussed in this review. A non-dialysable cranberry fraction enriched in high molecular weight polyphenols has very promising properties with respect to cariogenic and periodontopathogenic bacteria, as well as to the host inflammatory response and enzymes that degrade the extracellular matrix. Cranberry components are potential anti-caries agents since they inhibit acid production, attachment, and biofilm formation by Streptococcus mutans. Glucan-binding proteins, extracellular enzymes, carbohydrate production, and bacterial hydrophobicity, are all affected by cranberry components. Regarding periodontal diseases, the same cranberry fraction inhibits host inflammatory responses, production, and activity of enzymes that cause the destruction of the extracellular matrix, biofilm formation, and adherence of Porphyromonas gingivalis, and proteolytic activities and coaggregation of periodontopathogens. The above-listed effects suggest that cranberry components, especially those with high molecular weight, could serve as bioactive molecules for the prevention and/or treatment of oral diseases.     

Dietary polyphenols and type 2 diabetes: Human Study and Clinical Trial

Abstract

Significant evidence from epidemiological investigations showed that dietary polyphenols might manage and prevent type 2 diabetes (T2D). This review summarizes human studies and clinical trials of polyphenols as anti-diabetic agents. Polyphenols from coffee, guava tea, whortleberry, olive oil, propolis, chocolate, red wine, grape seed, and cocoa have been reported to show anti-diabetic effects in T2D patients through increasing glucose metabolism, improving vascular function as well as reducing insulin resistance and HbA1c level. However, individual flavonoid or isoflavonoid compounds appear to have no therapeutic effect on diabetes, based on the limited clinical data. Preliminary clinical trials provided evidence that resveratrol had anti-diabetic activity in humans by improving glycemic control in subjects with insulin resistance. Besides, anthocyanins exhibited anti-diabetic properties by reducing blood glucose and HbA1c levels or the improvement of insulin secretion and resistance. The structure-activity relationship of polyphenols as anti-diabetic agents in humans has been rarely reported.     

多酚类化合物基于非编码RNA调控发挥抗肿瘤及辐射增敏作用研究进展

恶性肿瘤严重危害人类生命健康，放疗是目前治疗恶性肿瘤常用的方法之一。然而电离辐射会引起肿瘤细胞的辐射抗性并损伤正常组织细胞，限制了其在临床上的应用。多酚类天然产物不仅可以提高肿瘤细胞的辐射敏感性，同时又能缓解辐射对机体产生的负面效应，在肿瘤治疗中发挥着重要作用。非编码RNA在许多疾病的发生发展中起着重要作用，近年来研究发现多酚类物质在抗肿瘤及辐射增敏方面与非编码RNA的调控存在一定关联。基于此，本文综述天然产物多酚抗肿瘤和辐射增敏的作用及其机制，并基于非编码RNA调控层面阐释其作用效果，以期为肿瘤等疾病的干预治疗及相关特医膳食食品的开发提供新思路。     

The powerful story against cardiovascular diseases: Dietary factors

Cardiovascular diseases are the underlying cause of most deaths worldwide, and they are expected to rise in the following years. Cardiovascular diseases include diseases that affect the heart, cerebral, and peripheral vessels, resulting in ischemia. On the basis of cardiovascular disease pathophysiology, there are lipoprotein metabolism abnormalities, oxidative stress, chronic inflammation, endothelium damage, and atherothrombosis. Modifiable risk factors for cardiovascular health and diseases are blood pressure, blood lipid profile, oxidative stress, inflammation, and other factors (smoking, obesity, diabetes mellitus). Atherosclerotic plaque development, vascular calcification, and vascular stiffness are caused by a long-term endothelial dysfunction and inflammatory response, which can be prevented and controlled by the diet. Fat and cholesterol are the commonly considered dietary factors in the association of the nutrition and the cardiovascular disease, although other macronutrients, especially carbohydrates and proteins, also have major effects. Nowadays, other macronutrients and micronutrients (minerals and vitamins) have roles in regulating the indicated processes (blood pressure, calcification, oxidative stress, inflammation, etc.) in cardiovascular disease prognosis. Other dietary compounds (sterols, stanols, polyphenols, carotenoids, etc.) that exist in small amounts in foods might have a role in regulating these mechanisms as well. There are also new insights about walnuts, garlic, ginger, and hawthorn as parts of a healthy diet against cardiovascular diseases. So far, there have not appeared any reviews that combine the impact of a wide variety of dietary components on cardiovascular diseases. Thus, the novel nutritional targets and interventions that focus on nutrients and other dietary compounds on potential mechanisms underlying cardiovascular diseases are discussed in this review.     

Inhibition of neointimal formation by trans‐resveratrol: Role of phosphatidyl inositol 3‐kinase‐dependent Nrf2 activation in heme oxygenase‐1 induction

Neointima, defined as abnormal growth of the intimal layer of blood vessels, is believed to be a critical event in the development of vascular occlusive disease. Although resveratrol's inhibitory effects on proliferation and migration of vascular smooth muscle cells has been reported, its activity on neointimal formation is still unclear. Oral administration of trans‐resveratrol significantly suppressed intimal hyperplasia in a wire‐injured femoral artery mouse model. In cultured vascular smooth muscle cells, trans‐resveratrol inhibited platelet‐derived growth factor‐stimulated DNA synthesis and cell proliferation with down‐regulation of cyclin D and pRB. Moreover, platelet‐derived growth factor‐induced production of reactive oxygen species was inhibited by trans‐resveratrol and the compound induced heme oxygenase‐1 (HO‐1). The anti‐proliferative activity of trans‐resveratrol was reversed by an HO‐1 inhibitor, ZnPPIX. Subcellular fractionation and reporter gene analyses revealed that trans‐resveratrol increased the level of nuclear Nrf2 and antioxidant response element reporter activity, and that these were essential for the induction of HO‐1. Trans‐resveratrol also enhanced the activities of phosphatidyl inositol 3‐kinase and extracellular signal regulated kinase, and phosphatidyl inositol 3‐kinase was required for Nrf2/antioxidant response element‐dependent HO‐1 induction. These data have significant implications for the elucidation of the pharmacological mechanism by which trans‐resveratrol prevents vascular occlusive diseases.     

SIRT3多酚激活剂的筛选及其对UVB诱导HaCaT细胞衰老的修复作用

沉默信息调节因子2相关酶类3（silent mating type information regulation 2 homolog 3,SIRT3）是位于线粒体基质中的一种去乙酰化酶,在线粒体能量代谢、氧化应激调节、延缓衰老等方面具有重要的作用。本研究通过采用SIRT3-EGFP报告基因系统及实时荧光定量聚合酶链式反应技术,从白藜芦醇、山柰酚、石榴皮鞣素、安石榴苷、漆树黄酮、咖啡醇、矢车菊素、飞燕草素葡萄糖苷这8 种多酚类化合物中筛选SIRT3激活剂,并评价筛选得到的SIRT3多酚激活剂对于中波紫外线（ultraviolet radiation B,UVB）诱导的人正常皮肤永生化角质形成细胞（human immortalized keratinocytes,HaCaT）衰老的抑制作用。结果表明,白藜芦醇、山柰酚、安石榴苷、漆树黄酮和咖啡醇具有显著增强SIRT3基因表达水平的作用（P＜0.05）;白藜芦醇、安石榴苷、漆树黄酮以及咖啡醇均能有效降低UVB诱导的细胞内活性氧水平;这5 种多酚均显著提高了谷胱甘肽（reduced glutathione,GSH）/氧化型谷胱甘肽（oxidized glutathione,GSSG）比值（P＜0.05）,白藜芦醇与咖啡醇显著增强了超氧化物歧化酶2活性（P＜0.05、P＜0.01）;此外,安石榴苷不仅可以激活SIRT3,修复细胞的抗氧化系统,且显著降低了细胞衰老标志物SA-β-gal的相对活力（P＜0.05）。结论：白藜芦醇、山柰酚、安石榴苷、漆树黄酮和咖啡醇均能激活SIRT3基因的表达,其中安石榴苷能够显著修复UVB诱导的HaCaT细胞衰老,其抗衰老机制可能与SIRT3-烟酰胺腺嘌呤二核苷酸磷酸-GSH/GSSG抗氧化途径有关。     

Resveratrol confers resistance against taxol via induction of cell cycle arrest in human cancer cell lines

Resveratrol, which is highly concentrated in the skin of grapes and is abundant in red wine, has been demonstrated to account for several beneficial properties, including antioxidant, anticoagulant, anti‐inflammatory and anticancer effects. Taxol is a microtubule‐stabilizing drug that has been extensively used as effective chemotherapeutic agents in the treatment of solid tumors. Here, we investigated whether the combination of the two compounds would yield increased antitumor efficacy in human cancer cells. Unexpectedly, resveratrol effectively prevented tumor cell death induced by taxol in 5637 bladder cancer cells. This pronounced antagonistic function of resveratrol against taxol was associated with changes in multiple signal transduction pathways, but not with tubulin polymerization. Importantly, cell cycle analysis showed that resveratrol prevented the cells from entering into mitosis, the phase in which taxol exerts its action. Furthermore, resveratrol blocked the cytotoxic effects of vinblastine but not cisplatin in 5637 cells. Interestingly, resveratrol pre‐treatment followed by taxol resulted in synergistic cytotoxicity. Finally, we extended our studies to various human cancer cell lines. Taken together, our results indicate that resveratrol may have the potential to negate the therapeutic efficacy of taxol and suggest that consumption of resveratrol‐related products may be contraindicated during cancer therapy with taxol.     

Modulation of steroid activity in chronic inflammation: a novel anti-inflammatory role for curcumin

The expression of NF-kappaB (NF-kappaB)-dependent pro-inflammatory genes in response to oxidative stress is regulated by the acetylation-deacetylation status of histones bound to the DNA. It has been suggested that in severe asthma and in chronic obstructive pulmonary disease (COPD) patients, oxidative stress not only activates the NF-kappaB pathway but also alters the histone acetylation and deacetylation balance via post-translational modification of histone deacetylases (HDACs). Corticosteroids have been one of the major modes of therapy against various chronic respiratory diseases such as asthma and COPD. Failure of corticosteroids to ameliorate such disease conditions has been attributed to their inability to either recruit HDAC2 or to the presence of an oxidatively modified HDAC2 in asthmatics and COPD subjects. Naturally occurring polyphenols such as curcumin and resveratrol have been increasingly considered as safer nutraceuticals. Curcumin is a polyphenol present in the spice turmeric, which can directly scavenge free radicals such as superoxide anion and nitric oxide and modulate important signaling pathways mediated via NF-kappaB and mitogen-activated protein kinase pathways. Polyphenols also down-regulate expression of pro-inflammatory mediators, matrix metalloproteinases, adhesion molecules, and growth factor receptor genes and they up-regulate HDAC2 in the lung. Thus, curcumin may be a potential antioxidant and anti-inflammatory therapeutic agent against chronic inflammatory lung diseases.     

Health benefits of walnut polyphenols: An exploration beyond their lipid profile

Walnuts are commonly found in our diet and have been recognized for their nutritious properties for a long time. Traditionally, walnuts have been known for their lipid profile, which has been linked to a wide array of biological properties and health-promoting effects. In addition to essential fatty acids, walnuts contain a variety of other bioactive compounds, such as vitamin E and polyphenols. Among common foods and beverages, walnuts represent one of the most important sources of polyphenols, hence their effect over human health warrants attention. The main polyphenol in walnuts is pedunculagin, an ellagitannin. After consumption, ellagitannins are hydrolyzed to release ellagic acid, which is converted by gut microflora to urolithin A and other derivatives such as urolithins B, C, and D. Ellagitannins possess well known antioxidant and anti-inflammatory bioactivity, and several studies have assessed the potential role of ellagitannins against disease initiation and progression, including cancer, cardiovascular, and neurodegenerative diseases. The purpose of this review is to summarize current available information relating to the potential effect of walnut polyphenols in health maintenance and disease prevention.