title: Cryptotanshinone inhibits LPS-induced proinflammatory mediators via TLR4 and TAK1 signaling pathway.
abstract: Cryptotanshinone (CTN), one of the major constituents of tanshinones, was investigated for anti-inflammatory activity in the murine macrophage cell line RAW 264.7. CTN inhibited the production of nitric oxide (NO) production, as well as expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated macrophages. Since CTN was considered as inhibiting LPS-triggered phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB activation, we consequently evaluated the expression of toll-like receptor 4 (TLR4) and CD14, as well as phosphorylation of TGF-β-activated kinase 1 (TAK1). CTN reduced the expression of CD14 and TLR4, and suppressed LPS-induced phosphorylation of TAK1. Furthermore, CTN significantly increased the survival rate against LPS challenge in D-galactosamine-sensitized mice, which was in line with in vitro results. These results suggested that CD14/TLR4 and TAK1 might be the potential molecular targets for addressing the protective effects of CTN on LPS-induced inflammatory effects in macrophages.
authors.affiliation: Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Lian
authors.forename: Ting
authors.initials: T
authors.lastname: Bai
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Wu
authors.forename: Ying
authors.initials: Y
authors.lastname: Wan
authors.forename: Wen-Xue
authors.initials: WX
authors.lastname: Xie
authors.forename: Xuejun
authors.initials: X
authors.lastname: Jin
authors.forename: Ji-Xing
authors.initials: JX
authors.lastname: Nan
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology*; D010766:Phosphorylation; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D051198:Toll-Like Receptor 5 / Q000378:metabolism*; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D051546:Cyclooxygenase 2; D004365:Drugs, Chinese Herbal; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D020930:MAP Kinase Kinase Kinases; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D010616:Phenanthrenes; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D000099151:MAP Kinase Kinase Kinase 7; C493487:Tlr4 protein, mouse; C037886:cryptotanshinone; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse