To explore the active ingredients and molecular mechanisms of Yishen-Jianpi-Lishui recipe (Shenyanshu tablet, SYST) in the treatment of glomerulonephritis by the network pharmacology and molecular docking methods.

Through the analysis platform of Traditional Chinese Medicine Systems Pharmacology (TCMSP), the main active ingredients of the 7 main Chinese medicines (Atractylodes, Poria, Imperata, ginseng, wolfberry, honeysuckle, and dandelion) in the recipe were queried, and their targets were also predicted. The databases were searched including the human gene database (GeneCards), the database of Online Mendelian Inheritance in Man (OMIM), the Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB), the Therapeutic Target Database (TTD), and the drug action target database (DrugBank). The UniProt database was used to annotate all targets proteins. The intersection of the active ingredients′ targets and diseases′ targets were taken as the potential targets for the treatment of glomerulonephritis by SYST, for which the gene ontology (GO) database and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were applied for the pathway enrichment analysis, and the core active ingredients and core targets obtained were analyzed with the molecular docking method.

A total of 81 active ingredients, 219 gene targets, 1, 952 glomerulonephritis-related targets, and 116 potential targets proteins for the treatment of glomerulonephritis with SYST were screened out. The GO enrichment analysis results suggested that the potential targets proteins for the treatment of glomerulonephritis with SYST were mainly involved in the biological processes such as lipopolysaccharide reaction, bacterial-derived molecular reaction, oxidation reaction, and cytochemical pressure reaction. The KEGG enrichment analysis results suggested that possible pathways included the lipid and atherosclerosis pathways, the advanced glycation end products (AGEs) and the receptor for AGE (RAGE) signaling pathways for diabetic complications, hepatitis B-related pathways, and Kaposi′s sarcoma-related herpes virus infection pathways, etc. The Protein-Protein Interaction (PPI) network analysis showed that SYST could act in the treatment of glomerulonephritis through 12 key targets including MYC, JUN, MAPK8, FOS, NR3C1, TP53, MAPK14, IL-2, MAPK1, AKT1, TNF, and RELA. The molecular docking results indicated that the main active components of SYST combined well with a variety of targets proteins for the treatment of glomerulonephritis (S>4.5).

The results of this study suggested that SYST has the characteristics of multiple components, multiple targets, and multiple pathways in the treatment of glomerulonephritis, which laid a research foundation for further elucidating its pharmacological mechanism and developing new drugs.