Anti-ocular-inflammatory Effects of Salvia hypoleuca Extract on Rat Endotoxin-Induced Uveitis

Abstract: Salvia hypoleuca is used in Iranian traditional medicine as an agent for treatment of some diseases and troubles. In this study, attention was focused on the antioxidant effect of Salvia hypoleuca. The aim of the present study was to determine the effects of Salvia hypoleuca extract on Endotoxin-Induced Uveitis (EIU) in rats. In addition, the endotoxin-induced expression of the inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 proteins was determined in a mouse macrophage cell line (RAW 264.7 ) treated with Salvia hypoleuca extract in vitro, to clarify the anti-inflammatory properties. EIU was induced in male Wistar rats by a footpad injection of lipopolysaccharide (LPS). Immediately after the LPS injection, 1, 10, or 100 mg extract or 10 mg prednisolone was injected intravenously. After 24 h, the aqueous humor was collected from both eyes, and the number of infiltrating cells, protein concentration, Nitric Oxide (NO), prostaglandin (PG)-E2, and TNF-alevels in the aqueous humor were determined. RAW 264.7 cells treated with various concentrations of extract were incubated with 10 :g/mL LPS for 24 h. Levels of NO, PGE2, and TNF-a were determined. The expression of iNOS and COX-2 proteins was analyzed by Western blot analysis. The number of inflammatory cells, the protein concentrations, and the levels of NO, PGE2, and TNF-ain the aqueous humor in the groups treated with Salvia hypoleuca were significantly decreased in a dose-dependent manner. In addition, the anti inflammatory effect of 100 mg Salvia hypoleuca was as strong as that of 10 mg prednisolone. The antiinflammatory action of Salvia hypoleuca was stronger than that of either quercetin or anthocyanin administered alone. Extract also suppressed LPS-induced iNOS and COX-2 protein expressions in RAW 264.7 cells in vitro in a dosedependent manner. The results suggest that Salvia hypoleuca has a dose-dependent anti-ocular inflammatory effect that is due to the direct blocking of the expression of the iNOS and COX-2 enzymes and leads to the suppression of the production of NO, PGE2, and TNF-a