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N. M. Kalariya, S. Mohammad, A. B. M. Reddy, F. J. G. M. van Kuijk, K. V. Ramana; Plant Sterol Guggulsterone Prevents Endotoxin-Induced Uveitis in Rats. Invest. Ophthalmol. Vis. Sci. 2010;51(13):830.
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To investigate the anti-inflammatory effects of a plant sterol, guggulsterone, in endotoxin-induced uveitis (EIU) in rat model and to elucidate the underlying molecular mechanisms by which guggulsterone prevents ocular inflammation.
EIU was induced in Lewis rats by subcutaneous injection of lipopolysaccharide (LPS) (150 ug) treated without or with guggulsterone (30 mg/kg body wt, i.p) or its carrier. After 24 h, the rats were sacrificed and the eyes were enucleated, aqueous humors (AqH) were collected. The number of infiltrating cells, levels of metrixmetalloprotease-2 (MMP-2), nitric oxide (NO), and prostaglandin E2 (PGE2) were determined in AqH by specific ELISAs. Expressions of various inflammatory cytokines in AqH were determined by antibody array. Immunohistochemical analysis was performed to determine the expression of MMP-2, iNOS, Cox-2, phospho-IB and phospho-NF-B in the eye sections. Human primary non-pigment ciliary epithelial cells (HNPCECs) were used to determine the in vitro efficacy of guggulsterone on LPS-induced inflammatory signals.
Compared to controls, the EIU rat eyes AqH had significantly higher number of infiltrating cells, total protein, and inflammatory markers such as MMP-2, NO, and PGE2 and treatment of guggulsterone significantly prevented endotoxin-induced uveitis symptoms. Further, guggulsterone also prevented the expression of MMP-2, iNOS, and Cox-2 proteins as well as IB and NF-B in various eye tissues. Moreover, in incubation of HNPCECs with guggulsterone inhibited LPS-induced expression of inflammatory cytokines and chemokines.
Our results demonstrate that the plant sterol guggulsterone suppresses the ocular inflammation in rats suggesting that supplementation of guggulsterone could prevent ocular inflammation.
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