Sinomenine exerts anti-arthritis effects, at least in part, by regulating the gut microbiota, as demonstrated by loss of efficacy in pseudo-sterile CIA rats treated with broad-spectrum antimicrobials.
Key Findings
Results
Sinomenine significantly improved clinical measures of arthritis in CIA rats in a dose-dependent manner.
SIN treatment significantly increased body weight in CIA rats
SIN alleviated arthritis index and paw swelling in a dose-dependent manner
SIN reduced ankle joint pathological changes as assessed histologically
Effects were observed across multiple doses, indicating dose-dependency
Results
Sinomenine reduced pro-inflammatory cytokines and increased anti-inflammatory cytokine IL-10 in CIA rats.
SIN reduced serum levels of IL-1β, IL-6, IL-17A, IL-18, and TNF-α
SIN increased serum levels of IL-10
These cytokine changes occurred in a dose-dependent manner
Cytokine modulation was assessed in serum samples from CIA rats
Results
Sinomenine optimized the composition of gut microbiota in CIA rats.
Gut microbiota composition was assessed using 16S rRNA sequencing
SIN administration resulted in optimization of gut microbiota composition in CIA rats
Changes in microbiota were evaluated in the context of CIA-induced dysbiosis
Results
Sinomenine regulated serum metabolism of bile acids, glycerophospholipids, and fatty acids in CIA rats.
Non-targeted metabolomics methods were used to assess serum metabolites
SIN modulated bile acid, glycerophospholipid, and fatty acid metabolic pathways
These metabolic changes were associated with anti-arthritis effects
Serum metabolomic profiling was conducted in CIA rats following SIN administration
Results
Sinomenine did not affect arthritis-related indicators in pseudo-sterile CIA rats treated with broad-spectrum antimicrobials.
A CIA pseudo-sterile model was established using a combination of broad-spectrum antimicrobials (ATMs)
SIN administration had no effect on arthritis-related indicators in CIA-ATM rats
SIN did not significantly restore gut microbiota diversity in CIA-ATM rats
SIN had no beneficial regulatory effect on the serum metabolome of CIA-ATM rats
These findings demonstrate that the anti-arthritis effects of SIN are dependent on the presence of gut microbiota
Conclusions
The gut-joint axis is implicated as a key mechanism through which sinomenine alleviates rheumatoid arthritis.
SIN's anti-arthritis effects were lost when gut microbiota was depleted with antimicrobials
The authors concluded that SIN exerts anti-arthritis effects 'at least in part, by regulating the gut microbiota'
Targeting the gut microbiota was identified as a potential future therapeutic strategy for RA management
The study used both 16S rRNA sequencing and non-targeted metabolomics to characterize the gut-joint axis
Wang D, Ma J, Qiu Y, Gao H, Sun Z. (2026). Sinomenine regulated gut-joint axis for alleviating rheumatoid arthritis.. International immunopharmacology. https://doi.org/10.1016/j.intimp.2026.116460