title: Pretreatment with the total flavone glycosides of Flos Abelmoschus manihot and hyperoside prevents glomerular podocyte apoptosis in streptozotocin-induced diabetic nephropathy.
abstract: Diabetic nephropathy (DN) is an important diabetic complication, and podocyte apoptosis plays a critical role in the development of DN. In the present study, we examined the preventive effect of the total flavone glycosides of Flos Abelmoschus manihot (TFA) on urinary microalbumin and glomerular podocyte apoptosis in experimental DN rats. The preliminary oral administration of TFA (200 mg/kg/day) for 24 weeks significantly decreased the urinary microalbumin to creatinine ratio and 24-h urinary total protein in streptozotocin-induced DN rats. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay indicated glomerular cell apoptosis in DN rats was significantly improved by pretreatment with TFA. Furthermore, fluorescence-activated cell sorting and Hoechst 33342 staining suggested preincubation with hyperoside (50 and 200 μg/mL), the major active constituent of TFA, could significantly mitigate cultured podocyte apoptosis induced by the advanced glycation end-products (AGEs). Western blot analysis showed that increased caspase-3 and caspase-8 expressions induced by AGEs were also inhibited by pretreatment with hyperoside at both doses. Our results demonstrate that TFA pretreatment can decrease urinary albumin excretion in early-stage DN, which might be accomplished by preventing renal damage and podocyte apoptosis.
authors.affiliation: Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: An
authors.forename: Shi-Chao
authors.initials: SC
authors.lastname: Teng
authors.forename: Jing-Shun
authors.initials: JS
authors.lastname: Liu
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Shang
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Zhang
authors.forename: Yang-Gang
authors.initials: YG
authors.lastname: Yuan
authors.forename: Jiang-Yi
authors.initials: JY
authors.lastname: Yu
mesh_terms: D028483:Abelmoschus / Q000737:chemistry*; D000419:Albuminuria / Q000188:drug therapy / Q000652:urine; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors; D003404:Creatinine / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000652:urine; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D047309:Flavones / Q000494:pharmacology / Q000627:therapeutic use*; D035264:Flowers; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006027:Glycosides / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008517:Phytotherapy; D050199:Podocytes / Q000187:drug effects*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D061945:Caspase Inhibitors; D004365:Drugs, Chinese Herbal; D047309:Flavones; D017127:Glycation End Products, Advanced; D006027:Glycosides; C021304:hyperoside; D011794:Quercetin; D003404:Creatinine