Title:Predicting the Pharmacological Targets of Astragalus membranaceus against Hypertensive Nephropathy
Volume: 21
Issue: 16
Author(s): Ningxin Zhang, Chen Guan, Lingyu Xu, Zengying Liu, Chenyu Li, Quandong Bu, Xuefei Shen and Yan Xu*
Affiliation:
- Department of Nephrology, the Affiliated Hospital of Qingdao University, Qingdao, China
Keywords:
Hypertensive nephropathy, Astragalus membranaceus, network pharmacology, molecular docking, quercetin, kaempferol.
Abstract:
Objective: Hypertension is one of the main causes of chronic kidney disease. Astragalus
membranaceus (AM), an important traditional Chinese medicine for treating hypertensive nephropathy,
has a complex composition that makes it challenging to explore its mechanism of action and
limits its clinical application. This study aims to investigate the underlying mechanism of AM in
treating hypertensive nephropathy.
Methods: We retrieved all the compound data of AM from the Traditional Chinese Medicine Systems
Pharmacology database and screened out the active compounds and their target proteins. Then,
a network of candidate compounds and target compounds of AM was constructed using Cytoscape
software. Furthermore, hypertensive nephropathy-related genes from the DisGeNET and GeneCards
databases were intersected with AM target proteins and hypertensive nephropathy-related genes to
determine the potential targets of AM in treating hypertensive nephropathy. Finally, after performing
Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment
analyses, we conducted molecular docking to verify the interaction between the main active ingredients
of AM and the core targets.
Results: A total of 87 effective components of AM were obtained from the Traditional Chinese Medicine
Systems Pharmacology (TCMSP) database. According to the network of active compounds and
their target proteins, 18 of the 20 effective compounds in AM could act on 210 proteins. Taking the
intersection of 274 hypertensive nephropathy-related genes and AM target proteins, 49 potential
targets of AM in treating hypertensive nephropathy were identified. Using the median degree value,
we determined 25 core targets of AM in treating hypertensive nephropathy. GO enrichment analysis
showed that the biological processes of AM on hypertensive nephropathy mainly focused on the
inflammatory response, hypoxia response, angiogenesis, cell proliferation, and cell migration. KEGG
pathway enrichment analysis mainly involved cancer pathways, the AGE-RAGE signaling pathway
in diabetic complications, blood flow shear stress, and atherosclerosis. Molecular docking results
showed that quercetin, kaempferol, and 7-O-methylisomucronulatol had strong binding activity with
several target proteins and may exert protective effects by stabilizing the interaction between molecules
through the intermolecular forces of hydrogen bonds.
Conclusion: This study reveals the targets of AM in treating hypertensive nephropathy using network
pharmacology and molecular docking, providing new clues for developing novel drugs for
hypertensive nephropathy and basic research development.
