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Effect of 20S-Protopanaxatriol on diabetic kidney disease
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DOI   10.11656/j.issn.1673-9043.2025.12.04
Key Words   diabetic kidney disease;20S-Protopanaxatriol;mass spectrometry imaging;pharmacodynamic evaluation
Author NameAffiliationE-mail
YU Lulu School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
YUAN Yu School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
LIU Xueke School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
QIN Xuebin School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
HUANG Liping School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
WANG Yuming School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China wangyuming226@163.com 
LI Yubo School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China yaowufenxi001@163.com 
Abstract
    [Objective] To explore the therapeutic effect of 20S-Protopanaxatriol(20S-PPT),an active substance in ginseng,on the occurrence and development of diabetic kidney disease(DKD). [Method] Using high glucose induced injury of human renal tubular epithelial cells(HK-2) to simulate an in vitro model of DKD. Set up control group,high glucose group,high glucose+20S-PPT group. After 48 hours of incubation,the potential therapeutic effect of 20S-PPT on DKD was preliminarily evaluated by detecting cell morphology,quantity,viability,apoptosis,mitochondrial function,and other indicators. Next,starting from the exploration of drug efficacy in animal models, a DKD mouse models were established and randomly divided into normal group,model group and 20S-PPT group. The 20S-PPT group obtained 20S-PPT by gavage and received treatment for 4 weeks. Subsequently,by observing and analyzing the general indicators of mice,detecting renal tissue pathological and biochemical indicators,oxidative stress indicators,and qualitatively and quantitatively evaluating the drug efficacy of 20S-PPT on mouse kidney injury. And explore the effect of 20S-PPT on metabolic disorders in the progression of DKD through mass spectrometry imaging technology. [Result] Compared with the control group,after 48 hours of treatment with high glucose(50 mmol/L),the morphology of HK-2 cells transformed from pebble shaped to fibrous,the number of cells decreased(P<0.01),the vitality decreased(P<0.01),the apoptosis rate and reactive oxygen species(ROS) level increased(P<0.05),and the mitochondrial membrane potential decreased;Compared with the high glucose group,the 20S-PPT(5 μmol/L) group showed a pebble shaped transformation in HK-2 cell morphology,a decrease in cell number and vitality(P<0.05),a decrease in cell apoptosis rate and ROS levels(P<0.05),and an increase in mitochondrial membrane potential after 48 hours of treatment. Compared with the control group,the fasting blood glucose,urinary albumin creatinine ratio,oral glucose tolerance,and renal index of the DKD model group mice were significantly increased(P<0.05). The levels of creatinine,urea nitrogen,uric acid,total cholesterol,triglycerides,low-density lipoprotein cholesterol,and malondialdehyde were significantly increased(P<0.05),while the levels of high-density lipoprotein cholesterol,superoxide dismutase,and glutathione peroxidase were significantly decreased(P<0.05). Compared with the DKD model group,the mice in the 20S-PPT(20 mg/kg) administration group showed significant reductions in fasting blood glucose,oral glucose tolerance,and renal index(P<0.05). The levels of creatinine, urea nitrogen,uric acid,total cholesterol,triglycerides,low-density lipoprotein cholesterol,and malondialdehyde were significantly reduced(P<0.05),while the levels of high-density lipoprotein cholesterol,superoxide dismutase,and glutathione peroxidase were significantly increased(P<0.05). In addition,20S-PPT can regulate various metabolic pathways in DKD mice,such as nucleotide metabolism, glucose and lipid metabolism,and tricarboxylic acid cycle. [Conclusion] In vitro studies have shown that 20S-PPT can improve HK-2 cell damage under high glucose conditions by regulating cell apoptosis,oxidative stress,and other effects at a concentration of 5 μmol/L after 48 hours of administration. Animal experiments further confirmed that 20S-PPT(20 mg/kg) can regulate renal function and pathological damage in DKD mice. Its specific mechanism of action is closely related to metabolic regulation.

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