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Pharmacol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Endometriosis (EMs) is characterized by ectopic growth of active endometrial tissue outside the uterus. The Luoshi Neiyi prescription (LSNYP) has been extensively used for treating EMs in China. However, data on the active chemical components of LSNYP are insufficient, and its pharmacological mechanism in EMs treatment remains unclear. This study aimed to explore the potential mechanism of LSNYP for EMs through network pharmacology based on the components absorbed into the blood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used to analyze blood components, and a series of network pharmacology strategies were utilized to predict targets of these components and EMs. Protein\u2013protein interaction (PPI) network analysis, component\u2013target\u2013disease network construction, gene ontology (GO) functional enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Additionally, molecular docking, molecular dynamics simulations, and <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> experiments were conducted to validate the HIF1A\/EZH2\/ANTXR2 pathway associated with hypoxic pathology in EMs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty-four absorbed components suitable for network pharmacology analysis were identified, and core targets, such as interleukin 6, EGFR, HIF1A, and EZH2, were founded. Enrichment results indicated that treatment of EMs with LSNYP may involve the regulation of hypoxia and inflammatory-related signaling pathways and response to oxidative stress and transcription factor activity. Experimental results demonstrated that LSNYP could decrease the expression of HIF1A, ANTXR2, YAP1, CD44, and \u03b2-catenin, and increased EZH2 expression in ectopic endometrial stromal cells and endometriotic tissues. Molecular docking and molecular dynamics simulations manifested that there was stable combinatorial activity between core components and key targets of the HIF1A\/EZH2\/ANTXR2 pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>LSNYP may exert pharmacological effects on EMs via the HIF1A\/EZH2\/ANTXR2 pathway; hence, it is a natural herb-related therapy for EMs.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2024.1395160","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T04:53:12Z","timestamp":1722228792000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Potential mechanism of Luoshi Neiyi prescription in endometriosis based on serum pharmacochemistry and network pharmacology"],"prefix":"10.3389","volume":"15","author":[{"given":"Lizheng","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjun","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangwen","family":"Jing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjin","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangli","family":"Pei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"B2","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1111\/imcb.12212","article-title":"IL-6 mediates ER expansion during hyperpolarization of alternatively activated macrophages","volume":"97","author":"Ayaub","year":"2019","journal-title":"Immunol. 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