Mechanism of Yuquan Capsule in Treating Diabetic Nephropathy Based on Network Pharmacology and Experimental Valida-tion
10.16466/j.issn1005-5509.2024.10.003
- VernacularTitle:基于网络药理学和实验验证探讨玉泉胶囊治疗糖尿病肾病的作用机制
- Author:
Siying GAO
1
;
Fei LUO
;
Junfeng LI
Author Information
1. 浙江中医药大学基础医学院 杭州 310053
- Keywords:
Yuquan Capsule;
diabetic nephropathy;
network pharmacology;
molecular docking;
target prediction;
oxidative stress;
experimental validation;
mechanism of action
- From:
Journal of Zhejiang Chinese Medical University
2024;48(10):1209-1223
- CountryChina
- Language:Chinese
-
Abstract:
[Objective]To investigate the potential mechanism of Yuquan Capsule in treating diabetic nephropathy(DN)by network pharmacology and in vitro experiments.[Methods]The active ingredients and disease-associated genes of Yuquan Capsule were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Traditional Chinese Medicine Integrated Database(TCMID),the target genes of DN were screened by Genome Annotation Database Platform(GeneCards),Disease Gene Network(DisGeNET)database and Therapeutic Target Database(TTD).The protein-protein interaction(PPI)network was drawn by STRING 11.5 database,and visualized by Cytoscape 3.7.2 software.The key compounds and core targets were screened by CytoHubba and MCODE plugins of Cytoscape 3.7.2 software.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed by R software(ClusterProfiler package),and the molecular docking validation was performed by AutoDock and PyMOL software.[Results]There were 177 Yuquan Capsule against DN,477 active components and 135 targets of Yuquan Capsule against DN.The core targets included serine/threonine kinase 1(AKT1),interleukin-1 beta(IL1B),catalase(CAT),nitric oxide synthase 3(NOS3),leptin(LEP),insulin-like growth factor 1(IGF1)and C-C motif chemokine ligand 2(CCL2).GO enrichment analysis showed 2 557 related items,including 1 415 biological processes,657 cellular components and 48 molecular functions.KEGG pathway analysis showed that the targets of Yuquan Capsule against DN were enriched in 66 pathways,of which cyclic adenosine monophosphate(cAMP)signaling pathway and advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway in diabetic complications may be the key pathways of Yuquan Capsule in the treatment of DN.Molecular docking results showed that the core target and key compounds could bind well.Experimental verification showed that the protein level of CCL2 decreased in a drugdose-dependent manner,and the protein level of CAT and endothelial nitric oxide synthase(eNOs)increased in a drugdose-dependent manner.[Conclusion]Yuquan Capsule has the characteristics of multiple components and multiple targets in the treatment of DN.The mechanism may be related to the down-regulation of CCL2 and up-regulation of CAT and eNOs protein expression,inhibiting oxidative stress,and regulating the key pathway.
