Total saponins of Aralia taibaiensis protects myocardial cells against oxidative stress through the Nrf2-dependent antioxidant pathway
Background: Patients with type 2 diabetes have increased cardiovascular disease risk compared with those without diabetes.Hyperglycemia can induce reactive oxygen species (ROS) generation,which contributes to development of diabetic cardiomyopathy.Our previous study has demonstrated that total saponins of Aralia taibaiensis (sAT),a frequently-used antidiabetic in traditional Chinese medicine (TCM),can scavenge free radicals in vivo and have good antioxidant ability on lipid peroxidation of rat liver microsomes.To investigate whether sAT could protect the heart,while it was in the treatment of diabetes,we designed this study to elucidate cardioprotective effects of sAT.Methods and results: Oxidative stress was induced in H9c2 cells by high glucose (33 mM) and glucose oxidase (15mU) and the protective effects of sAT were evaluated.Treatment of H9c2 cells with G/GO resulted in an increase in cell death,intracellular ROS level and cell oxidative injury,which were markedly reduced by sAT treatment.Further study revealed that sAT induced the nuclear translocation of Nrf2,enhanced the expression of Nrf2-related antioxidant proteins heme oxygenase (HO-1) and NAD (P) H quinone oxidoreductase-1 (NQO-1).Inhibition of Nrf2 by siRNA reduced sAT-induced upregulation of these antioxidant genes.Western blotting and luciferase assay revealed sAT activated Nrf2 via the PI3K/Akt pathway.Moreover,Nrf2 siRNA markedly reduced the cytoprotective effects of sAT.Conclusions: sAT exerts cytoprotective effects against oxidative stress induced by hyperglycemia.This cardioprotection is mediated,at least in part,through PI3K/Akt/Nrf2 pathways,which further activates Nrf2-regulated antioxidant enzymes.sAT might be a promising candidate for the treatment of diabetic cardiomyopathy.
Type 2 diabetes Reactive oxygen species Antioxidant response element Total saponins of Aralia taibaiensis Nfr2 AKT
DUAN Jialin YAN Jiajia WU Xiaoxiao XI Miaomiao WEN Aidong CUI Jia GUAN Yue YIN Ying WEI Guo WENG Yan ZHU Yanrong GUO Chao WANG Yanhua
Department of pharmacy,Xijing hospital,The Fourth Military Medical University,Xi’an,Shanxi,710032
国内会议
南宁
英文
1-26
2013-11-01（万方平台首次上网日期，不代表论文的发表时间）