Sinomenine regulated gut-joint axis for alleviating rheumatoid arthritis.

BACKGROUND

Gut microbiota is considered as a new target for the treatment of rheumatoid arthritis (RA). However, the mechanism by which Sinomenine (SIN) alleviates RA by modulating gut microbiota has not been fully explored.

METHODS

The collagen-induced arthritis (CIA) rat model was established, and the therapeutic effect of SIN on CIA rats was evaluated. Alterations in gut microbiota and serum metabolites in CIA rats after SIN administration were assessed by 16S rRNA and non-targeted metabolomics methods. Then the CIA pseudo-sterile model was established by the combination of broad-spectrum antimicrobials (ATMs). The therapeutic effect, gut microbiota, and serum metabolites of SIN on CIA-ATM rats was investigated.

RESULTS

SIN significantly increased body weight, alleviated arthritis index, paw swelling, and ankle joint pathological changes, and reduced serum levels of pro-inflammatory cytokines interleukin (IL) -1beta, IL-6, IL-17 A, IL-18, and tumor necrosis factor (TNF)-alpha, and increased IL-10 in CIA rats in a dose-dependent manner. The composition of the gut microbiota was optimized after SIN was utilized. SIN regulated the serum metabolism of bile acids, glycerophospholipids, and fatty acids in CIA rats, thereby exerting anti-arthritis effects. In addition, SIN did not affect the arthritis-related indicators of CIA-ATM rats. Furthermore, SIN treatment did not significantly restore the diversity of gut microbiota in CIA-ATM rat. Meanwhile, SIN administration had no beneficial regulatory effect on the serum metabolome of CIA-ATM rats.

CONCLUSIONS

SIN exerts anti-arthritis effects, at least in part, by regulating the gut microbiota. Targeting the gut microbiota may be a future therapeutic strategy for RA management.