Mechanism of Action of Trichosanthis Fructus-Allii Macrostemonis Bulbus Herb Pairs Against Hyperlipidemia Based on Network Pharmacology / 中国实验方剂学杂志

ABSTRACT

Objective:Based on the hyperlipidemia rat model and network pharmacology technology, the mechanism of action of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs against hyperlipidemia was analyzed. Method:The levels of blood lipids and inflammatory factors were measured through prophylactic administration of low, medium and high-dose Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs in hyperlipidemia rats. The active ingredients of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs were screened out through Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) and text mining. The targets of active ingredients screened through the Swiss Target Prediction, Similarity ensemble approach (SEA), DrugBank database. The disease targets were collected through Therapeutic Target Database (TTD), Online Mendelian Inheritance in Man (OMIM), DrugBank, DisGeNET database. The targets of active ingredients and disease target were integrated, and screened through topological parameters to gain the main candidate targets of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs against hyperlipidemia. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and the gene ontology (GO) functional enrichment analysis were conducted through ClueGO and Database for Annotation, Visualization and Integrated Discovery (DAVID), respectively. The traditional Chinese medicine-chemical ingredient-target network model, and the target-pathway network model were constructed through Cytoscape, and their crosstalk target and signal pathway were analyzed. Result:Animal experiments showed that the prophylactic administration of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs significantly reduced the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) in serum of rats with hyperlipidemia, increased high-density lipoprotein (HDL-C) levels, and inhibited the expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). According to the findings, 27 active ingredients, such as mandenol, diosmetin and α-spinasterol, might be the main active ingredients of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs, 16 crosstalk targets and 10 signal pathways might be the main therapeutic targets and pathways, main targeting apolipoprotein A1 (APOA1), apolipoprotein A2 (APOA2), apolipoprotein C3 (APOC3), lipoprotein lipase (LPL), low-density lipoprotein receptor (LDLR) and other crosstalk targets affected cholesterol metabolism, bile secretion, peroxisome proliferator activated receptor (PPAR) signaling pathway in regulating the lipid level, targeting tumor necrosis factor (TNF), IL-6, interleukin-1β (IL-1β), mitogen-activated protein kinase 1 (MAPK1), C-C motif chemokine 2 (CCL2) and other crosstalk targets affected tumor necrosis factor (TNF) signaling pathway, Toll-like receptor signaling pathway, interleukin-17 (IL-17) signaling pathway, and hypoxia inducible factor (HIF) signaling pathway in regulating the inflammatory factor level. The DAVID database for GO enrichment analysis showed that the hyperlipidemia was treated mainly through biological processes, such as inflammation, lipid localization, storage and lipid metabolism. Conclusion:These findings can predict the mechanism of action of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs against hyperlipidemia, and provide a theoretical basis for the material basis and clinical application of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs.