Anti-arthritic activity of agnuside mediated through the down-regulation of inflammatory mediators and cytokines

The purpose of this study was to elucidate the probable mechanism for the anti-arthritic activity of agnuside (AGN), a compound isolated from the leaf extract of Vitex negundo. The anti-inflammatory activity of AGN within a dose range of 1.56-12.50 mg/kg in normal and adrenalectomized rats was evaluated against different inflammagens. An array of pro-inflammatory mediators (PGE(2) and LTB4) and T-cell-mediated cytokines (IL-2, TNF-alpha, IFN-gamma, IL-4, IL-10, IL-17) was assayed using flow cytometry, in arthritic paw tissue homogenate and splenocytes of treated animals. Significant anti-arthritic activity was observed in the polyarthritis test in rats and this was associated with significant suppression of inflammatory mediators and T-cell-mediated cytokines (Th1/Th2). The anti-inflammatory activity in adrenalectomized rats confirmed that the effect of AGN is not mediated by the pituitary-adrenal axis. AGN also showed inhibition of vascular permeability and leukocyte migration in vivo. The study suggests the possible development of AGN as a therapeutic agent in the treatment of arthritis by the modulation of the host immune response.