title: Anti-arthritic effects of magnolol in human interleukin 1β-stimulated fibroblast-like synoviocytes and in a rat arthritis model.
abstract: Fibroblast-like synoviocytes (FLS) play an important role in the pathologic processes of destructive arthritis by producing a number of catabolic cytokines and metalloproteinases (MMPs). The expression of these mediators is controlled at the transcriptional level. The purposes of this study were to evaluate the anti-arthritic effects of magnolol (5,5'-Diallyl-biphenyl-2,2'-diol), the major bioactive component of the bark of Magnolia officinalis, by examining its inhibitory effects on inflammatory mediator secretion and the NF-κB and AP-1 activation pathways and to investigate its therapeutic effects on the development of arthritis in a rat model. The in vitro anti-arthritic activity of magnolol was tested on interleukin (IL)-1β-stimulated FLS by measuring levels of IL-6, cyclooxygenase-2, prostaglandin E(2), and matrix metalloproteinases (MMPs) by ELISA and RT-PCR. Further studies on how magnolol inhibits IL-1β-stimulated cytokine expression were performed using Western blots, reporter gene assay, electrophoretic mobility shift assay, and confocal microscope analysis. The in vivo anti-arthritic effects of magnolol were evaluated in a Mycobacterium butyricum-induced arthritis model in rats. Magnolol markedly inhibited IL-1β (10 ng/mL)-induced cytokine expression in a concentration-dependent manner (2.5-25 µg/mL). In clarifying the mechanisms involved, magnolol was found to inhibit the IL-1β-induced activation of the IKK/IκB/NF-κB and MAPKs pathways by suppressing the nuclear translocation and DNA binding activity of both transcription factors. In the animal model, magnolol (100 mg/kg) significantly inhibited paw swelling and reduced serum cytokine levels. Our results demonstrate that magnolol inhibits the development of arthritis, suggesting that it might provide a new therapeutic approach to inflammatory arthritis diseases.
authors.affiliation: Department of Orthopedic Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jyh-Horng
authors.initials: JH
authors.lastname: Wang
authors.forename: Kao-Shang
authors.initials: KS
authors.lastname: Shih
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Liou
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Wu
authors.forename: Anita Shin-Yuan
authors.initials: AS
authors.lastname: Chang
authors.forename: Kang-Li
authors.initials: KL
authors.lastname: Wang
authors.forename: Ching-Lin
authors.initials: CL
authors.lastname: Tsai
authors.forename: Chia-Ron
authors.initials: CR
authors.lastname: Yang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy* / Q000473:pathology; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000097:blood; D004195:Disease Models, Animal; D005347:Fibroblasts; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D053583:Interleukin-1beta / Q000494:pharmacology; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D020782:Matrix Metalloproteinases / Q000187:drug effects; D051381:Rats; D013583:Synovial Membrane / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D017705:Lignans; C005498:magnolol; D020782:Matrix Metalloproteinases