RESVERATROL

Chemoprevention by resveratrol: molecular mechanisms and therapeutic potential.

A new study investigated the clinical benefits of resveratrol, a naturally occurring polyphenol identified in over 70 plant species including nuts, grapes, pine trees, certain vines and red wine, and found it to have cancer preventative (chemopreventative) properties.
Resveratrol is thought to play a role in the prevention of heart disease. A substantial amount of attention has been directed in recent years toward resveratrol for its potential health benefits in humans due to investigation of the French paradox that coronary heart disease mortality in France is lower than observed in other industrialized countries with a similar risk factor profile due to the frequent consumption of red wine.
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-kappaB 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.
Resveratrol has been shown in animal and laboratory studies to exhibit antioxidant, anticancer, antiproliferative, antifungal, antiviral and antibacterial effects. Being a constituent of grapes and wines, initial work was focused on linking resveratrol to the beneficial cardiovascular effects of moderate wine intake. However, studies have expanded to examine its effects in a variety of conditions, including various cancers, bacterial infections, fungal infections, viral infections, amyotrophic lateral sclerosis, diabetic polyneuropathy, Alzheimer's disease, Parkinson's disease, chronic obstructive pulmonary disease (COPD) and acute pancreatitis.
Researchers from the University of Texas Health Science Center noted that resveratrol has been 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 has also been shown to reduce inflammation via inhibition of prostaglandin production, cyclooxygenase-2 activity and nuclear factor-kappaB 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 the 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.
The review authors concluded that 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.
References:
1) Shankar S, Singh G, Srivastava RK. Chemoprevention by resveratrol: molecular mechanisms and therapeutic potential. Front Biosci. 2007 Sep 1;12:4839-54.

Resveratrol, a natural chemopreventive agent against degenerative diseases.

Ignatowicz E, Baer-Dubowska W.
Department of Pharmaceutical Biochemistry, Karol Marcinkowski University of Medical Sciences, Pozna, Poland.

Resveratrol (3,5,4'-trihydroxystilbene) is a naturally occurring compound shown to modulate the risk of cardiovascular degenerative diseases (atherosclerosis) and inhibit chemical carcinogenesis in rodents. Various studies have demonstrated the effect of this phytoalexin on biological mechanisms involved in cardioprotection. These include modulation of lipid turnover, inhibition of eicosanoid production, prevention of the low-density lipoprotein oxidation and inhibition of platelet aggregation. Carcinogenesis in animal models can be divided at least into three stages: initiation, promotion and progression. Initiation occurs as result of interaction of a reactive form of carcinogen with DNA. Chemical carcinogens like polycyclic aromatic hydrocarbons are metabolized to reactive species by cytochrome P450 dependent enzymes activated through aryl hydrocarbon (Ah) receptor. The inhibition of tumor initiation by resveratrol most probably occurs through preventing the activation of Ah receptor. Resveratrol affects also several factors involved in tumor promotion and progression. Since tumor promoting agents alter the expression of genes whose products are associated with inflammation, chemoprevention of cardiovascular diseases and cancer may share the same common mechanisms. This includes principally modulation of the expression of growth factors and cytokines. Recently, chemopreventive properties of resveratrol have been associated with the inhibition of NF-kappaB. This transcription factor is strongly linked to inflammatory and immune responses, regulation of cell proliferation and apoptosis, thus it is important for tumor development and many other diseases including atherosclerosis. Although the mechanisms by which resveratrol interferes with the activation of NF-KB are not clear, it seems that inhibition of its degradation which is necessary for its cellular activation is the principal target. Based on the quantity and diversity of data available on the biological activity of resveratrol, it has to be considered a very promising chemoprotector and chemotherapeutic. Urgent investigations on its bioavailability and effects on in vivo systems, especially in humans, are necessary.
Pol J Pharmacol. 2001 Nov-Dec;53(6):557-69.