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Network Pharmacology and Experimental Validation to Explore That Celastrol Targeting PTEN is the Potential Mechanism of Tripterygium wilfordii (Lév.) Hutch Against IgA Nephropathy

Authors :
Zhao,Juanyong
Liu,Haiyang
Xia,Ming
Chen,Qian
Wan,Lili
Leng,Bin
Tang,Chengyuan
Chen,Guochun
Liu,Yu
Zhang,Lei
Liu,Hong
Zhao,Juanyong
Liu,Haiyang
Xia,Ming
Chen,Qian
Wan,Lili
Leng,Bin
Tang,Chengyuan
Chen,Guochun
Liu,Yu
Zhang,Lei
Liu,Hong
Publication Year :
2023

Abstract

Juanyong Zhao, Haiyang Liu, Ming Xia, Qian Chen, Lili Wan, Bin Leng, Chengyuan Tang, Guochun Chen, Yu Liu, Lei Zhang, Hong Liu Hunan Key Laboratory of Kidney Disease and Blood Purification, Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Hong Liu; Lei Zhang, Hunan Key Laboratory of Kidney Disease and Blood Purification, Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China, Tel +86-13973116951 ; +86-18673174522, Email liuhong618@csu.edu.cn; zhanglei_xp@163.comPurpose: Accumulating clinical evidence showed that Tripterygium hypoglaucum (Lév.) Hutch (THH) is effective against IgA nephropathy (IgAN), but the mechanism is still unclear. This study is to evaluate the renal protective effect and molecular mechanism of THH against IgAN via network pharmacology, molecular docking strategy and experimental validation.Methods: Several databases were used for obtaining the active ingredients of THH, the corresponding targets, as well as the IgAN-related genes. The critical active ingredients, functional pathways, and potential for the combination of the hub genes and their corresponding active components were determined through bioinformatics analysis and molecular docking. The IgAN mouse model was treated with celastrol (1 mg/kg/d) for 21 days, and the aggregated IgA1-induced human mesangial cell (HMC) was treated with various concentrations of celastrol (25, 50 or 75 nM) for 48 h. The immunohistochemistry and Western blot techniques were applied to evaluate the protein expression of the predicted target. The cell counting kit 8 (CCK8) was used to detect HMC proliferation.Results: A total of 17 active ingredients from THH were screened, covering 165 IgAN-related targets. The PPI network identified ten hub targets, including PTEN. The binding affinity between the celastrol and PTEN was the highest (− 8.69 kJ/mol). The immun

Details

Database :
OAIster
Notes :
text/html, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1379074239
Document Type :
Electronic Resource