Exploration of the Modulatory Property Mechanism of ELeng Capsule in the Treatment of Endometriosis Using Transcriptomics Combined With Systems Network Pharmacology

Abstract

Endometriosis is a common gynecological disease and causes severe chronic pelvic pain and infertility. Growing evidence showed that traditional Chinese medicine (TCM) plays an active role in the treatment of endometriosis. ELeng Capsule (ELC) is a Chinese medicine formula used for the treatment of endometriosis for several years. However, the mechanisms of ELC have not been fully characterized. In this study, network pharmacology and mRNA transcriptome analysis were used to study various therapeutic targets in ELC. As a result, 40 compounds are identified, and 75 targets overlapped with endometriosis-related proteins. The mechanism of ELC for the treatment of endometriosis is based on the function modules of inducing apoptosis, inhibiting angiogenesis, and regulating immunity mainly through signaling molecules and interaction (neuroactive ligand–receptor interaction), immune system–associated pathways (toll-like receptor signaling pathway), vascular endothelial growth factor (VEGF) signaling, and MAPK signaling pathway based on network pharmacology. In addition, based on RNA-sequence analysis, we found that the mechanism of ELC was predominantly associated with the regulation of the function modules of actin and cytoskeleton, epithelial–mesenchymal transition (EMT), focal adhesion, and immunity-associated pathways. In conclusion, ELC exerted beneficial effects on endometriosis, and the potential mechanism could be realized through functional modules, such as inducing apoptosis and regulating angiogenesis, cytoskeleton, and EMT. This work not only provides insights into the therapeutic mechanism of TCM for treating endometriosis but also offers an efficient way for drug discovery and development from herbal medicine.

The involvement of RNA N6‐methyladenosine and histone methylation modification in decidualization and endometriosis‐associated infertility

“…ChIP‐Seq was conducted in three human primary ESCs with Sh‐EZH2 or Sh‐NC treatment, and the differentially expressed pathways enriched in the EZH2 knockdown group are summarised in Figure S 1B . The enriched pathways, such as cytokine–cytokine receptor interaction, cell adhesion molecules, cAMP signalling pathway, neuroactive ligand–receptor interaction and calcium signalling pathway, are not only associated with EM pathogenesis, 39 , 40 , 41 , 42 , 43 , 44 but also may participate in the dysregulated decidualization of EM. 45 , 46 Further ChIP‐PCR results showed that there was reduced binding of the H3K27Me3 antibody to the IGFBP1 promoter in human primary ESCs with EZH2 depletion (Figure 1D ).…”

Multi-omics technology for demystifying herbal medicine

“…The modulatory mechanism of ELeng capsule for endometriosis treatment was explored by transcriptomics. The potential mechanism was related with functional molecules including the regulating angiogenesis and inducing apoptosis [24]. The therapeutic mechanism of a traditional formula Qingfei Xiaoyan Wan in the suppression of allergic asthma was evaluated by ranscriptomics analysis and screened out six genes with the highest values and the differentially expressed genes were mainly enriched in cytokine signaling pathway and inflammatory response [25].…”

Introductory Chapter: Endometriosis - Recent Advances, New Perspectives and Treatments

“…This study pointed out that GZFLC regulates endometriosis by modulating metabolites changes of glycolysis or gluconeogenesis and then the expression of transforming growth factor-beta 1 (TGF-β1), glucose transporter-4 (GLUT-4), and VEGF [35]. Network pharmacology and mRNA transcriptome analysis were performed to study ELeng Capsule (ELC), another Chinese medicine formula that has been used for the treatment of endometriosis [36]. Based on network pharmacology, the ELC mechanisms involve neuroactive ligand-receptor interaction, toll-like receptor, VEGF and MAPK signaling pathways related to apoptosis, angiogenesis inhibition, and immune regulation.…”

“…Based on network pharmacology, the ELC mechanisms involve neuroactive ligand-receptor interaction, toll-like receptor, VEGF and MAPK signaling pathways related to apoptosis, angiogenesis inhibition, and immune regulation. Moreover, based on RNA-sequence analysis, ELC effects were related to regulation of cytoskeleton, epithelial-mesenchymal transition, and focal adhesion [36].…”