Resveratrol: A nutrigenomic approach in new therapeutic challenges
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1
Aristotle University of Thessaloniki, Department of Pharmacology, Greece
Introduction: Resveratrol is a natural polyphenol mainly found in red grapes, berries, peanuts, pine and knotweed. It can directly modulate various molecules participating in signaling pathways implicated in the pathogenesis of cancer, cardiovascular disease and inflammation thus exhibiting anti-cancer, anti-inflammatory and cardioprotective properties.
Molecular targets. Cell survival: Resveratrol has been shown to upregulate SIRT1, a member of the NAD+ dependent deacetylase sirtuin protein family (SIRT1-7), which downregulates p53 activity thus preventing apoptosis and subsequent neurodegeneration. SITR1 activation also enhances mitochondrial function via PGC-1a deacetylation. Cardiovascular system: Resveratrol can inhibit MAPK, cPLA2 and TxA2 which results in inhibition of phospholipase C and protein kinase C and subsequent inhibition of platelet aggregation. Moreover, resveratrol can cause vasodilation via induction of endothelial and inducible NO synthase (eNOS, iNOS)expression. Resveratrol has also been shown to prevent atherosclerosis. Interestingly, resveratrol upregulates cholesterol efflux genes (ABCA1, ABCG1) and downregulates scavenger receptor AII(SR-AII) resulting in a decreased cholesterol accumulation in macrophages. Cell cycle regulation: Resveratrol can cause cell cycle arrest at G1/S phase by inducing p21WAF1 and p27KIP1 and downregulating cyclin D1/D2/E, Cdks 2/4/6 and hyperphosphorylated Rb and at G2/M phase by downregulating Cdk7 and p34Cdc2. Apoptosis: Resveratrol upregulates proapoptotic molecules such as p53, Bax, Bak, PUMA, Noxa, Bim and downregulates antiapoptotic molecules such as Bcl2, Bcl-XL, Mcl-1 thus inducing apoptosis. Resveratrol also facilitates apoptosis by increasing ceramide synthesis. Inflammation: Resveratrol inhibits COX-2 which is responsible for the production of prostaglandins from arachidonic acid.
Clinical implications. Resveratrol is a promising agent in the treatment of Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and brain damage caused by ischemia, strokes and epilepsy. Currently, resveratrol is being tested as a therapeutic agent in a wide variety of cancers including gliomas, meduloblastoma, prostate cancer, multiple myeloma, breast cancer and colon cancer.
Keywords:
resveratrol,
Nutrigenomics,
polyphenol,
therapy
Conference:
8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010, Thessaloniki, Greece, 1 Oct - 5 Oct, 2010.
Presentation Type:
Poster
Topic:
Nutrigenomics
Citation:
Kara
E,
Tsanakalis
F and
Papaioannidou
P
(2010). Resveratrol: A nutrigenomic approach in new therapeutic challenges.
Front. Pharmacol.
Conference Abstract:
8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010.
doi: 10.3389/conf.fphar.2010.60.00137
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Received:
28 Oct 2010;
Published Online:
04 Nov 2010.
*
Correspondence:
Dr. Paraskevi Papaioannidou, Aristotle University of Thessaloniki, Department of Pharmacology, Thessaloniki, Greece, ppap@auth.gr