title: Inhibitory effects of honokiol on lipopolysaccharide-induced cellular responses and signaling events in human renal mesangial cells.
abstract: Honokiol has been shown to possess a lot of pharmacologic benefits, including antioxidative, antiangiogenic and antineoplastic effects. In the present study, we investigated the anti-inflammatory effects of honokiol and the signaling mechanisms involved in lipopolysaccharide (LPS)-induced conditions in human renal mesangial cells (HRMCs). Honokiol did not significantly change HRMC viability when used at a concentration of <20 μmol/l but markedly altered cell viability at concentrations of >40 μmol/l. In this study, LPS treatment led to a marked upregulation of the levels of IL-1β, IL-18, TNF-α, TGF-β1, CCL2, CCL3, and CCL5 in HRMCs. The expression of COX-2, iNOS, and their products PGE(2) and NO also increased. The upregulation of these molecules was significantly abolished by honokiol in a dose-dependent manner. Moreover, honokiol almost completely reversed IL-1β, CCL3, and NO expression at 10 μmol/l, and IL-18, TNF-α, TGF-β1, and COX-2 expression at 20 μmol/l. In addition, phospho-NF-κB p65 at Ser536, phospho-Akt, and phospho-p42/44 were dramatically suppressed by honokiol in LPS-treated HRMCs. These results indicate that honokiol can inhibit the LPS-induced expression of inflammatory cytokines and mediators in HRMCs. The anti-inflammatory mechanisms of honokiol are partly due to the suppression of the phospho-NF-κB p65, phospho-Akt and phospho-p42/44 pathways.
authors.affiliation: Department of Endocrinology, Affiliated Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Fenping
authors.initials: F
authors.lastname: Zheng
authors.forename: Xueting
authors.initials: X
authors.lastname: Shao
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Zhou
authors.forename: Hong
authors.initials: H
authors.lastname: Li
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D017705:Lignans / Q000008:administration & dosage / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity; D050527:Mesangial Cells / Q000187:drug effects* / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D051546:Cyclooxygenase 2; D016207:Cytokines; D018836:Inflammation Mediators; D017705:Lignans; D008070:Lipopolysaccharides; D052247:Nitric Oxide Synthase Type II; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols