Network Pharmacology Combined with Bioinformatics to Investigate the Mechanisms and Molecular Targets of Astragalus Radix-Panax notoginseng Herb Pair on Treating Diabetic Nephropathy

Abstract

Background. Astragalus Radix (AR)-Panax notoginseng (PN), a classical herb pair, has shown significant effects in treating diabetic nephropathy (DN). However, the intrinsic mechanism of AR-PN treating DN is still unclear. This study aims to illustrate the mechanism and molecular targets of AR-PN treating DN based on network pharmacology combined with bioinformatics. Materials and Methods. The Traditional Chinese Medicine Systems Pharmacology database was used to screen bioactive ingredients of AR-PN. Subsequently, putative targets of bioactive ingredients were predicted utilizing the DrugBank database and converted into genes on UniProtKB database. DN-related targets were retrieved via analyzing published microarray data (GSE30528) from the Gene Expression Omnibus database. Protein-protein interaction networks of AR-PN putative targets and DN-related targets were established to identify candidate targets using Cytoscape 3.8.0. GO and KEGG enrichment analyses of candidate targets were reflected using a plugin ClueGO of Cytoscape. Molecular docking was performed using AutoDock Vina software, and the results were visualized by Pymol software. The diagnostic capacity of hub genes was verified by receiver operating characteristic (ROC) curves. Results. Twenty-two bioactive ingredients and 189 putative targets of AR-PN were obtained. Eight hundred and fifty differently expressed genes related to DN were screened. The PPI network showed that 115 candidate targets of AR-PN against DN were identified. GO and KEGG analyses revealed that candidate targets of AR-PN against DN were mainly involved in the apoptosis, oxidative stress, cell cycle, and inflammation response, regulating the PI3K-Akt signaling pathway, cell cycle, and MAPK signaling pathway. Moreover, MAPK1, AKT1, GSK3B, CDKN1A, TP53, RELA, MYC, GRB2, JUN, and EGFR were considered as the core potential therapeutic targets. Molecular docking demonstrated that these core targets had a great binding affinity with quercetin, kaempferol, isorhamnetin, and formononetin components. ROC curve analysis showed that AKT1, TP53, RELA, JUN, CDKN1A, and EGFR are effective in discriminating DN from controls. Conclusions. AR-PN against DN may exert its renoprotective effects via various bioactive chemicals and the related pharmacological pathways, involving multiple molecular targets, which may be a promising herb pair treating DN. Nevertheless, these results should be further validated by experimental evidence.

Combining network pharmacology with chromatographic fingerprinting and multicomponent quantitative analysis for the quality evaluation of Astragali Radix

“…In addition, MAPK1, AKT1, TP53, RELA and JUN were considered core potential therapeutic targets of AR for treating diabetic nephropathy. Molecular docking showed that these core targets had a good binding affinity to quercetin, kaempferol, isorhamnetin and formononetin (Zhao et al, 2021). Astragalosides have neuroprotective, anticancer and antidiabetic activities, which are related to the core targets of STAT3, JUN and TNF (Zhang et al, 2020).…”

“…In addition, MAPK1, AKT1, TP53, RELA and JUN were considered core potential therapeutic targets of AR for treating diabetic nephropathy. Molecular docking showed that these core targets had a good binding affinity to quercetin, kaempferol, isorhamnetin and formononetin (Zhao et al, 2021).…”

Oral Astragalus Root Supplementation for Mild to Moderate Chronic Kidney Disease: A Self-Controlled Case-Series

“…Previous studies have reported on the various bioactive chemicals in astragalus root ( Bratkov et al, 2016 ) and related pharmacological pathways involving molecular targets, including antioxidants, anti-inflammatory response, and antiapoptosis, and cell cycle regulation ( Zhao et al, 2021 ). Astragalus root is also effective in reducing fasting blood glucose and albuminuria levels, in reversing the glomerular hyperfiltration state, and in ameliorating the pathological changes of early diabetic nephropathy in animal models ( Zhang et al, 2009 ).…”

Exosomes: A novel insight into traditional Chinese medicine

“…Quercetin, a phenolic flavonol compound, can be extracted from multiple Chinese medicine herbs, including Mulberry leaves, Radix Bupleuri , licorice, Astragali Radix, and Panax notoginseng ( Shi W. et al, 2021 ; Zhao J. et al, 2021 ; Chen et al, 2022 ; Tu et al, 2022 ). Accumulating studies have shown that quercetin has diverse pharmacological effects, including antioxidant, anti-aging, anti-fungal, anti-tumor, anti-inflammatory, anti-depressant, and hepatoprotective activities ( Arabpour et al, 2021 ; Zou et al, 2021 ; Chen et al, 2022 ).…”