title: (7R,8S)-Dehydrodiconiferyl Alcohol Suppresses Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglia by Inhibiting MAPK Signaling.
abstract: (7R,8S)-Dehydrodiconiferyl alcohol (DDA), a lignan isolated from the dried stems of Clematis armandii, has been found to exert potential anti-inflammatory activity in vitro. In the present study, we investigated the effects and possible mechanisms of DDA on lipopolysaccharide (LPS)-mediated inflammatory response in murine BV2 microglia. Our results revealed that non-toxic concentrations (6.25-25 μM) of DDA markedly suppressed LPS-induced production of nitric oxide, expression of inducible nitric oxide synthase and cyclooxygenase-2, and release of inflammatory factors, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in a concentration dependent manner. In addition, DDA time- and concentration-dependently attenuated LPS-induced phosphorylation of c-Jun N-terminal kinase 1/2 (JNK), but not protein kinase B, p38, or extracellular signal-regulated kinase 1/2. Moreover, DDA significantly suppress LPS-mediated nuclear factor-κB (NF-κB) activation by inhibiting phosphorylation and nuclear translocation of NF-κB p65. Collectively, our results demonstrated that DDA inhibited LPS-stimulated inflammatory response in BV2 cell, at least in part, through inhibition of NF-κB activation and modulation of JNK signaling.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, 826, Zhangheng Road, Pudong New District, Shanghai, 201203, China.
authors.forename: Si-Yu
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, 826, Zhangheng Road, Pudong New District, Shanghai, 201203, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, 826, Zhangheng Road, Pudong New District, Shanghai, 201203, China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Luo
authors.affiliation: Department of Natural Products Chemistry, School of Pharmacy, Fudan University, Shanghai, 201203, China. jfhu@fudan.edu.cn.
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, 826, Zhangheng Road, Pudong New District, Shanghai, 201203, China. liuxinhua@fudan.edu.cn.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Liu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000201:enzymology*; D010636:Phenols / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D010636:Phenols; C080686:dehydrodiconiferyl alcohol
keywords: (7R,8S)-Dehydrodiconiferyl alcohol; BV2 microglia; Inflammation; Lipopolysaccharide; c-jun N-terminal kinase 1/2