Mechanistic Evaluation of Anti-Arthritic Effects of Campesterol Through Downregulation of TNF-α, IL-1β, IL-6, NF-κB, MMP 3,COX I and COX II and Upregulation of IL-4

Abstract

Aims: This study has been conducted to evaluate anti arthritic effects of compesterol, a phytosterol, which has been used to treat inflammatory disorders. Methodology: A study was conducted using the CFA-induced arthritic rat model to investigate campesterol's potential antiarthritic and anti-inflammatory effects. The study used thirty female rats, randomly divided into five groups, each containing six rats. CFA was injected on Day 0 to induce arthritis in the rats. Treatment with campesterol began on Day 8 and continued until Day 28. The arthritic score and paw edema volume were measured on Days 7, 14, 21, and 28. After the rats were sacrificed, blood samples were collected for further analysis. Different pro inflammatory mediators, histopathological parameters, X-Ray interpretation, biochemical parameters, q-PCR, and ELISA were also assessed . These assessments were likely used to investigate the potential mechanisms underlying the observed effects of campesterol on arthritis and inflammation in the rats. Results: Based on the results reported, treatment with campesterol appeared to have a positive effect on the arthritic rats. Specifically, the treatment inhibited the development of arthritis and decreased paw edema. The histopathological parameters evaluated were also significantly reduced, suggesting that the treatment may have positively affected the underlying pathology of arthritis. The qPCR analysis showed that treatment with campesterol significantly reduced pro-inflammatory cytokines TNF-a, NF- κB, IL-6, COX II, and IL-1 levels and potentiation of anti-inflammatory cytokine IL-4 levels. ELISA showed decreased levels of PGE2, a marker of inflammation, in all treated groups. The blood and biochemical parameters in the treated groups were nearly normalized, with restored levels of Hb and RBCs and reduced levels of WBCs. Platelets were also found to be normalized in treated groups. Significant differences were observed in the total bilirubin, creatinine, urea, ALT, AST, ALP, and rheumatoid factor between the treated and arthritic control groups, indicating that the treatment may have had a positive effect on these parameters as well. The results suggest that campesterol may have the potential as an antiarthritic and anti-inflammatory agent. Further studies could help elucidate its mechanisms of action and potential clinical applications. Conclusion: Paw edema reduced significantly compesterol, arthritic score as compared to diseased control group. Histopathologic, Haematological and biochemical parameters i.e. qPCR results showed supression of pro inflammmatory biomarkers such as TNF- α, NF-KB, IL-6, COX II and IL-1 and augmented levels of IL4 as compared to diseased control group. PGE 2 levels were found significantly reduced after treatment. This study validates immunomodulatory role of compesterol in rheumatoid arthritis. The compound had effects comparable with piroxicam.