PMID- 32111491 OWN - NLM STAT- MEDLINE DCOM- 20200916 LR - 20200916 IS - 1873-5487 (Electronic) IS - 0188-4409 (Linking) VI - 51 IP - 2 DP - 2020 Feb TI - Molecular Basis of the Beneficial Actions of Resveratrol. PG - 105-114 LID - S0188-4409(19)31329-3 [pii] LID - 10.1016/j.arcmed.2020.01.010 [doi] AB - Resveratrol modulates the transcription factor NF-kappaB, cytochrome P450 isoenzyme CYP1A1, expression and activity of cyclooxygenase (COX) enzymes, Fas/Fas ligand mediated apoptosis, p53, mTOR and cyclins and various phospho-diesterases resulting in an increase in cytosolic cAMP levels. Cyclic AMP, in turn, activates Epac1/CaMKKbeta/AMPK/SIRT1/PGC-1alpha pathway that facilitates increased oxidation of fatty acids, mitochondrial respiration and their biogenesis and gluconeogenesis. Resveratrol triggers apoptosis of activated T cells and suppresses tumor necrosis factor-alpha (TNF-alpha), interleukin-17 (IL-17) and other pro-inflammatory molecules and inhibits expression of hypoxia inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) that may explain its anti-inflammatory actions. Polyunsaturated fatty acids (PUFAs) and their anti-inflammatory metabolites lipoxin A4, resolvins, protectins and maresins have a significant role in obesity, type 2 diabetes mellitus (T2DM), metabolic syndrome and cancer. We observed that PUFAs (especially arachidonic acid, AA) and BDNF (brain-derived neurotrophic factor) protect against the cytotoxic actions of alloxan, streptozotocin, benzo(a)pyrene (BP) and doxorubicin. Thus, there is an overlap in the beneficial actions of resveratrol, PUFAs and BDNF suggesting that these molecules may interact and augment synthesis and action of each other. This is supported by the observation that resveratrol and PUFAs modulate gut microbiota and influence stem cell proliferation and differentiation. Since resveratrol is not easily absorbed from the gut it is likely that it may act on endocannabinoid and light, odor, and taste receptors located in the gut, which, in turn, convey their messages to the various organs via vagus nerve. CI - Copyright (c) 2020 IMSS. Published by Elsevier Inc. All rights reserved. FAU - Repossi, Gaston AU - Repossi G AD - Instituto de Investigaciones en Ciencias de la Salud, Catedra de Biologia Celular, Histologia y Embriologia, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Ciudad Universitaria, Cordoba, Argentina. FAU - Das, Undurti N AU - Das UN AD - UND Life Sciences, Battle Ground, Washington, USA. Electronic address: Undurti@hotmail.com. FAU - Eynard, Aldo Renato AU - Eynard AR AD - Instituto de Investigaciones en Ciencias de la Salud, Catedra de Biologia Celular, Histologia y Embriologia, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Ciudad Universitaria, Cordoba, Argentina. LA - eng PT - Journal Article PT - Review DEP - 20200226 PL - United States TA - Arch Med Res JT - Archives of medical research JID - 9312706 RN - 0 (Antioxidants) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Fatty Acids, Unsaturated) RN - 7171WSG8A2 (BDNF protein, human) RN - Q369O8926L (Resveratrol) SB - IM MH - Antioxidants/pharmacology/*therapeutic use MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Fatty Acids, Unsaturated/*metabolism MH - Humans MH - Resveratrol/pharmacology/*therapeutic use OTO - NOTNLM OT - Brain-derived neurotrophic factor OT - Cancer OT - Cytotoxic OT - Lipoxin A4 OT - Metabolic syndrome OT - Polyunsaturated fatty acids OT - Resveratrol EDAT- 2020/03/01 06:00 MHDA- 2020/09/17 06:00 CRDT- 2020/03/01 06:00 PHST- 2019/12/31 00:00 [received] PHST- 2020/01/24 00:00 [accepted] PHST- 2020/03/01 06:00 [pubmed] PHST- 2020/09/17 06:00 [medline] PHST- 2020/03/01 06:00 [entrez] AID - S0188-4409(19)31329-3 [pii] AID - 10.1016/j.arcmed.2020.01.010 [doi] PST - ppublish SO - Arch Med Res. 2020 Feb;51(2):105-114. doi: 10.1016/j.arcmed.2020.01.010. Epub 2020 Feb 26.