title: Puerarin inhibits the retinal pericyte apoptosis induced by advanced glycation end products in vitro and in vivo by inhibiting NADPH oxidase-related oxidative stress.
abstract: Retinal pericyte loss is one of the histopathological hallmarks of early diabetic retinopathy. Puerarin (4'-7-dihydroxy-8-beta-d-glucosylisoflavone), which is an isoflavone-C-glucoside, causes various pharmacological effects that include antihyperglycemic and anti-inflammatory activities. In the present study, we determined the efficacy and possible mechanism of puerarin on the advanced glycation end product (AGE)-modified bovine serum albumin (BSA)-induced apoptosis of cultured bovine retinal pericytes and rat retinal pericytes in intravitreally AGE-modified rat serum albumin (RSA)-injected eyes. Puerarin significantly inhibited pericyte apoptosis, the generation of reactive oxygen species (ROS), and NADPH oxidase activity by inhibiting the phosphorylation of p47phox and Rac1 which were induced by the AGE-BSA treatment. The puerarin treatment markedly suppressed the activation of nuclear factor-kappaB (NF-κB). In addition, the in vivo apoptosis of the retinal pericyte of rats that was stimulated by the intravitreal injection of AGE-RSA was evidently attenuated by the puerarin treatment. These results demonstrate that puerarin may exert inhibitory effects on AGE-induced pericyte apoptosis by interfering with the NADPH oxidase-related ROS pathways and blocking NF-κB activation, thereby ameliorating retinal microvascular dysfunction.
authors.affiliation: Traditional Korean Medicine Based Herbal Drug Research Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, 1672 Yuseongdaero, Yuseong-gu, Daejeon 305-811, South Korea. jskim@kiom.re.kr
authors.forename: Junghyun
authors.initials: J
authors.lastname: Kim
authors.forename: Ki Mo
authors.initials: KM
authors.lastname: Kim
authors.forename: Chan-Sik
authors.initials: CS
authors.lastname: Kim
authors.forename: Eunjin
authors.initials: E
authors.lastname: Sohn
authors.forename: Yun Mi
authors.initials: YM
authors.lastname: Lee
authors.forename: Kyuhyung
authors.initials: K
authors.lastname: Jo
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D058449:Intravitreal Injections; D007529:Isoflavones / Q000494:pharmacology / Q000627:therapeutic use*; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D020286:Pericytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D017127:Glycation End Products, Advanced; D007529:Isoflavones; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein; C033607:puerarin