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


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 μg/ml) and different concentrations of MZ (5, 10, and 25 μg/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-α, interleukin-1β, 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-α, and iNOS was down-regulated by MZ administration.


CONCLUSIONS
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.
Department of Biochemistry and.
A P
AP
Firdous
Girija
G
Kuttan
Ramadasan
R
Kuttan
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002338:Carotenoids / Q000494:pharmacology* / Q000627:therapeutic use; D004487:Edema / Q000188:drug therapy* / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D065146:Zeaxanthins / Q000494:pharmacology / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D065146:Zeaxanthins; D002338:Carotenoids; C584722:meso-zeaxanthin
Carrageenan; dextran; formalin; lipopolysaccharide; macrophages; pro-inflammatory cytokines