Sinomenine ameliorates rheumatoid arthritis in rodent models: a systematic review and meta-analysis of anti-inflammatory and joint-protective effects

Objective This systematic review and meta-analysis synthesize preclinical evidence to evaluate the therapeutic efficacy of sinomenine in rodent models of rheumatoid arthritis, and integrate current understanding of its potential mechanisms. This study aims to provide preclinical evidence and mechanistic insights to guide the clinical development of sinomenine for rheumatoid arthritis. Methods Through the systematic search of 4 English and 4 Chinese databases up to November 2025, qualified studies were identified, and a total of 38 animal studies were finally included. The quality of the literature was evaluated using the bias risk assessment tool of SYRCLE, and meta-analysis was conducted using Review Manager 5.4 and Stata 18. The main evaluation indicators included clinical joint manifestations (arthritis index, paw volume), anti-inflammatory indicators (TNF-α, IL-1β, IL-6, IL-10), and joint-protective indicators (Histological score, MMP-9, RANKL, OPG). Results The meta-analysis demonstrated that sinomenine significantly improved arthritis index and reduced paw volume. The anti-inflammatory results indicated that the levels of TNF-α, IL-1β, and IL-6 were significantly decreased, while the level of IL-10 was increased. Regarding joint protective indicators, sinomenine markedly lowered the histological score and MMP-9 levels, increased OPG levels, but showed no significant effect on RANKL levels. Subgroup analysis identified a differential dose-response, with high-dose sinomenine more consistently improving clinical and inflammatory outcomes, and the low-dose group showed relative advantages in modulating joint-protective indices. Short-term intervention demonstrated superior efficacy in reducing inflammation and providing joint protection. Intraperitoneal injection provided the most robust and reproducible efficacy profile. Sensitivity analysis showed robust results, while funnel plots revealed publication bias. Conclusion Sinomenine alleviates systemic inflammation conditions and joint damage in rheumatoid arthritis rodents through its dual mechanisms of anti-inflammatory (inhibiting pro-inflammatory factors and promoting anti-inflammatory factors) and joint-protective (inhibiting tissue degradation and regulating bone metabolism). However, the results should be interpreted with caution due to species differences and potential publication bias. Future high-quality clinical trials are needed to verify the clinical value of sinomenine. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251181300 , identifier PROSPERO 2025 CRD420251181300.