Mechanism of Modified Danggui Shaoyao Powder in Treatment of Dysmenorrhea of Endometriosis Based on Network Pharmacology and Experimental Verification
Objective:To explore the mechanism of modified Danggui Shaoyao Powder in treating dysmenorrhea of endometriosis(EMs)based on network pharmacology.Methods:The active ingredients and potential targets of the formula were analyzed using various databases,including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Online Mendelian Inheritance in Man(OMIM),GeneCards,DisGeNET,and the Therapeutic Target Database(TTD).A network of active ingredients of modified Danggui Shaoyao Powder and EMs dysmenorrhea targets was constructed,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed for core targets.Molecular docking between potential active ingredients and core targets was conducted using Autodock Vina software.Real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)and western blot were used to preliminarily verify the effect of the for-mula on mRNA and related protein expression in the endometrium of the EMs mouse model.Results:A total of 86 active ingredi-ents were screened from the formula,corresponding to 64 intersecting targets for the treatment of EMs dysmenorrhea.High-degree targets included epidermal growth factor receptor(EGFR),tumor suppressor gene p53(TP53),prostaglandin-endoperoxide synthase 2(PTGS2),vascular endothelial growth factor A(VEGFA),serine/threonine protein kinase 1(AKT1),interleukin-6(IL-6),che-mokine ligand 8(CXCL8),and matrix metalloproteinase 9(MMP9).GO functional enrichment analysis yielded 1 990 entries,and KEGG pathway analysis involved 127 pathways such as estrogen and focal adhesion.Molecular docking results indicated that quer-cetin,a core component of the formula,had good binding affinity with key targets such as VEGFA,AKT1,and hypoxia-inducible factor 1A(HIF1A).Validation experiments showed that modified Danggui Shaoyao Powder significantly downregulated the mRNA levels of VEGFA,CXCL8,and TP53,as well as the protein levels of MMP9 and cyclooxygenase-2(COX-2)in the EMs mouse mod-el.Conclusion:The core components of modified Danggui Shaoyao Powder can modulate multiple targets related to EMs dysmenor-rhea,and the underlying mechanism of action may involve the regulation of cell invasion,estrogen,immune,and inflammatory re-sponse signaling pathways.
万方数据
维普
