title: Anti-inflammatory mechanism of α-viniferin regulates lipopolysaccharide-induced release of proinflammatory mediators in BV2 microglial cells.
abstract: α-Viniferin is an oligostilbene of trimeric resveratrol and has anticancer activity; however, the molecular mechanism underlying the anti-inflammatory effects of α-viniferin has not been completely elucidated thus far. Therefore, we determined the mechanism by which α-viniferin regulates lipopolysaccharide (LPS)-induced expression of proinflammatory mediators in BV2 microglial cells. Treatment with α-viniferin isolated from Clematis mandshurica decreased LPS-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2). α-Viniferin also downregulated the LPS-induced expression of proinflammatory genes such as iNOS and COX-2 by suppressing the activity of nuclear factor kappa B (NF-κB) via dephosphorylation of Akt/PI3K. Treatment with a specific NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), indirectly showed that NF-κB is a crucial transcription factor for expression of these genes in the early stage of inflammation. Additionally, our results indicated that α-viniferin suppresses NO and PGE2 production in the late stage of inflammation through induction of heme oxygenase-1 (HO-1) regulated by nuclear factor erythroid 2-related factor (Nrf2). Taken together, our data indicate that α-viniferin suppresses the expression of proinflammatory genes iNOS and COX-2 in the early stage of inflammation by inhibiting the Akt/PI3K-dependent NF-κB activation and inhibits the production of proinflammatory mediators NO and PGE2 in the late stage by stimulating Nrf2-mediated HO-1 signaling pathway in LPS-stimulated BV2 microglial cells. These results suggest that α-viniferin may be a potential candidate to regulate LPS-induced inflammation.
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Ara-1 dong, Jeju 690-756, Republic of Korea.
authors.forename: Matharage Gayani
authors.initials: MG
authors.lastname: Dilshara
authors.affiliation: Division of Wood Chemistry & Microbiology, Department of Forest Products, Korea Forest Research Institute, 57 Hoegiro, Dongdaemun-gu, Seoul 130-712, Republic of Korea.
authors.forename: Kyoung-Tae
authors.initials: KT
authors.lastname: Lee
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Ara-1 dong, Jeju 690-756, Republic of Korea.
authors.forename: Hee Ju
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Division of Wood Chemistry & Microbiology, Department of Forest Products, Korea Forest Research Institute, 57 Hoegiro, Dongdaemun-gu, Seoul 130-712, Republic of Korea.
authors.forename: Hak-Ju
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan 614-050, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Lee
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Lark Kyun
authors.initials: LK
authors.lastname: Kim
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Ara-1 dong, Jeju 690-756, Republic of Korea. Electronic address: immunkim@jejunu.ac.kr.
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D002460:Cell Line; D039324:Clematis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000276:immunology; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D017628:Microglia / Q000276:immunology*; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D010936:Plant Extracts; D018517:Plant Roots; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000276:immunology; D011759:Pyrrolidines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D013859:Thiocarbamates / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001572:Benzofurans; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D051547:Heme Oxygenase-1; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; D011759:Pyrrolidines; D034741:RNA, Small Interfering; D013859:Thiocarbamates; C495636:Nfe2l2 protein, mouse; C020972:pyrrolidine dithiocarbamic acid; C064176:alpha-viniferin; C496317:Nos2 protein, mouse; C496542:Hmox1 protein, mouse; C077623:Ptgs2 protein, mouse
keywords: Nitric oxide; Nuclear factor erythroid 2-related factor; Nuclear factor-κB; Prostaglandin E(2); α-Viniferin