Abstract:

Objective To analyze the improvement effect of monk fruit on diabetic nephropathy（DN） by network pharmacology，and to elucidate its possible related mechanism. Methods The Traditional Chinese Medicine Systems Pharmacology（TCMSP） Database was used to detect the active ingredients and their targets of monk fruit； the DN target genes were screened out by DisGeNET Database and Genecards Database； the key targets of monk fruit against DN were obtained by comparing the monk fruit with DN targets； protein-protein interaction （PPI） network diagram was constructed by STRING Database and Cytoscape software； Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway enrichment analysis were performed by Cytoscape software.Molecular docking technology was used to predict the binding abilities of the core targets and the main active ingredients of monk fruit. Results The TCMSP Database combined with the selection criteria was used to screen out a total of five active ingredients of monk fruit （ZINC03860434， Perlolyrine， beta-sitosterol， Kaempferol， and Flazin） as well as 85 targets represented by serine/threonine protein kinase 1 （AKT1），transcription factor RELA， c-Jun N-terminal kinase （JUN），and tumor necrosis factor （TNF）. Among them， Kaempferol contained the most targets.Among the 85 targets， 34 were associated with DN.The GO functional enrichment analysis mainly included biological process（BP） such as oxidative stress， regulation of inflammation and apoptosis， and cell signaling transduction.The KEGG enrichment analysis included advanced glycosylation end product（AGE）-receptor of AGE （AGE-RAGE） signaling pathway， TNF signaling pathway， and C-type lectin receptor signaling pathway.The results molecular docking technology of the main active ingredients of monk fruit and DN target proteins showed that 5 kinds of molecular docking engergy were －8.00－－5.00 kJ·mol^－1. Conclusion Kaempferol is the most effective active ingredient in the monk fruit for the treatment of DN， and its mechanism is mainly related to anti-inflammatory.

Key words: Monk fruit, Diabetic nephropathy, Network pharmacology, Inflammation factor, Protein-protein interaction