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Lycium barbarum<\/em> (Goji Berry) extracts and its taurine component inhibit PPAR-\u03b3-dependent gene transcription in human retinal pigment epithelial cells: Possible implications for diabetic retinopathy treatment<\/span><\/p>\n<\/div>\n\n
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M.K.Song, N.K.Salam, Basil D.Roufogalis, T.H.W.Huang\u00a0<\/span><\/div>\nFaculty of Pharmacy, The University of Sydney, NSW 2006, Australia<\/span><\/div>\nReceived 17 May 2011, Accepted 20 July 2011, Available online 27 July 2011.<\/span><\/div>\n<\/div>\n<\/div>\n\n
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Abstract<\/strong><\/span><\/p>\n\n
The peroxisome proliferator activated receptor-\u03b3 (PPAR-\u03b3) is involved in the pathogenesis of diabetic retinopathy. Diabetic retinopathy is a preventable microvascular diabetic complication that damages human retinal pigment epithelial cells. Taurine is abundant in the fruit of Lycium barbarum<\/em> (Goji Berry), and is reportedly beneficial for diabetic retinopathy. However, the mechanism of its action is unknown. Hence, we have investigated the mechanism of action of an extract from L. barbarum<\/em> on a model of diabetic retinopathy, the retinal ARPE-19 cell line, and identified the receptor function of taurine, an active component of L. barbarum<\/em> (Goji Berry) extract, which is potentially responsible for the protective effect on diabetic retinopathy. We demonstrate for the first time that L. barbarum<\/em> extract and its taurine component dose-dependently enhance PPAR-\u03b3 luciferase activity in HEK293 cell line transfected with PPAR-\u03b3 reporter gene. This activity was significantly decreased by a selective PPAR-\u03b3 antagonist GW9662. Moreover, L. barbarum<\/em> extract and taurine dose-dependently enhanced the expression of PPAR-\u03b3 mRNA and protein. In an inflammation model where ARPE-19 cells were exposed to high glucose L. barbarum<\/em> extract and taurine down-regulated the mRNA of pro-inflammatory mediators encoding MMP-9, fibronectin and the protein expression of COX-2 and iNOS proteins. The predicted binding mode of taurine in the PPAR-\u03b3 ligand binding site mimics key electrostatic interactions seen with known PPAR-\u03b3 agonists. We conclude that PPAR-\u03b3 activation by L. barbarum<\/em> extract is associated with its taurine content and may explain at least in part its use in diabetic retinopathy progression.<\/span><\/p>\n<\/div>\n<\/div>\n