Resveratrol, a polyphenol found in numerous plant species, including mulberries, peanuts and grapes, has shown to possess chemopreventive properties against several cancers, and cardiovascular diseases. Recently, resveratrol has been shown to have positive effects on age longevity, lipid levels and a preventative quality against certain cancers and viral infections. Resveratrol induces apoptosis by up-regulating the expression of Bax, Bak, PUMA, Noxa, Bim, p53, TRAIL, TRAIL-R1/DR4 and TRAIL-R2/DR5 and simultaneously down-regulating the expression of Bcl-2, Bcl-XL, Mcl-1 and survivin. Resveratrol causes growth arrest at G1 and G1/S phases of cell cycle by inducing the expression of CDK inhibitors p21/WAF1/CIP1 and p27/KIP1. Resveratrol has also been shown to reduce inflammation via inhibition of prostaglandin production, cyclooxygenase-2 activity, and nuclear factor-кB activity. Modulation of cell signaling pathway by resveratrol explains its diverse bioactivities related with human health. Resveratrol also potentiates the apoptotic effects of cytokines, chemotherapeutic agents and gamma-radiation. Pharmacokinetic and pharmacodynamic studies demonstrated that the main target organs of resveratrol are liver and kidney, and it is metabolized by hydroxylation, glucuronidation, sulfation and hydrogenation. As a chemoprevention agent, resveratrol has been shown to inhibit tumor initiation, promotion, and progression. There is growing evidence that resveratrol can prevent or delay the onset of various cancers, heart diseases, ischemic and chemically induced injuries, pathological inflammation and viral infections. This review summarizes the molecular mechanisms of resveratrol and its clinical benefits for human diseases.
INTRODUCTION
Resveratrol (C14H12O3) is a naturally occurring phytoalexin produced by some higher plants in response to stress/injury due to environmental hazards. Phytoalexins are chemical substances produced by plants as a defense against infection by pathogenic microorganisms such as fungi. The polyphenolic compound resveratrol, which is also known as 3,4′,5 trihydroxystilbene and 3,4′,5-stilbenetriol (Figure 1), exists in cis-and trans-stereoisomeric forms commonly found in grapes and wines particularly red wine (Figure 2). Trans-resveratrol can undergo isomerization to the cis-form when heated or exposed to ultraviolet irradiation. It is synthesized from p-coumaroyl CoA and malonyl CoA (Figure 3). It is a naturally occurring phytochemical found in many plant species, including grapes, peanuts and various herbs and it is the parent molecule of a family of polymers called viniferins.
The age-adjusted incidence of cancer has been increasing by approximately 3% annually worldwide (1). Many risk factors for human cancer have been proposed, including genetic predisposition, age, diet, hormones, and environmental factors. However, its etiology is still largely unknown. The importance of prevention in reducing the morbidity and mortality from cancer has been widely recognized. A promising avenue for future clinical chemoprevention studies focuses on phytochemicals/phytoalexins, as a means of cancer preventive compounds, find in fruits, vegetables and other plants. Many phytochemicals are excellent potential chemopreventive agents, because, in addition to their cancer preventive effects, they are relatively non-toxic, natural and inexpensive, they can be taken orally and may have additional health benefits. New opportunities in clinical chemoprevention research include investigating the chemopreventive effects of phytochemicals and conducting studies in patients with cancer. There is also a great need to investigate potential benefits and risks of administering phytochemicals/natural compounds before, during or after conventional therapies, such as surgery, chemotherapy, radiation or hormonal therapy. In addition, administration of chemo preventive agents prior to surgery provides an opportunity to investigate the modulation of genetic and epigenetic pathways by putative cancer preventive compounds and nutrients.
While many new classes of cancer chemopreventive agents are being evaluated in clinical trials for other malignancies, little success has been achieved so far. Chemoprevention of cancer is a means of cancer control where the occurrence of disease can be entirely prevented, slowed or reversed by the administration of one or a combination of naturally occurring or synthetic compounds (2, 3). The overall goal of this modality is to reduce cancer incidence and multiplicity in the first place. The chemopreventive compounds are also known as anticarcinogens where the preventive approach includes intervention (or secondary prevention) of the conversion of precancerous lesions into malignant carcinomas (3).
Resveratrol has been shown to have anti-inflammatory, antioxidant, antitumor, neuroprotective, and immunomodulatory activities (4-6). It also has activity in the regulation of multiple cellular events associated with carcinogenesis. Resveratrol has also been examined in several model systems for its potential effect against cancer (7-9). Its anticancer effects include its role as a chemopreventive agent, its ability to inhibit cell proliferation, its direct effect in cytotoxicity by induction of apoptosis and on its potential therapeutic effect in pre-clinical studies (10, 11). It induces growth arrest and apoptosis through regulation of multiple signaling pathways. The purpose of this review is to summarize the molecular mechanisms of resveratrol and assess its therapeutic potential for human diseases.
MECHANISM OF ACTION
Regulation of Bcl-2 family members
The Bcl-2 proto-oncogene was discovered at the chromosomal breakpoint of t(14;18) bearing humanB-cell lymphomas. The Bcl-2 family of proteins has expanded significantlyand includes both pro- as well as anti-apoptotic molecules (Figure 4). Some of the members of this family (e.g. Bcl-2 and Bcl-XL) inhibit apoptosis, and while others (e.g. Bcl-XS, Bax and Bak) promote apoptosis (12-15). Indeed,the ratio between these two subsets helps determine, in part,the susceptibility of cells to a death signal (16). An additional characteristic of the members of this family is their frequent ability to form homo- as well as hetero-dimers,suggesting neutralizing competition between these proteins. Furthermore, these members have ability to become integral membraneproteins and regulate several physiological events.
Bcl-2 family members possess up to four conserved Bcl-2 homology (BH) domains designated BH1, BH2, BH3, and BH4, which correspondto α-helical segments (17-19). Many of the anti-apoptotic members display sequence conservation in all four domains. The pro-apoptoticmolecules frequently display less sequence conservation of thefirst α-helical segment, BH4. Deletion and mutagenesis studiesargue that the amphipathic α-helical BH3 domain serves as a criticaldeath domain in the pro-apoptotic members. This concept is supportedby an emerging subset of “BH3-domain-only” members who displaysequence homology only within the BH3 domain and to date are allpro-apoptotic. However, the three-dimensional structure of atleast one BH3-domain-only molecule, BID, demonstrates a very similaroverall α-helical content to the anti-apoptotic molecule Bcl-XL(20). Many Bcl-2 family membersalso contain a carboxy-terminal hydrophobic domain, which in thecase of Bcl-2 is essential for its targeting to membranes suchas the mitochondrial outer membrane. Overexpression of Bcl-2 and Bcl-XL protein protects a wide variety of cells from many death-inducing stimuli (21-24). Resveratrol inhibits the expression of antiapoptotic proteins such as Bcl-2 and Bcl-XL, and induces the expression of Bax, Bak, Bad, PUMA, Noxa and Bim (25-30). These data suggest that the regulation of Bcl-2 family members plays a major role in resveratrol-induced apoptosis.
Regulation of Cell Cycle
Resveratrol has been reported to modulate cell cycle and to induce apoptosis. Several authors have studied the effect of the stilbene on cell cycle-control. In colon cancer cells, a down-regulation of the cyclin D1/Cdk4 complex has been reported (31), while in transplantable liver cancer H22 cells, resveratrol decreased cyclin B1 and Cdc2 protein, although no alteration of cyclin D1 was observed, G2 arrest was itself been reported to be linked with the inhibition of Cdk7 and Cdc2. In addition, an S-phase arrest was also been noticed in melanoma cells, being related to cyclins A, E, and B1 (32). Thus, it is clear that the effects of resveratrol on cell cycle are highly variable, depending on the cell line observed. An additional complexity level occurs, related to a dose-dependent action of resveratrol on DNA synthesis (32), and attributed to the modulation of nuclear p21/Cip1/WAF1 and p27/Kip1 levels. Our data indicate a decrease (at nanomolar resveratrol concentrations) of DNA synthesis, and therefore a decrease of cells entering S-phase, suggesting that the p21 pathway may not be involved in its action. However, the observed accumulation of cells in G1 could also imply the Rb or the p53 pathways. Indeed, it was shown that resveratrol treatment of melanoma cells resulted in reduced hyperphosphorylated Rb and an increased hypophosphorylated Rb. This response was accompanied by down-regulation of the expression of all five E2F family transcription factors and their heterodimeric partners DP1 and DP2, introducing an arrest of cell-cycle progression at the G1/S phase transition, thereby leading to subsequent apoptotic cell death. In addition, in melanoma (33), endothelial (34) and fibroblastic cell lines (35), resveratrol treatment led to an activation of p53 activity, which correlated with suppression of cell progression through the S and G2 phases of the cell-cycle and apoptosis The effect of resveratrol on the G2-phase of cell cycle could be due to the action of resveratrol on the cytoskeleton (36). Catechin oligomers, acting on membrane androgen receptors could, induce apoptosis, through actin filaments rearrangement. Overall, these data suggest that resveratrol causes growth arrest at G1, G/S and G2 phase of the cell cycle.
Resveratrol causes growth arrest at G1 and G1/S phases of cell cycle by inducing the expression of CDK inhibitors p21/WAF1/CIP1 and p27/KIP1.
Resveratrol has also been shown to reduce inflammation via inhibition of prostaglandin production, cyclooxygenase-2 activity, and nuclear factor-кB activity.
New opportunities in clinical chemoprevention research include investigating the chemopreventive effects of phytochemicals and conducting studies in patients with cancer.
Chemoprevention of cancer is a means of cancer control where the occurrence of disease can be entirely prevented, slowed or reversed by the administration of one or a combination of naturally occurring or synthetic compounds (2, 3).
The chemopreventive compounds are also known as anticarcinogens where the preventive approach includes intervention (or secondary prevention) of the conversion of precancerous lesions into malignant carcinomas (3).Resveratrol has been shown to have anti-inflammatory, antioxidant, antitumor, neuroprotective, and immunomodulatory activities (4-6).
An additional characteristic of the members of this family is their frequent ability to form homo- as well as hetero-dimers,suggesting neutralizing competition between these proteins.
Chemoprevention by tocotrienol 400mg : Buy online Delta Gold tocotrienols 400mg with Anticancer Properties Of Tocotrienol 400 mg contains 90 % Delta Gold Tocotrienols and 10% Gamma | Eannatto.in
The global Resveratrol Market research report, published by Value Market Research, is designed to offer various market framework such as market size, portion, trends, growth path, value and factors that impact the current market dynamics over the forecast period 2020-2027.
Most importantly, this report also provides the latest significant strategies adopted by major players along with their market share.The research report also covers the comprehensive profiles of the key players in the market and an in-depth view of the competitive landscape worldwide.
The major players in the resveratrol market include DSM Nutritionals, Evolva, Endurance Product Company, Great Forest Biomedical, Laurus Labs Limited, JF-NATURAL, MAYPRO Industries, Sabinsa Corporation, Resvitale LLC, Shanghai Natural Bio-engineering Co., Ltd..
This section consists of a holistic view of the competitive landscape that includes various strategic developments such as key mergers & acquisitions, future capacities, partnerships, financial overviews, collaborations, new product developments, new product launches, and other developments.Get more information on "Global Resveratrol Market Research Report" by requesting FREE Sample Copy at https://www.valuemarketresearch.com/contact/resveratrol-market/download-sampleMarket Dynamics Resveratrol is gaining demand due to the aging population and increased prevalence of chronic and life-threatening diseases.
Resveratrol has grabbed a lot of attention for its reported anti-aging and disease-fighting powers.
There has been robust research on resveratrol to explore its potential.
Bioinformatics is increasingly being used to identify genes in DNA sequences.
This assists in developing better treatments and diagnostic tests.
Recently, due to significant reductions in costs of sequencing, many scientific research institutes and biotech companies have undertaken initiatives to perform sequencing studies at their own facilities.Major Growth Drivers:Growth of the bioinformatics market is driven by the growing demand for nucleic acid and protein sequencing, increasing government initiatives and funding, and increasing use of bioinformatics in drug discovery and biomarker development processes.
With the introduction of upcoming technologies such as nanopore sequencing (third generation sequencing technique) and cloud computing, the market is expected to offer significant opportunities for manufacturers of bioinformatics solutions.Expected Revenue Growth:[195 Pages Report] The global bioinformatics market is expected to account for USD 7,063.7 billion in 2018.
It is expected to reach USD 13,901.5 billion by 2023, at a CAGR of 14.5% during the forecast period.Accessories to Fuel the Growth of Bioinformatics Market :Bioinformatics is the application of computer technology for the management and analysis of biological data.
It includes collection, storage, retrieval, manipulation, and modelling of data for analysis, visualization, or prediction through algorithms and software.However, factors such as a dearth of skilled personnel to ensure proper use of bioinformatics tools and lack of integration of a wide variety of data generated through various bioinformatics platforms are hindering market growth.Browse in-depth TOC on “Bioinformatics Market”189 – Tables27 – Figures195 – PagesDownload PDF Brochure: https://www.marketsandmarkets.com/pdfdownloadNew.asp?id=39By Product and Services, bioinformatics platforms segment is expected to be the fastest-growing segment in the forecast periodKnowledge management tools commanded the largest market share in the global bioinformatics market in 2018, while the bioinformatics platforms segment is expected to be the fastest-growing segment in the forecast period.
