BSS-4, a diosgenin analogue, reduces carrageenan-induced paw inflammation in rat

Inflammation is an adaptive response that ensures the survival of the organism in the face of injuries or trauma primarily via the immune system. However, overactivation of this process can be detrimental to the point of fatality. To overcome this overactivation, immunosuppressant agents such as steroids and non-steroidal anti-inflammatory drugs (NSAIDs) are used. Given the limitations of these drugs, including their side effects, an urgent need for development of potent and safer anti-inflammatory drugs is evident. Diosgenin, a steroidal saponin (a glycoside found in plants) and its analog, BSS-4 are gaining ground in this respect. Our objective in this study was to determine the effectiveness of BSS-4 in an established model of inflammation and provide clues on its mechanism of action. Carrageenan (Carr)-induced paw edema was used to evaluate the effectiveness of two doses of BSS-4 (0.5 and 1 mg/kg administered intraperitoneally) in adult male Wistar rats. Plantar edema was induced by subcutaneous injection of 50 µL of carrageenan (1 %) into the plantar aponeurosis of the right paw. Inflammatory cytokine markers, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) were quantified in this paw region using immunohistochemical assays. BSS-4 at 0.5 mg/kg dose, significantly reduced the paw edema up to three hours after administration. Concomitantly, TNF-α and IL-1β immunostaining were significantly reduced. BSS-4 also preserved the tissue architecture as assessed by hematoxylin and eosin (H&E) staining. These results indicate that BSS-4 can impart potent anti-inflammatory effects as well as reductions in TNF-α and IL-1β in an inflammatory rat model.