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

Abstract

Abstract Aims This research aimed to use a rat model of CFA-induced arthritis to evaluate the antiarthritic effects of Campesterol, a phytosterol with therapeutic promise for inflammatory ailments. Methodology : A total of 30 Sprague-Dawley rats, with weight range 250–350 g, were randomly split into five groups (n = 6). Injection of CFA on Day 0 induced arthritis, and therapy began on Day 8 and continued until Day 28. The severity of paw edema and arthritic symptoms were measured on Days 7th, 14th, 21st, and 28th. Blood was drawn after the sacrifice, and further tests included, X ray interpretation, haematological parameters, biochemical paramters, histopathological parameter, and inflammatory biomarkers were evaluated that found to be significantly reduced. Moreover mRNA expression levels of TNF-α, IL-1β, IL-6, NF-κB, MMP 3, COX I, COX II, and IL-4 were assesed by real time polymerase chain reaction and PGE2 level was also evaluated by enzyme-linked immunosorbent assay. Results The use of Campesterol significantly inhibited the progression of paw edema, culminating in a notable decrease in arthritic scor. Notably, campesterol treatment improved histopathological indicators overall. The mRNA expression levels of pro-inflammatory biomarkers such as TNF-α, NF-kB, IL-6, COX II, and IL-1β were decreased while IL-4 level was increased in treated groups as compared to arthritic control group. Moreover, treatment with campesterol and piroxicam significantly reduced PGE2 level. Haemoglobin, Red blood cells, white blood cells, and platelet counts were almost restored in the treated groups. Other indicators such as total bilirubin, creatinine, urea, alanine aminotransferase, alkaline phosphatase, and rheumatoid factor were found statistically insignificant. Conclusion Campesterol significantly possess significant antiarthritic and immunomodulatory properties by downregulating the mRNA expression levels of pro-inflammatory biomarkers such as TNF-α, NF-kB, IL-6, COX II, and IL-1β and upregulating the IL-4 level.