title: Astragaloside IV, a novel antioxidant, prevents glucose-induced podocyte apoptosis in vitro and in vivo.
abstract: Glucose-induced reactive oxygen species (ROS) production initiates podocyte apoptosis, which represents a novel early mechanism leading to diabetic nephropathy (DN). Here, we tested the hypothesis that Astragaloside IV(AS-IV) exerts antioxidant and antiapoptotic effects on podocytes under diabetic conditions. Apoptosis, albuminuria, ROS generation, caspase-3 activity and cleavage, as well as Bax and Bcl-2 mRNA and protein expression were measured in vitro and in vivo. Cultured podocytes were exposed to high glucose (HG) with 50, 100 and 200 µg/ml of AS-IV for 24 h. AS-IV significantly attenuated HG-induced podocyte apoptosis and ROS production. This antiapoptotic effect was associated with restoration of Bax and Bcl-2 expression, as well as inhibition of caspase-3 activation and overexpression. In streptozotocin (STZ)-induced diabetic rats, severe hyperglycemia and albuminuria were developed. Increased apoptosis, Bax expression, caspase-3 activity and cleavage while decreased Bcl-2 expression were detected in diabetic rats. However, pretreatment with AS-IV (2.5, 5, 10 mg·kg(-1)·d(-1)) for 14 weeks ameliorated podocyte apoptosis, caspase-3 activation, renal histopathology, podocyte foot process effacement, albuminuria and oxidative stress. Expression of Bax and Bcl-2 mRNA and protein in kidney cortex was partially restored by AS-IV pretreatment. These findings suggested AS-IV, a novel antioxidant, to prevent Glucose-Induced podocyte apoptosis partly through restoring the balance of Bax and Bcl-2 expression and inhibiting caspase-3 activation.
authors: Department of Nephrology, Zhejiang Hospital, Hangzhou, China.
authors: Dingkun
authors: D
authors: Gui
authors: Yongping
authors: Y
authors: Guo
authors: Feng
authors: F
authors: Wang
authors: Wei
authors: W
authors: Liu
authors: Jianguo
authors: J
authors: Chen
authors: Yifang
authors: Y
authors: Chen
authors: Jianhua
authors: J
authors: Huang
authors: Niansong
authors: N
authors: Wang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D005947:Glucose / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D050199:Podocytes / Q000166:cytology* / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D012503:Saponins; D014315:Triterpenes; D051028:bcl-2-Associated X Protein; C052064:astragaloside A; D005947:Glucose