Alpha7 nAChR Expression Is Correlated with Arthritis Development and Inhibited by Sinomenine in Adjuvant-Induced Arthritic Rats

Sinomenine (SIN) is the active ingredient of the Chinese herb Sinomenium acutum that has been used to treat rheumatoid arthritis (RA) for about 30 years in China. Marked expression of the alpha7 nicotinic acetylcholine receptor (7nAChR) in the joint synovium of RA patients suggested a relationship between 7nAChR and RA. This study investigated the relationship between 7nAChR and RA development and the effects of SIN on 7nAChR expression in vivo and in vitro. Sprague-Dawley rats were injected with complete Freund's adjuvant to induce arthritis and then treated with SIN or methotrexate (MTX) from day 0 to day 30. Four clinical parameterspaw volume, arthritic index (AI), serum TNF- concentration, and erythrocyte sedimentation rate (ESR)were measured. Splenic lymphocytes were isolated for Bacille Calmette Guerin (BCG) stimulation. 7nAChR expression in tissues and cells was examined by RT-PCR, western blot, immunofluorescence, flow cytometry, and immunohistochemistry. Cell proliferation was evaluated by the CCK-8 assay. The relationship between 7nAChR expression and the four clinical parameters was analyzed by single-factor correlation analysis. Our results showed that the paw volume, AI, TNF- concentration, and ESR in adjuvant-induced arthritic (AIA) rats were reduced by SIN or MTX treatment. SIN decreased 7nAChR expression in tissues and cells compared to the model group, while MTX had no significant effect on 7nAChR expression. Moreover, there was a positive relationship between 7nAChR expression and paw swelling, AI, and TNF- concentration. Splenic lymphocyte activation was accompanied by increased 7nAChR expression, while SIN treatment inhibited cell activation and downregulated 7nAChR expression. 7nAChR expression showed a positive correlation with the progression of RA in AIA rats that may involve lymphocyte activation. Different from MTX, the inhibition of SIN on 7nAChR expression might contribute to its antiarthritic effect, suggesting that SIN could be an important supplement to the treatment strategy for RA.