title: Inhibitory effects of a spinasterol glycoside on lipopolysaccharide-induced production of nitric oxide and proinflammatory cytokines via down-regulating MAP kinase pathways and NF-κB activation in RAW264.7 macrophage cells.
abstract: Extracts from the leaves of Stewartia koreana are known to exhibit strong anti-inflammatory activity. Investigation of bioactive compounds from S. koreana has led to the isolation of 3-O-β-d-glucopyanosylspinasterol (spinasterol-Glc), a spinasterol glycoside. In the present study, we examined the effects of spinasterol-Glc on production of nitric oxide (NO) and proinflammatory cytokines in LPS-treated RAW264.7 macrophage cells and in mouse models. Our results showed that spinasterol-Glc inhibited the production of NO and proinflammatory cytokines such as TNF-α, IL-6 and IL-1β in dose-dependent manners in LPS-treated RAW264.7 cells. Spinasterol-Glc inhibited the expression of iNOS and the proinflammatory cytokine genes. Spinasterol-Glc also inhibited phosphorylation of IκB-α and IKKα/β as well as translocation of NF-κB to the nucleus. We demonstrated that spinasterol-Glc reduced transcription of the NF-κB minimal promoter and NF-κB DNA binding activity. Administration of the spinasterol-Glc significantly decreased the plasma levels of these inflammatory mediators including TNF-α, IL-6 and IL-1β in LPS-injected mice and improved survival of septic mice with lethal endotoxemia. These results suggest that spinasterol-Glc has effective inhibitory effects on production of inflammatory mediators via inhibition of MAP kinases/NF-κB activities, and can be used as a potential anti-inflammatory agent for the prevention and treatment of inflammatory diseases.
authors.affiliation: College of Life Sciences, Kyung Hee University, Republic of Korea.
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Lee
authors.forename: Mira
authors.initials: M
authors.lastname: Jung
authors.forename: Myun-Ho
authors.initials: MH
authors.lastname: Bang
authors.forename: Dae Kyun
authors.initials: DK
authors.lastname: Chung
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology; D001483:Base Sequence; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D008297:Male; D055670:Medicine, Korean Traditional; D051379:Mice; D008810:Mice, Inbred C57BL; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013265:Stigmasterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D028242:Theaceae / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D006027:Glycosides; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D012333:RNA, Messenger; C031312:spinasterol; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D013265:Stigmasterol; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051550:I-kappa B Kinase