Mechanism of Fangji Fulingtang for Treating Acute Kidney Injury Induced by Ischemia-reperfusion Based on Network Pharmacology and Molecular Docking Verification
10.13422/j.cnki.syfjx.20220515
- VernacularTitle:基于网络药理学和分子对接探究防己茯苓汤治疗缺血再灌注急性肾损伤的作用机制
- Author:
Jun-xin HUANG
1
;
Bi-xia WANG
1
;
Han-bin ZOU
1
;
Qiu-xin WU
2
;
Xin YIN
3
;
Shu-ying HUANG
4
;
Jun-bin XIE
1
;
Qing-qi YANG
1
;
Zhi-yan GAO
5
;
Zheng-yu ZHANG
5
Author Information
1. The Second Clinical School,Guangzhou Medical University,Guangzhou 511436,China
2. KingMed School of Laboratory Medicine, Guangzhou Medical University,Guangzhou 511436,China
3. School of Pediatrics,Guangzhou Medical University,Guangzhou 511436,China
4. The Third Clinical School,Guangzhou Medical University,Guangzhou 511436,China
5. School of Basic Medical Sciences,Guangzhou Medical University,Guangzhou 511436,China
- Publication Type:Journal Article
- Keywords:
Fangji Fulingtang;
acute kidney injury;
network pharmacology;
molecular docking
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2022;28(8):175-182
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the mechanism of Fangji Fulingtang in the treatment of acute kidney injury （AKI） induced by ischemia-reperfusion based on network pharmacology and experimental verification. MethodActive components of Fangji Fulingtang were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and previous report and targets of these components were predicted by SwissTargetPrediction. The targets of AKI were searched from GeneCards， Online Mendelian Inheritance in Man （OMIM）， the database of gene-disease associations （DisGeNET）， and Therapeutic Target Database （TTD）. Protein-protein interaction （PPI） network was constructed by STRING. Metascape was used for Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of core targets. Cytoscape was employed to construct the "medicinal-active component-target-disease" network and “active component-target-pathway” network. AutoDock was applied for molecular docking. Finally， animal experiment was carried out to validate the mechanism of Fangji Fulingtang in treatment of AKI. ResultA total of 137 active components and 858 targets of Fangji Fulingtang， 1 294 targets of AKI， and 267 targets of Fangji Fulingtang in the treatment of AKI were screened out. Phosphoinositide-3-kinase regulatory subunit 1 （PIK3R1）， phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit alpha （PIK3CA）， proto-oncogene tyrosine protein kinase （SRC）， protein kinase B1 （Akt1）， and mitogen-activated protein kinase 3 （MAPK3） were the key anti-AKI targets of Fangji Fulingtang， which were involved in 1 609 GO terms， particularly cell response to lipids， membrane rafts， and protein kinase activity， and 140 KEGG pathways such as PI3K/Akt signaling pathway， chemokine signaling pathway， and Toll-like receptor signaling pathway. Molecular docking showed that the core active components had strong binding affinity to the key targets. The hematoxylin and eosin （HE） staining results indicated that Fangji Fulingtang can significantly improve the pathological state and the serological results suggested that the levels of serum creatinine （SCr） and blood urea nitrogen （BUN） were significantly reduced. ConclusionThis study clarified the mechanism of Fangji Fulingtang in the treatment of AKI and found that Fangji Fulingtang had the multi-component， multi-target， and multi-pathway characteristics in the treatment of AKI. The result lays a foundation for further study of its specific mechanism.
