title: Lycium barbarum (Goji Berry) extracts and its taurine component inhibit PPAR-γ-dependent gene transcription in human retinal pigment epithelial cells: Possible implications for diabetic retinopathy treatment.
abstract: The peroxisome proliferator activated receptor-γ (PPAR-γ) 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 (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 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 (Goji Berry) extract, which is potentially responsible for the protective effect on diabetic retinopathy. We demonstrate for the first time that L. barbarum extract and its taurine component dose-dependently enhance PPAR-γ luciferase activity in HEK293 cell line transfected with PPAR-γ reporter gene. This activity was significantly decreased by a selective PPAR-γ antagonist GW9662. Moreover, L. barbarum extract and taurine dose-dependently enhanced the expression of PPAR-γ mRNA and protein. In an inflammation model where ARPE-19 cells were exposed to high glucose L. barbarum 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-γ ligand binding site mimics key electrostatic interactions seen with known PPAR-γ agonists. We conclude that PPAR-γ activation by L. barbarum extract is associated with its taurine content and may explain at least in part its use in diabetic retinopathy progression.
authors.affiliation: Faculty of Pharmacy, The University of Sydney, NSW 2006, Australia.
authors.forename: M K
authors.initials: MK
authors.lastname: Song
authors.forename: N K
authors.initials: NK
authors.lastname: Salam
authors.forename: Basil D
authors.initials: BD
authors.lastname: Roufogalis
authors.forename: T H W
authors.initials: TH
authors.lastname: Huang
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000473:pathology; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D032305:Lycium / Q000737:chemistry*; D015394:Molecular Structure; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000187:drug effects; D013654:Taurine / Q000737:chemistry / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D047495:PPAR gamma; D010936:Plant Extracts; D012333:RNA, Messenger; D013654:Taurine; D005947:Glucose