Abstract
This study evaluated the impact of combining piperine and prednisolone on clinical symptoms and immune responses in Wistar rats with rheumatoid arthritis (RA) induced by Freund's complete adjuvant due to piperine known anti-inflammatory and immunomodulatory properties. The RA rats were randomly divided into five groups (n = 10): The RA rats were treated with phosphate-buffered saline, RA rats treated with piperine (100 mg kg(-1) orally), RA rats treated with prednisolone (10.00 mg kg(-1) orally), and RA rats treated with a combination of piperine and prednisolone (half doses of each orally). Treatment started on day five post-induction when all rats had a clinical score of ≥ 1. Disease symptoms were monitored every other day until day 23 post-induction. Combining the two medications at half doses led to a more significant reduction in disease severity, weight improvement, and histopathological changes compared to using each drug alone at the full doses. The combined treatment group exhibited the most favorable response in C-reactive protein, myeloperoxidase, and nitric oxide biochemical tests compared to the other treatment groups. The combined treatment group showed decreased expression of T-bet and RORɣt genes. However, there was no statistically significant difference in the expression of Foxp3 and GATA3 genes compared to the group receiving prednisolone alone. Overall, combining piperine with prednisolone may prove to be a beneficial approach for managing RA.