Anti-inflammatory potential of carotenoid meso-zeaxanthin and its mode of action

Context: meso-Zeaxanthin (MZ) is a xanthophyll carotenoid with profound antioxidant activity. Objective: Oxidative stress plays a decisive role in numerous degenerative diseases including cancer. The present study evaluates anti-inflammatory effect of MZ. Materials and methods: Balb/c mice were treated with different doses of MZ (50 and 250 mg/kg b. wt, orally) 5 d before subcutaneous injection of carrageenan (1%), dextran (1%), and formalin (2%). Paw edema formation in MZ-treated and -untreated animals was measured using vernier calipers. Anti-inflammatory activity of MZ against lipopolysaccharide (LPS)-induced inflammatory model was studied by culturing macrophages in the presence and absence of LPS (5 mu g/ml) and different concentrations of MZ (5, 10, and 25 mu g/ml). After 24 h, the effect of MZ on pro-inflammatory cytokine levels in macrophages was analyzed by ELISA and its effect on various inflammatory genes was studied by RT-PCR. Results: MZ administration at different doses significantly (p<0.001) inhibited paw edema induced by carrageenan, dextran, and formalin in mice. MZ also exhibited profound anti-inflammatory effect against LPS-induced inflammation in macrophages. Increased production of nitric oxide, C-reactive proteins, and various pro-inflammatory cytokines (TNF-alpha, interleukin-1 beta, and interleukin-6) in LPS-stimulated macrophages was significantly reduced by MZ treatment. Moreover, LPS-stimulated up-regulated mRNA expression of various inflammatory mediator genes like COX-2, TNF-alpha, and iNOS was down-regulated by MZ administration. Discussion and conclusion: MZ has potent anti-inflammatory effect which can be due to its down-regulated expression of various inflammatory mediator genes. Since cancer is considered as an inflammatory disease, the present study points towards the importance of MZ in chemo-preventive strategy.