Anti-arthritic effects of magnolol in human interleukin 1β-stimulated fibroblast-like synoviocytes and in a rat arthritis model

• Published in: PloS one 2012-02, Vol.7 (2), p.e31368-e31368
• Main Authors: Wang, Jyh-Horng, Shih, Kao-Shang, Liou, Jing-Ping, Wu, Yi-Wen, Chang, Anita Shin-Yuan, Wang, Kang-Li, Tsai, Ching-Lin, Yang, Chia-Ron
• Format: Article
• Language: English
• Subjects: Activation; Activator protein 1; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Arthritis; Arthritis - drug therapy; Arthritis - pathology; Bark; Biology; Biphenyl; Biphenyl Compounds - pharmacology; Biphenyl Compounds - therapeutic use; Bone surgery; Cell adhesion & migration; Chemistry; Cyclooxygenase-2; Cytokines; Cytokines - antagonists & inhibitors; Cytokines - blood; Deoxyribonucleic acid; Disease Models, Animal; DNA; Electrophoretic mobility; Enzyme-linked immunosorbent assay; Fibroblasts; Gene expression; Hospitals; Humans; Inflammation Mediators - antagonists & inhibitors; Inhibition; Interleukin; Interleukin 6; Interleukin-1beta - pharmacology; Kinases; Lignans - pharmacology; Lignans - therapeutic use; Lymphocytes; Matrix metalloproteinases; Matrix Metalloproteinases - drug effects; Medicine; Neutrophils; NF-κB protein; Nuclear transport; Orthopedics; Pathways; Pharmacy; Polymerase chain reaction; Prostaglandin E2; Proteins; Rats; Reporter gene; Rheumatoid arthritis; Rodents; Smooth muscle; Synovial Membrane - pathology; Synoviocytes; Transcription factors; Translocation; Treatment Outcome; Tumor necrosis factor-TNF; Western blotting
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0031368

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.