JYH-HORNG WANGShih K.-S.Liou J.-P.Wu Y.-W.Chang A.S.-Y.Wang K.-L.Tsai C.-L.CHIA-RON YANG2020-02-102020-02-1020121932-6203https://www.scopus.com/inward/record.uri?eid=2-s2.0-84863171722&doi=10.1371%2fjournal.pone.0031368&partnerID=40&md5=a2ed74381eabbb6dd991d9ba9c8aaf4chttps://scholars.lib.ntu.edu.tw/handle/123456789/455892Fibroblast-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. ? 2012 Wang et al.[SDGs]SDG3[SDGs]SDG15collagenase 3; cyclooxygenase 2; I kappa B kinase beta; immunoglobulin enhancer binding protein; interleukin 6; interstitial collagenase; magnolol; mitogen activated protein kinase; prostaglandin E2; transcription factor AP 1; autacoid; biphenyl derivative; cytokine; interleukin 1beta; lignan; magnolol; matrix metalloproteinase; nonsteroid antiinflammatory agent; animal experiment; animal model; animal tissue; arthritis; article; binding affinity; cell stimulation; confocal microscopy; controlled study; DNA binding; drug mechanism; drug structure; enzyme inhibition; enzyme linked immunosorbent assay; female; gel mobility shift assay; human; human cell; in vitro study; in vivo study; nonhuman; protein blood level; protein expression; rat; reverse transcription polymerase chain reaction; signal transduction; Western blotting; animal; arthritis; blood; disease model; drug antagonism; drug effect; fibroblast; pathology; synovium; treatment outcome; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Biphenyl Compounds; Cytokines; Disease Models, Animal; Fibroblasts; Humans; Inflammation Mediators; Interleukin-1beta; Lignans; Matrix Metalloproteinases; Rats; Synovial Membrane; Treatment Outcomejournal article10.1371/journal.pone.0031368223595882-s2.0-84863171722