{"paper_id":"04c02d08-0087-4973-ad47-d77bd17e6411","body_text":"Abstract\nFerroptosis is a potential target for the treatment of endometriosis (EMs). The role of andrographolide (AP) in the ferroptosis has gradually attracted attention, but its mechanism of action in endometriosis has not been clarified. Here we investigated the inhibitory effect of AP on endometriosis and its mechanism. Our results showed that AP treatment inhibited progression of ectopic endometrial 12Z cells. We also demonstrated that AP treatment induced ferroptosis and apoptosis in 12Z cells. Combined metabolomics and transcriptomic analysis indicated that AP might exert its effect by down-regulating PSAT1 and PHGDH to inhibit serine synthesis. Knockdown of PSAT1 expression elevated ferroptosis level and blocked progression of 12Z cells; however, the ferroptosis inhibitor Ferrostatin-1 (Fer-1), phosphoserine, or serine mitigated these phenotypes. We also observed that AP inhibited the EMs progression and either PSAT1 or PHGDH level in mice model. Finally, AP exhibited inhibitory effects on the viability of ectopic endometrial stromal cells (EESCs) and the expression of PSAT1, as well as induced ferroptosis in EESCs. Overall, AP is a new potential drug for the treatment of endometriosis.\nSimilar content being viewed by others\nData availability\nUpon reasonable request, the corresponding author will provide access to any data used or analyzed during this study.\nAbbreviations\n- EMs :\n-\nEndometriosis\n- AP :\n-\nAndrographolide\n- Acsl4 :\n-\nAcyl-CoA synthetase long-chain family member 4\n- GPX4 :\n-\nGlutathione peroxidase 4\n- C-Caspase 3 :\n-\nCleaved-caspase 3\n- C-PARP :\n-\nCleaved-PARP\n- CCK-8 :\n-\nCell counting kit—8\n- Fer-1 :\n-\nFerrostatin-1\n- MDA :\n-\nMalondialdehyde\n- ROS :\n-\nReactive oxygen species\n- LDH :\n-\nLactate dehydrogenase\n- LPO :\n-\nLipid peroxidation\n- SiRNA :\n-\nSmall interfering RNA\n- SiNC :\n-\nSmall interfering RNA of negative control\n- SiPAST1 :\n-\nSmall interfering RNA of PAST1\n- 8-OHdG :\n-\n8-Hydroxydeoxyguanosine\n- Ser :\n-\nSerine\n- P-Ser :\n-\nO-Phospho-l-serine\n- E2 :\n-\n17β-Estradiol\nReferences\nAllaire C, Bedaiwy MA, Yong PJ (2023) Diagnosis and management of endometriosis. 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Jiaoyu Li: investigation; writing - original draft. Fei Wang: Data curation; Xiaoying Liu: Investigation. Ruixing Zhang: Investigation. Hongxu Chen: Investigation. Linghui Cheng, Conceptualization; methodology, resource. Zhaolian Wei: Conceptualization; writing - review and editing. Fengyu Zhu: Conceptualization; formal analysis; funding acquisition; writing - review and editing. The authors declare that all data were generated in-house and that no paper mill was used.\nCorresponding authors\nEthics declarations\nEthical approval\nEthical approval for the mice experiments in this study were granted the Ethical Committee and the Institutional Animal Care and Use Committee of Anhui Medical University (license number LLSC20240162).\nCompeting interest\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.\nWei Ye, Nie Zhang, and Jiaoyu Li are co-first authors.\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\nYe, W., Zhang, N., Li, J. et al. Andrographolide blocked the progression of endometriosis by promoting ferroptosis via inhibiting anabolism of serine. Naunyn-Schmiedeberg's Arch Pharmacol 399, 7935–7952 (2026). https://doi.org/10.1007/s00210-025-04905-2\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s00210-025-04905-2","source_license":"CC0","license_restricted":false}