Inhibiting effect of Radix Hedysari Polysaccharide (HPS) on endotoxin-induced uveitis in rats

Purpose: The aim of this study is to investigate the anti-inflammatory effect of Radix Hedysari Polysaccharide (HPS) on clinical indicators, the expression of Toll-like receptor-4 (TLR4) and its downstream transduction molecules during endotoxin-induced uveitis in rats. Methods: EIU was induced through the intraperitoneal injection of male Wistar rats with lipopolysaccharide (LPS 200 mu g). HPS (400 mg/kg), DXM (1 mg/kg) or an equivalent volume of normal saline was injected intraperitoneally 1 h before the LPS induction. The clinical manifestation was observed and scored at 2-h intervals using a slit microscope. The degree of inflammatory reaction was determined by routine histological examinations, and the expression of TLR4 and MyD88 in the iris-ciliary body complex was detected through a double-labeled immunofluorescence study. Real-time RT-PCR was used to assess the effects of HPS on the expression of the TLR4 complex, MyD88 and NF-kappa B p65 mRNA. The protein expression levels of TLR4, MyD88 and NF-kappa B p65 were examined by western blot. Results: HPS treatment produced similar therapeutic results with dexamethasone by significantly reducing the clinical severity of EIU as well as fibrin exudations and inflammatory cell infiltration in the eye. Correspondingly, according to the immunofluorescence results, HPS treatment significantly suppressed the expression of TLR4 and MyD88 in the iris-ciliary body complex. HPS treatment could also remarkably reduce the mRNA and protein expression of the TLR4 complex, MyD88 and NF-kappa B p65. Conclusion: HPS can suppress the intraocular inflammation observed in EIU by inhibiting TLR4 and its downstream signal transduction pathway. (C) 2014 Elsevier B.V. All rights reserved.