Table3_Exploration of the Modulatory Property Mechanism of ELeng Capsule in the Treatment of Endometriosis Using Transcriptomics Combined With Systems Network Pharmacology.DOC

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.

子宫内膜异位症（Endometriosis）是一种常见的妇科疾病，可引发严重的慢性盆腔疼痛与不孕不育。越来越多的研究证据表明，中医药（traditional Chinese medicine, TCM）在子宫内膜异位症的治疗中具有积极作用。莪棱胶囊（ELeng Capsule, ELC）是一款已在子宫内膜异位症临床治疗中应用多年的中药复方，但其作用机制尚未得到充分阐释。本研究采用网络药理学与mRNA转录组分析方法，对莪棱胶囊的多项治疗靶点展开探究。研究共鉴定出40种活性成分，其中75个靶点与子宫内膜异位症相关蛋白存在重叠。基于网络药理学分析结果，莪棱胶囊治疗子宫内膜异位症的核心机制围绕三大功能模块：诱导细胞凋亡、抑制血管生成、调节免疫，具体涉及信号分子与相互作用通路（神经活性配体-受体相互作用）、免疫系统相关通路（Toll样受体信号通路）、血管内皮生长因子（vascular endothelial growth factor, VEGF）信号通路及丝裂原活化蛋白激酶（mitogen-activated protein kinase, MAPK）信号通路。此外，通过RNA测序分析，本研究发现莪棱胶囊的作用机制还主要与肌动蛋白及细胞骨架功能模块调控、上皮间质转化（epithelial–mesenchymal transition, EMT）、黏着斑以及免疫相关通路的调控密切相关。综上，莪棱胶囊对子宫内膜异位症具有明确的治疗获益，其潜在作用机制可通过诱导细胞凋亡、调节血管生成、调控细胞骨架及上皮间质转化等功能模块得以实现。本研究不仅为中医药治疗子宫内膜异位症的作用机制提供了全新的研究视角，同时也为从传统草药中发掘与开发新药提供了高效可行的研究范式。