title: New compound, 5-O-isoferuloyl-2-deoxy-D-ribono-γ-lacton from Clematis mandshurica: Anti-inflammatory effects in lipopolysaccharide-stimulated BV2 microglial cells.
abstract: Microglia are main immune cells to exacerbate neural disorders in persistent overactivating. Therefore, it is a good strategy to regulate microglia for the treatment of neural disorders. In the present study, we isolated and characterized a novel compound, 5-O-isoferuloyl-2-deoxy-D-ribono-γ-lacton (5-DRL) from Clematis mandshurica, and evaluated its anti-inflammatory effect in lipopolysaccharide (LPS)-treated BV2 microglial cells. 5-DRL inhibited the expression of LPS-stimulated proinflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2), as well as their regulatory genes inducible NO syntheses (iNOS) and cyclooxygenase-2 (COX-2). 5-DRL also downregulated the LPS-induced DNA-binding activity of nuclear factor-κB (NF-κB) through suppression of the nuclear translocation of the NF-κB subunits, p65 and p50. Consistent with the inhibition of iNOS and COX-2 via NF-κB activity with 5-DRL, an inhibitor of NF-κB, pyrrolidine dithiocarbamate (PDTC), also led to the suppression of LPS-induced iNOS and COX-2 expression. Additionally, 5-DRL corresponding with antioxidants, N-acetylcysteine (NAC) and glutathione (GSH), remarkably inhibited reactive oxygen species (ROS) generation. Both NAC and GSH, thus attenuated the expression of iNOS and COX-2 by suppressing NF-κB activation, indicating that 5-DRL suppresses LPS-induced iNOS and COX-2 expression through downregulation of the ROS-dependent NF-κB signaling pathway. The present study also indicated that 5-DRL suppresses NO and PGE2 production by inducing heme oxygenase-1 (HO-1) via nuclear factor erythroid 2-related factor 2 (Nrf2). Taken together, the present data indicate that 5-DRL attenuates the production of proinflammatory mediators such as NO and PGE2 as well as their regulatory genes in LPS-stimulated BV2 microglial cells by inhibiting ROS-dependent NF-κB activation and stimulating the Nrf2/HO-1 signal pathway. These data may be implicated in the application of 5-DRL in LPS-stimulated inflammatory disease.
authors.affiliation: Department of Marine Life Sciences, Jeju National University, 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, Republic of Korea.
authors.forename: Kyoung-Tae
authors.initials: KT
authors.lastname: Lee
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 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: Division of Wood Chemistry & Microbiology Department of Forest Products, Korea Forest Research Institute, Republic of Korea.
authors.forename: Hak-Ju
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Microbiology, College of Medicine, Inje University, Busan 614-735, Republic of Korea. Electronic address: cihima@inje.ac.kr.
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
authors.affiliation: Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea. Electronic address: immunkim@jejunu.ac.kr.
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002461:Cell Line, Transformed; D039324:Clematis; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000276:immunology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009422:Nervous System Diseases / Q000188:drug therapy*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D008517:Phytotherapy; D018517:Plant Roots; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012266:Ribose / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013859:Thiocarbamates / Q000494:pharmacology
chemical_list: C000601181:5-O-isoferuloyl-2-deoxyribono-gamma-lactone; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007783:Lactones; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; D013859:Thiocarbamates; C066229:prolinedithiocarbamate; D009569:Nitric Oxide; D012266:Ribose; D011392:Proline; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D000111:Acetylcysteine
keywords: 5-O-isoferuloyl-2-deoxy-D-ribono-γ-lacton; Nitric oxide; Nuclear factor erythroid 2-related factor 2; Nuclear factor-κB; Prostaglandin E(2); Reactive oxygen species