Panax notoginseng,a traditional Chinese medicine,exerts beneficial effect on diabetic kidney disease(DKD),but its mechanism is not well clarified.In this study we investigated the effects of ginsenoside Rb1(Rb1),the main active ingredients of Panax notoginseng,in alleviating podocyte injury in diabetic nephropathy and the underlying mechanisms.In cultured mouse podocyte cells,Rb1(10 μM)significantly inhibited high glucose-induced cell apoptosis and mitochondrial injury.Furthermore,Rb1 treatment reversed high glucose-induced increases in Cyto c,Caspase 9 and mitochondrial regulatory protein NOX4,but did not affect the upregulated expression of aldose reductase(AR).Molecular docking analysis revealed that Rb1 could combine with AR and inhibited its activity.We compared the effects of Rb1 with eparestat,a known aldose reductase inhibitor,in high glucose-treated podocytes,and found that both alleviated high glucose-induced cell apoptosis and mitochondrial damage,and Rb1 was more effective in inhibiting apoptosis.In AR-overexpressing podocytes,Rb1(10 μM)inhibited AR-mediated ROS overproduction and protected against high glucose-induced mitochondrial injury.In streptozotocin-induced DKD mice,administration of Rb1(40mg·kg-1·d-1,ig,for 7 weeks)significantly mitigated diabetic-induced glomerular injuries,such as glomerular hypertrophy and mesangial matrix expansion,and reduced the expression of apoptotic proteins.Collectively,Rb1 combines with AR to alleviate high glucose-induced podocyte apoptosis and mitochondrial damage,and effectively mitigates the progression of diabetic kidney disease.

Jia-yi He;Quan Hong;Bi-xia Chen;Shao-yuan Cui;Ran Liu;Guang-yan Cai;Jiao Guo;Xiang-mei Chen

Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China;Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Institute of Chinese Medicine, Guangdong Pharmaceutical University;Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou 510006, China

中国药理学报（英文版）

[1]Jia-yi He;Quan Hong;Bi-xia Chen;Shao-yuan Cui;Ran Liu;Guang-yan Cai;Jiao Guo;Xiang-mei Chen-.Ginsenoside Rb1 alleviates diabetic kidney podocyte injury by inhibiting aldose reductase activity)[J].中国药理学报（英文版）,2022(02):342-353

eparestat

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