Abstract
Uveitis, an intraocular inflammatory disease, occurs mostly in young people and can result in the loss of socioeconomic capabilities. Silibinin has been shown to exert anti-inflammatory effects in human retinal pigment epithelial (RPE) cells. The present study investigated the anti-inflammatory effect of silibinin pretreatment on endotoxin-induced uveitis (EIU) in rats and the mechanisms by which it exerts these effects. Uveitis was induced via injection of lipopolysaccharides (LPS) into Lewis rats. Twenty-four hours after the LPS injection, histological examination showed that silibinin decreased inflammatory cell infiltration in the anterior segment of the eyes of LPS-treated rats. Analyses of the aqueous humor showed that silibinin decreased cell infiltration, protein concentration, nitric oxide (NO), and prostaglandin (PG)-E2 production. Western blot analysis indicated that silibinin decreased the expression of inducible NO synthase (iNOS), cyclooxygenase (COX-2), and phosphorylated IkB in the iris-ciliary body (ICB). Immunohistochemistry showed that silibinin decreased intercellular adhesion molecule (ICAM-1) expression in the ICB. In addition, western blot analysis showed that silibinin attenuated the expression of iNOS, COX-2, ICAM-1, and nuclear p65 in LPS-treated RAW cells. In conclusion, silibinin pretreatment prevents EIU and the subsequent production of proinflammatory mediators and ICAM-1, at least in part, by blocking the NF-κB-dependent signaling pathway both in vivo and in vitro. These effects may contribute to the silibinin-mediated preventive effects on intraocular inflammatory diseases such as acute uveitis.