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.
MeSH terms
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Animals
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Anterior Eye Segment / drug effects
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Anterior Eye Segment / metabolism
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Anterior Eye Segment / pathology
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Antioxidants / pharmacology
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Aqueous Humor / cytology
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Aqueous Humor / drug effects
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Aqueous Humor / metabolism
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Cyclooxygenase 2 / metabolism
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Dinoprostone / metabolism
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Disease Models, Animal
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In Vitro Techniques
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Inflammation Mediators / metabolism
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Intercellular Adhesion Molecule-1 / metabolism
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Lipopolysaccharides / toxicity
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Macrophage Activation / drug effects
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Male
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Mice
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NF-kappa B / metabolism
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Nitric Oxide / metabolism
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Nitric Oxide Synthase Type II / metabolism
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RAW 264.7 Cells
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Rats
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Rats, Inbred Lew
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Signal Transduction / drug effects
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Silybin
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Silymarin / pharmacology*
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Uveitis / chemically induced
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Uveitis / metabolism
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Uveitis / prevention & control*
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Antioxidants
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Inflammation Mediators
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Lipopolysaccharides
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NF-kappa B
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Silymarin
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Intercellular Adhesion Molecule-1
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Nitric Oxide
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Silybin
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Nitric Oxide Synthase Type II
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Nos2 protein, rat
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Cyclooxygenase 2
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Ptgs2 protein, rat
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Dinoprostone
Grants and funding
This work was supported by National Science Council, NSC102-2314-B-016-046-MY3 (Jiann-Torng Chen); National Science Council, NSC-102-2314-B-016-047 (Ching-Long Chen); Ministry of Science and Technology, Taiwan, MOST103-2314-B-016-015 (Ching-Long Chen); Ministry of Science and Technology, Taiwan, MOST 104-2314-B-016-035 (Yi-Hao Chen), Ministry of Science and Technology, Taiwan, MOST 105-2314-B-016-045 (Jiann-Torng Chen); and Tri-Service General Hospital, TSGH-C102-097 (Ching-Long Chen). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.