Investigating the therapeutic potential of sinomenine in rheumatoid arthritis: anti-inflammatory, antioxidant, and immunomodulatory mechanisms

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Abstract
An autoimmune disease, rheumatoid arthritis (RA) is characterized by the onset of inflammation and subsequent damage to the joints. Although several therapies are available for RA, none are effective, and many have undesirable side effects. The roots of Sinomenium acutum produce an alkaloid called Sinomenine (SIN), which has been used for centuries in Chinese medicine to treat arthritis due to its anti-inflammatory properties. This study aimed to explore the potential therapeutic benefits of SIN through oral administration following RA induction using Freund’s complete adjuvant (FCA) injections. The study monitored changes in the arthritic index, hind paw volume, inflammation and oxidative stress markers. Results demonstrated that SIN effectively inhibited the activity of NF-κB and IKKβ in knee joint tissues, which led to a decrease in tissue levels of TNF-α, IL-6, IL-1β, and iNOS in RA-induced rats. The production of anti-inflammatory cytokines such as IL-10, Arg-1, and Fizz1 also increased. In rat knee joints, SIN elevated the expression of TIMP-1 and TIMP-3 and decreased the expression of MMP-2 and MMP-9. Additionally, SIN modulated the RANK/RANKL/OPG pathway in RA-induced rat knee joint tissues, reducing RANKL expression and increasing OPG. SIN also effectively decreased MDA, NO, and elevated antioxidant enzymes (SOD, CAT, GPx, and GSH) in RA-induced rats via Nrf2/Keap 1 signaling pathway activation. In conclusion, this study suggests that SIN possesses potential therapeutic benefits for treating RA by modulating the RANK/RANKL/OPG pathway, which may impact osteoclast activity, oxidative stress, and inflammation in knee joint tissues.

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