Exploration of  the mechanisms of Cyperi Rhizoma in the treatment of endometriosis through GEO datasets, network pharmacology, and molecular docking studies

AbstractCyperi rhizoma (CR) has traditionally been used to treat endometriosis (EMS), but its molecular mechanism remains unclear. To address this, we used a multi-faceted approach that included analysis of GEO datasets, network pharmacology, molecular docking and in vitro experiments.CR components and their potential targets were identified using TCMSP and PubChem, while GEO datasets, GeneCards, and DisGeNET were used to retrieve EMS-related targets. Compound-target and protein-protein interaction networks were constructed using Cytoscape and STRING, respectively, and hub genes were identified using CytoHubba. Enrichment analysis and molecular docking were performed, and RT-qPCR and Western blotting were used to assess protein expression levels. According to our research, there are 18 active CR components and 34 possible anti-EMS targets. Network analysis identified quercetin and kaempferol as potential key chemicals and revealed IL6, MMP9, CCL2, CXCL8, ICAM1, L10, VCAM1, IL18, SELE and TIMP1 as central hub genes in the network. GO, KEGG and GSEA analyses showed that ICAM1 and VCAM1 are involved in "positive regulation of cell adhesion", TNF signalling pathway, NF-kappa B signalling pathway and "GO_INFLAMMATORY_RESPONSE". Analysis of the GEO datasets revealed that ICAM1 and VCAM1 were upregulated in endometriosis compared to controls. Molecular docking showed that quercetin and kaempferol have strong binding affinities for these proteins. RT-qPCR and Western blotting analyses showed that CR treatment suppressed ICAM1 and VCAM1 expression, leading to reduced inflammation and adhesion in endometriosis-associated symptoms. Thus, these results provide a novel rationale for the potential of CR in the treatment of EMS.