Pharmacological and Toxicological Study of Coumarinolignoids from Cleome viscosa in Small Animals for the Management of Rheumatoid Arthritis

Abstract

This study aims to explore the possible pharmacological potential of Cleome viscosa Linn (Cleomaceae), an annual weed, into therapeutic value-added products. In the present study, we have explored the pharmacological and toxicological profile of coumarinolignoids isolated from Cleome viscose for the management of rheumatoid arthritis and related complications in a small animal model. To avoid the biasness during experiments on animals, we have coded the isolated coumarinolignoids as CLIV-92 to perform the experimental pharmacological study. CLIV-92 was orally administrated (30,100, 300 mg/kg) to animal models of collagen-induced arthritis (CIA), carrageenan-induced acute inflammation, thermal and chemical-induced pain, and Brewerʼs yeast-induced pyrexia. Oral administration of CLIV-92 significantly decreases the arthritis index, arthritis score, and increases the limb withdrawal threshold in the CIA model in experimental rats. The anti-arthritis studies revealed that the anti-inflammatory effect of CLIV-92 was associated with inhibition of the production of inflammatory mediators like TNF-α, IL-6, IL-17A, MMP-1, MMP-9, Nitric oxide, and C-RP in CIA ratʼs serum, and also reduced the NFкB-p65 expression as evidence of immunohistochemistry in knee joint tissue of CIA rats, in a dose-dependent manner. Further individual experiments related to arthritis-related complications in experimental animals demonstrated the analgesic, anti-inflammatory, and antipyretic potential of CLIV-92 in a dose-dependent manner. Further, an in-vivo acute oral toxicity study concluded that CLIV-92 is safe in experimental animals up to 2,000 mg/kg dose. The results of this study suggested that the oral administration of CLIV-92 may be a therapeutic candidate for further investigation in the management of rheumatoid arthritis and related complications.

Dietary oleacein, a secoiridoid from extra virgin olive oil, prevents collagen-induced arthritis in mice

“…Our results are in agreement with those of previous studies and demonstrate that increased levels of Th-1 and Th-17 cytokines such as IL-1β, IL-6, IL-17, TNF-α, as well as MMP-3 and MMP-9 levels, were associated with disease onset and joint progression in CIA. 42 Though, arthritic mice fed with OLA-enriched diets showed a significant reduction in serum MMP-3 levels, as well as in IL-17, TNF- α, IL-1β and IL-6 pro-inflammatory cytokines in paw homogenates, also less immunostaining for MMP-9 in tarsal and metatarsal joints sections in comparison with CIA control group, correlating in parallel with the macroscopic and histological findings. Then, these data suggest that dietary OLA exerts anti-inflammatory effects through the modulated production of these key RA biomarkers.…”