Mechanism of Astragalus Membranaceus in the Treatment of Diabetic Nephropathy Based on Network Pharmacology

Abstract

Background: Diabetic nephropathy (DN), which affects more than 40% of diabetic patients, is still the main cause of end-stage renal disease in most countries. Prescription containing Astragalus Membranaceus (AM) in the treatment of early stage DN with significant effect, but the mechanism is unclear, which we would explore based on network pharmacology.Method: First, we searched the database of China National Knowledge Internet, Wanfang Database, Chinese Biomedical Literature Database, PubMed, EMBASE, Cochrane database about the randomized, single (double) blind, controlled clinical studies of prescription containing AM in the treatment of DN, determined the effectiveness of prescription containing AM in the treatment of DN. Then, the effective components of AM in Traditional Chinese Medicine systems taxonomy database and analysis platform (TCMSP), Traditional Chinese medicine integrated database (TCMID) and Bioinformatics analysis tool for molecular mechanism of traditio Internal Chinese medicine (BATMAN-TCM) database were searched. According to the oral utilization ≥ 30% and drug-like ≥0.18, the effective components were screened. PubChem and health information technology (HIT) databases were searched for query validation targets and Simplified molecular input line entry specification (SMILES) of the effective ingredients, and Swisstarget prediction database was used to obtain prediction targets (possibility > 0). Drugbank, transient triple differential (TTD), and DisGeNET were searched for the targets related to DN. Finally, the data were integrated by the Cytoscape software, the drug-target-disease network was drawn, the protein interaction network was drawn with String database, and the signal pathway enrichment analysis was carried out with ClueGO.Result: The results showed that prescription containing AM could effectively reduce the urinary protein excretion rate [95% md-43.30 (- 57.00, - 29.61)]. 51 active components, 396 verified targets and 2330 predicted targets were searched. A total of 120 DN related targets were retrieved. 21 targets were found with Cytoscape. The main pathways were Interleukin-4 and 13 signaling, Activation of Matrix Metalloproteinases, EPH-Ephrin signaling.Conclusion: Prescription containing AM could effectively reduce the urinary protein excretion rate of DN patients. We speculated that AM mainly treated DN by regulating Angiotensin-converting enzyme (ACE), Vascular endothelial growth factor A (VEGFA), Janus Kinase 1 (JAK1), and interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling, activation of matrix metalloproteins, ephrin signaling and other signaling pathways based on network pharmacology, which would be verified by animal experiments or in vitro experiments in the later.