title: Extract of Polygonum cuspidatum Attenuates Diabetic Retinopathy by Inhibiting the High-Mobility Group Box-1 (HMGB1) Signaling Pathway in Streptozotocin-Induced Diabetic Rats.
abstract: High-mobility group box-1 (HMGB1) is a well-known pro-inflammatory cytokine. We aimed to investigate the effect of the ethanol extract of the root of P. cuspidatum (PCE) on retinal inflammation in diabetic retinopathy. PCE (100 or 350 mg/kg/day) was administered to diabetic rats for 16 weeks, and hyperglycemia and body weight loss developed in the diabetic rats. The retinal expression levels of HMGB1 and receptor for advanced glycation end products (RAGE) and the activity of nuclear factor-kappa B (NF-κB) in the retina were examined. Additionally, a chromatin immunoprecipitation assay was performed to analyze the binding of NF-κB binding to the RAGE promoter in the diabetic retinas. The levels of HMGB1 and RAGE expression, NF-κB activity, and NF-κB binding to the RAGE promoter were increased in the diabetic retinas. However, treatment with PCE ameliorated the increases in HMGB1 and RAGE expression, and NF-κB activity in the retina. In addition, in diabetic rats, retinal vascular permeability and the loosening of the tight junctions were inhibited by PCE. These findings suggest that PCE has a preventative effect against diabetes-induced vascular permeability by inhibiting HMGB1-RAGE-NF-κB activation in diabetic retinas. The oral administration of PCE may significantly help to suppress the development of diabetic retinopathy in patients with diabetes.
authors.affiliation: Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea. ssen4022@kiom.re.kr.
authors.forename: Eunjin
authors.initials: E
authors.lastname: Sohn
authors.affiliation: Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea. dvmhyun@kiom.re.kr.
authors.forename: Junghyun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea. chskim@kiom.re.kr.
authors.forename: Chan-Sik
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea. candykong@kiom.re.kr.
authors.forename: Yun Mi
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea. jskim@kiom.re.kr.
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001665:Binding Sites; D001786:Blood Glucose / Q000378:metabolism; D002199:Capillary Permeability; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D045468:Fallopia japonica / Q000737:chemistry*; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D011401:Promoter Regions, Genetic; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D013311:Streptozocin; D015430:Weight Gain
chemical_list: C000593874:Ager protein, rat; D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D016328:NF-kappa B; D010936:Plant Extracts; D000067759:Receptor for Advanced Glycation End Products; D013311:Streptozocin
keywords: diabetic retinopathy; high-mobility group box-1; nuclear factor-kappa B; receptor for advanced glycation end products