Diosgenin, a steroidal sapogenin, arrests arthritis through modulation of inflammatory cytokines and oxidative stress biomarkers in Wistar rats.

Abstract

Diosgenin (DGN) is a well-known steroidal sapogenin that is obtained from the hydrolysis of dioscin. The current research aimed to explore the anti-inflammatory and anti-arthritic potential of DGN alone and in combination with methotrexate (MTX). The in-vitro antioxidant, and anti-arthritic potential was assessed by protein denaturation and Human red blood cell membrane stabilization assays. The in-vivo anti-inflammatory effect was examined by carrageenan-induced paw edema and xylene-induced ear edema methods. The arthritis was induced in Wistar rats by inoculation of 0.1ml Complete Freund's adjuvant in the left hind paw at day 1. The arthritic animals received MTX 1mg/kg as standard, DGN at 5, 10, 20mg/kg, and a combination treatment (DGN 20mg/kg + MTX) was administered orally from 8 to 28th day while normal and disease control received normal saline. DGN at 1600μg/ml exhibited the highest in-vitro activities in contrast to other tested concentrations. DGN at 20mg/kg exhibited the maximum (p < 0.05-0.0001) inhibition of inflammation in carrageenan and xyleneinduced edema models. Treatment with DGN and MTX alone and in combination significantly reduced the paw diameter, body weight, arthritic index, and pain. It restored altered blood parameters and oxidative stress biomarkers in contrast to the diseased control rats. DGN profoundly (P < 0.0001) downregulated mRNA expression of TNF-α, IL-1β, NF-ĸβ, and COX-2 while upregulated IL-4 and -10 in treated rats. The combination of DGN with MTX showed the highest therapeutic efficacy than individual therapy, so it can be used as an adjunct for rheumatoid arthritis treatment.