Study on network pharmacology mechanism of Leonurus japonicus in treating dysmenorrhea caused by cold coagulation and blood stasis / 中草药

ABSTRACT

Objective: To establish a chemical constitution-disease target-metabolic signaling pathway network of Leonurus japonicus, and explore the mechanism of multi-component, multi-target and multi-pathway of L. japonicus for the treatment of dysmenorrhea caused by cold coagulation and blood stasis. Methods: TCMSP database and Swiss Target Prediction server were used to obtain the chemical components and action targets of L. japonicus. Combined with DrugBank, DisGeNET, TTD and other databases, the action targets of L. japonicus for treating dysmenorrhea symptoms wtih cold coagulation and blood stasis were obtained. Through DAVID's website, GO function enrichment analysis and KEGG pathway analysis were conducted on the targets, and cytoscape 3.6.0 was used to construct the network diagram of the active component-dysmenorrhea target-metabolic signaling pathway of L. japonicus, to explore the mechanism of action of L. japonicus in treating dysmenorrhea with cold coagulation and blood stasis. Furthermore, Western blotting experiments were conducted to verify the effect of L. japonicus on the expression of PTGS1 and PTGS2 proteins in the uterine tissues of the model rats with cold coagulation and blood stasis dysmenorrhea. Results: Eight potential active ingredients of L. japonicus were obtained, including 22 dysmenorrhea related disease targets, main targets PTGS1, PTGS2, ALOX5, PLAG2A, AKR1C3, etc. A total of 71 GO items were obtained by GO functional enrichment analysis (P < 0.05), including 46 biological process (BP) items, four cell component (CC) items, and 21 molecular function (MF) items. There were 22 possible targets for the treatment of dysmenorrhea, and seven signaling pathways were obtained through KEGG pathway enrichment and screening (P < 0.05), involving arachidonic acid metabolism, linoleic acid metabolism, steroid hormone biosynthesis, etc. L. japonicus significantly increased the protein expression levels of PTGS1 and PTGS2 in the uterus of the model rats (P < 0.05), which confirmed some of the predicted results of network pharmacology. Conclusion: L. japonicus may treat dysmenorrhea with cold coagulation and blood stasis by acting on arachidonic acid metabolism pathway.