title: Silibinin treatment prevents endotoxin-induced uveitis in rats in vivo and in vitro.
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.
authors.affiliation: Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan.|Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ching-Long
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan.|Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Jiann-Torng
authors.initials: JT
authors.lastname: Chen
authors.affiliation: Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan.|Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Liang
authors.affiliation: Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Tai
authors.affiliation: Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan.|Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Da-Wen
authors.initials: DW
authors.lastname: Lu
authors.affiliation: Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan.|Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yi-Hao
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000818:Animals; D000869:Anterior Eye Segment / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001082:Aqueous Humor / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D000067996:RAW 264.7 Cells; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction / Q000187:drug effects; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D014605:Uveitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012838:Silymarin; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D000077385:Silybin; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D015232:Dinoprostone