title: Corosolic acid inhibits the proliferation of glomerular mesangial cells and protects against diabetic renal damage.
abstract: Diabetic nephropathy (DN) is one of the major complications of diabetes mellitus (DM). This study aimed to explore the effects of corosolic acid (CA) on the renal damage of DM and the mechanisms behind these effects. The renoprotective effect of CA was investigated in type 1 diabetic rats and db/db mice. The kidneys and glomerular mesangial cells (GMCs) were used to study the proliferation of GMCs by immunostaining and MTT assay. Further immunoblotting, siRNA, qPCR analysis, and detecting of NADPH oxidase activity and reactive oxygen species (ROS) generation were performed to explore relevant molecular mechanisms. In CA-treated diabetic animals, diabetes-induced albuminuria, increased serum creatinine and blood urea nitrogen were significantly attenuated, and glomerular hypertrophy, mesangial expansion and fibrosis were ameliorated. Furthermore, CA significantly inhibited proliferation of GMCs and phosphorylation of ERK1/2 and p38 MAPK in both diabetic animals and high glucose (HG)-induced GMCs. CA also normalized Δψm and inhibited HG-induced NADPH oxidase activity, ROS generation and NOX4, NOX2, p22(phox) and p47(phox) expression. More importantly, CA inhibited GMC proliferation mediated by NADPH/ERK1/2 and p38 MAPK signaling pathways. These findings suggest that CA exert the protective effect on DN by anti-proliferation resulted from inhibition of p38 MAPK- and NADPH-mediated inactivation of ERK1/2.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiao-Qiang
authors.initials: XQ
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.|Cadet Brigade, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Tian
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Cadet Brigade, Fourth Military Medical University, Xi'an 710032, China.|Department of Natural Medicine &Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jun-Cheng
authors.initials: JC
authors.lastname: Huo
authors.affiliation: Department of Natural Medicine &Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Liu
authors.affiliation: Department of Natural Medicine &Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ming-Gao
authors.initials: MG
authors.lastname: Zhao
authors.affiliation: Department of Natural Medicine &Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014315:Triterpenes / Q000008:administration & dosage*
chemical_list: D001786:Blood Glucose; D017382:Reactive Oxygen Species; D014315:Triterpenes; C113861:corosolic acid; D019255:NADPH Oxidases