Phillyrin ameliorated collagen-induced arthritis through inhibition of NF-KB and MAPKs pathways in fibroblast-like synoviocytes

The discovery of alternative medicines with less adverse effects is extremely urgent for rheumatoid arthritis (RA). Phillyrin (Phil), the predominant lignan glycoside of Forsythia suspensa, has been reported to exert several pharmacological effects, such as antivirus, anti-inflammation, anti-oxidation, anti-obesity, and antipyretic activity. However, the effect of Phil on RA remains unknown. In this study, We utilized both in vivo collagen-induced arthritis (CIA) rat models and in vitro TNFa-induced fibroblast-like synoviocytes (FLSs) to study the inhibitory effects of Phil on RA. The in vivo studies revealed that Phil treatment effectively ameliorated synovial inflamma-tion and bone erosion in CIA rats. The in vitro studies demonstrated that Phil could significantly suppress the proliferation and migration of arthritic FLSs. In addition, treatment with Phil resulted in decreased mRNA expression of proinflammatory cytokines including TNFa, IL-1b, IL-6, IL-8 and MMP9. Molecular mechanistic investigations revealed that the suppressive effects of Phil were mediated by blockade of the MAPK (ERK, p38, and JNK) and NF-KB pathways. Taken together, our findings suggest that Phil has an anti-arthritic effect in CIA rats by inhibiting the pathogenic characteristic of arthritic FLSs throught suppression of NF-KB and MAPKs signaling pathways. These results demonstrate the potential of Phil as a novel therapeutic agent for the treatment of RA. (c) 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).