{"paper_id":"a7e8c04b-830d-4b8e-b2e5-3c6720ac677a","body_text":"Abstract\nJuan-Tong-Yin (JTY) is a clinically effective prescription for treating endometriosis (EM). However, its material basis and mechanisms of action are unclear. In this particular investigation, we used both metabolomics and network pharmacology to investigate the material basis and mechanisms underlying the therapeutic effects of JTY in the treatment of EM. In total, 37 blood entry compounds derived from JTY were identified by ultra-performance liquid chromatography-high resolution mass spectrometry technology (UPLC-MS/MS). The intersecting target genes of 101 genes associated with identified compounds in JTY and EM disease genes were identified using a network pharmacology approach. The protein interaction network revealed ESR1, ACTB, TP53, IL6, TNF, BCL2, and STAT3 as important targets. Gene Ontology (GO) analysis showed that negative regulation of apoptotic processes, cell proliferation, positive regulation of ERK1 and ERK2 cascade angiogenesis, positive regulation of I-kappaB kinase/NF-kappaB signaling, positive regulation of cell migration, and inflammatory response were the main functions, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that 20 pathways such as the sphingolipid signaling pathway and PI3K-Akt signaling pathway were the main pathways involved in the anti-EM effects of JTY. 39 potential metabolic markers and 7 possible metabolic pathways were identified by metabolomics analysis. Metabolomic analysis demonstrated that JTY's therapeutic efficacy could be attributed to the modulation of bile acid metabolism, phospholipid metabolism, phospholipid signaling pathways, unsaturated fatty acid biosynthesis. Combined network pharmacological and metabolomic analysis revealed that sphingolipid signaling psssway is a crossed metabolic pathway. Sphingosine-1-phosphate (S1P), sphingosine (Sph), Sphingomyelin (SM) are significantly enriched differential metabolite by the sphospholipid signaling pathway.\nSimilar content being viewed by others\nData Availability\nData is available upon request.\nReferences\nScioscia, M., Bruni, F., Ceccaroni, M., et al. (2011). Distribution of endometriotic lesionsin endometriosis stage IV supports the menstrual reflux theory and requires specific preoperative assessment and therapy. Acta Obstetricia et Gynecologica Scandinavica, 90(2), 136–139. https://doi.org/10.1111/j.1600-0412.2010.01008.x\nTaylor, H. S., Kotlyar, A. M., & Flores, V. A. (2021). Endometriosis is a chronic systemic disease: Clinical challenges and novel innovations. Lancet, 397(10276), 839–852. https://doi.org/10.1016/S0140-6736(21)00389-5\nMedicine, B. M. C. (2023). Shining a light on endometriosis: Time to listen and take action. 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Reproductive Sciences, 30(7), 2040–2059. https://doi.org/10.1007/s43032-023-01167-2\nAcknowledgements\nWe would like to express our sincere gratitude to Guangxi University of Chinese Medicine for their invaluable support and resources throughout this study.\nFunding\nThis project was supported by National Natural Science Foundation of China(No.81960884; No.82460948)&Guangxi Natural Science Foundation (Grant No. 2023GXNSFAA026223)&Self-funded Scientific Research Project of Guangxi Administration of Traditional Chinese Medicine (Grant No. GXZYA20240213).\nAuthor information\nAuthors and Affiliations\nContributions\nPei Guo: designed the experiments, Writing-review & editing, Writing-original draft. Qiyu Liu: Resources, Methodology, Investigation. Jing Li: Data analysis. Shan Li, Wenjia Ding and Qiuling Zhao, Shilang Zhou: Methodology, Investigation. Fengyun Meng, Zhenyu Tang and Weihong Li: Approved the final manuscript.\nCorresponding authors\nEthics declarations\nEthics Approval\nThis study was approved by the Experimental Animal Ethics Committee of Guangxi University of Chinese Medicine (No. DW20221024-209) conducted in accordance with the requirements of the Principles of Laboratory Animal Care.\nConsent to Participate\nAll authors involved in this study provided their informed consent to participate.\nConsent for Publication\nThe authors affirm that all participants have provided their informed consent for the publication of findings derived from this study.\nCompeting interests\nThe authors declare no competing interests.\nAdditional information\nPublisher's Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nRights and permissions\nSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.\nAbout this article\nCite this article\nGuo, P., Liu, Q., Li, J. et al. Integrated Serum Pharmacochemistry, Metabolomics, and Network Pharmacology to Reveal the Material Basis and Mechanism of Juan-tong-yin in the Treatment of Endometriosis. Appl Biochem Biotechnol 198, 3859–3886 (2026). https://doi.org/10.1007/s12010-025-05523-7\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s12010-025-05523-7","source_license":"public-domain-us","license_restricted":false}