title: Honokiol: an effective inhibitor of tumor necrosis factor-α-induced up-regulation of inflammatory cytokine and chemokine production in human synovial fibroblasts.
abstract: In this study, we investigated the mechanisms underlying the anti-inflammatory effects of honokiol in tumor necrosis factor (TNF)-α-stimulated rheumatoid arthritis synovial fibroblasts (RASFs). RASFs pre-treated with honokiol (0-20 μM) were stimulated with TNF-α (20 ng/ml). The levels of prostaglandin E2 (PGE2), nitric oxide (NO), soluble intercellular adhesion molecule-1 (sICAM-1), transforming growth factor-β1 (TGF-β1), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1α (MIP-1α) in supernatants were determined by enzyme-linked immunosorbent assay (ELISA) and Griess assay. In addition, protein expression levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and phosphorylated Akt, nuclear factor kappa B (NFκB), and extracellular signal-regulated kinase (ERK)1/2 were determined by western blot. The expression of NFκB-p65 was assessed by immunocytochemical analysis. TNF-α treatment significantly up-regulated the levels of PGE2, NO, sICAM-1, TGF-β1, MCP-1, and MIP-1α in the supernatants of RASFs, increased the protein expression of COX-2, iNOS, and induced phosphorylation of Akt, IκB-α, NFκB, and ERK1/2 in RASFs. TNF-α-induced expression of these molecules was inhibited in a dose-dependent manner by pre-treatment with honokiol. The inhibitory effect of honokiol on NFκB-p65 activity was also confirmed by immunocytochemical analysis. In conclusion, honokiol is a potential inhibitor of TNF-α-induced expression of inflammatory factors in RASFs, which holds promise as a potential anti-inflammatory drug.
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Xueting
authors.initials: X
authors.lastname: Shao
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wu
authors.forename: Tingting
authors.initials: T
authors.lastname: Feng
authors.forename: Changzhong
authors.initials: C
authors.lastname: Jin
authors.forename: Meixin
authors.initials: M
authors.lastname: Fang
authors.forename: Nanping
authors.initials: N
authors.lastname: Wu
authors.forename: Hangping
authors.initials: H
authors.lastname: Yao
mesh_terms: D001713:Biphenyl Compounds / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D017705:Lignans / Q000494:pharmacology*; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001713:Biphenyl Compounds; D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D017705:Lignans; D014409:Tumor Necrosis Factor-alpha; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols