title: Beneficial action of resveratrol: How and why?
abstract: Flavonoid resveratrol modulates the transcription factor NF-κB; inhibits the cytochrome P450 isoenzyme CYP1 A1; suppresses the expression and activity of cyclooxygenase enzymes; and modulates Fas/Fas-ligand-mediated apoptosis, p53, mammalian target of rapamycin, and cyclins and various phosphodiesterases. This increases the cytosolic cAMP that activates Epac1/CaMKKβ/AMPK/SIRT1/PGC-1α pathway, which in turn facilitates increased oxidation of fatty acids, mitochondrial biogenesis, mitochondrial respiration, and gluconeogenesis. Resveratrol triggers apoptosis of activated T cells and suppresses tumor necrosis factor-α, interluekin-17 (IL-17), and other proinflammatory molecules, and thus is of benefit in autoimmune diseases. In addition, resveratrol inhibits expression of hypoxia-inducible factor-1α and vascular endothelial growth factor, explaining its effective action against cancer. Brain-derived neurotrophic factor (BDNF) that is involved in the pathogenesis of obesity, type 2 diabetes mellitus, and metabolic syndrome is also altered in depression, schizophrenia, bipolar disorder, and autism. We noted that BDNF protects against cytotoxic actions of alloxan, streptozotocin, and benzo(a)pyrene. Resveratrol prevents bisphenol A-induced autism, type 2 diabetes mellitus, and metabolic syndrome, suggesting that it may augment BDNF synthesis and action. We also observed that BDNF levels are low in type 2 diabetes mellitus and that BDNF enhances production of antiinflammatory lipid, lipoxin A4, whose levels are low in diabetes mellitus. Thus, resveratrol may augment production of lipoxin A4. Resveratrol alters gut microbiota and influences stem cell proliferation and differentiation. These pleiotropic actions of resveratrol may explain the multitude of its actions and benefits.
authors.affiliation: Biología Celular, Histología y Embriología, Facultad de Ciencias Médicas, INICSA (CONICET-Universidad Nacional de Córdoba), Córdoba, Argentina.
authors.forename: Gustavo Tomas
authors.initials: GT
authors.lastname: Diaz-Gerevini
authors.affiliation: Biología Celular, Histología y Embriología, Facultad de Ciencias Médicas, INICSA (CONICET-Universidad Nacional de Córdoba), Córdoba, Argentina; Cátedra de Histología, Embriología y Genética, Universidad Nacional de La Rioja, La Rioja, Argentina; CONICET, Córdoba, Argentina.
authors.forename: Gaston
authors.initials: G
authors.lastname: Repossi
authors.affiliation: Biología Celular, Histología y Embriología, Facultad de Ciencias Médicas, INICSA (CONICET-Universidad Nacional de Córdoba), Córdoba, Argentina.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Dain
authors.affiliation: CONICET, Córdoba, Argentina; Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: María Cristina
authors.initials: MC
authors.lastname: Tarres
authors.affiliation: Department of Medicine, GVP Hospital and BioScience Research Centre, Campus of Gayatri Vidya Parishad College of Engineering, Visakhapatnam, India; UND Life Sciences, Federal Way, Washington, USA.
authors.forename: Undurti Narasimha
authors.initials: UN
authors.lastname: Das
authors.affiliation: Biología Celular, Histología y Embriología, Facultad de Ciencias Médicas, INICSA (CONICET-Universidad Nacional de Córdoba), Córdoba, Argentina; CONICET, Córdoba, Argentina. Electronic address: aeynard@gmail.com.
authors.forename: Aldo Renato
authors.initials: AR
authors.lastname: Eynard
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001321:Autistic Disorder / Q000139:chemically induced / Q000517:prevention & control; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000517:prevention & control; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000382:microbiology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D044045:Lipoxins / Q000494:pharmacology; D024821:Metabolic Syndrome / Q000139:chemically induced / Q000517:prevention & control; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D019208:Brain-Derived Neurotrophic Factor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020381:Interleukin-17; D044045:Lipoxins; D016328:NF-kappa B; D013267:Stilbenes; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C040527:lipoxin A4; D019363:Cytochrome P-450 CYP1A1; D000077185:Resveratrol
keywords: Alzheimer's disease; Flavonoids; Microbiota; Obesity; Resveratrol; Type 2 diabetes mellitus