Network pharmacology-molecular docking analysis and experimental validation to explore the protective mechanism of Mongolian medi-cine Gaoyou on renal function
10.12092/j.issn.1009-2501.2024.09.002
- VernacularTitle:网络药理学-分子对接分析及实验验证蒙药高尤的肾功能保护作用机制
- Author:
Celimuge
1
;
Hudeligen
;
Liang XU
Author Information
1. 内蒙古民族大学蒙医药学院,通辽 028000,内蒙古
- Keywords:
mongolian medicine Gaoyou;
acute renal injury;
network pharmacology;
molecular docking;
mechanism of action
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2024;29(9):968-978
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To explore the protective mecha-nism of Mongolian medicine Gaoyou on renal func-tion through network pharmacology molecular docking and animal experiments.METHODS:The effective active components and targets of Gao you acting on acute kidney injury(AKI)and the related targets of AKI disease were obtained by using the relevant database of traditional Chinese medicine.The targets and components were mutually con-structed to act on the network,and the signal path-ways of drugs and diseases were enriched and ana-lyzed.And the molecular docking validation study was carried out on the pharmacodynamic compo-nents with high moderate value in the network and the core action target.On this basis,after establish-ing the rat model of acute renal injury and giving Gaoyou intervention,the contents of creatinine(CR),urea nitrogen(BUN)and tumor necrosis fac-tor-A(TNF-α),Kidney damage molecule-1(Kim-1),cystatin C(Cys-C),neutrophil gelatinase related lip-id transporter(NGAL)in serum of rats were detect-ed,and renal tissue sections were observed with HE staining to verify the protective effect of Mon-golian medicine Gaoyou on renal function of rats with acute renal injury.The predicted signal path-way was verified by Western blot.RESULTS:40 key targets were obtained by network pharmacology and molecular docking analysis.KEGG and go en-richment analysis were carried out on the key tar-gets.ALB,AKT1,VEGFA,IL-6,CASP3 and other key targets were predicted,and cancer signal pathway,TNF signal pathway,PI3K/AKT signal pathway and other key pathways were predicted.The results of molecular docking showed that the main active components of Gaoyou had good binding activity with related targets.The results of animal experi-ments showed that Gao you had a good protective effect on renal function,and Cr and BUN were sig-nificantly lower than those in the model group(P＜0.05).The content of TNF-α decreased significantly(P＜0.05).Kim-1,Cys-C and NGAL decreased signifi-cantly(P＜0.05).HE staining showed that Gao can obviously improve the pathological state of acute renal damage.The expression of AKT1,p-AKT1 and CASP3 in renal tissue of rats with acute renal injury increased(P＜0.05).Compared with the model group,the expression of AKT1,p-AKT1 and CASP3 in renal tissue of rats in Gaoyou group decreased significantly(P＜0.05).CONCLUSION:Gaoyou can protect the renal function of rats with renal injury through multiple pathways such as anti-inflamma-tory,antioxidant,antithrombotic,anti apoptotic and so on through the characteristics of multi-com-ponent,multi target.Intervention of PKA3/AKT sig-nal pathway and apoptosis factor may be one of its main mechanisms.
