{"paper_id":"0191709d-13c1-4520-bd31-dac43fc2720c","body_text":"Abstract\nBackground\nPyroptosis has been reported to occur in several diseases, such as atherosclerosis, nonalcoholic steatohepatitis, and endometriosis. Although fucoxanthin has several biological properties (particularly anti-inflammatory properties), the mechanism through which fucoxanthin modulates or inhibits pyroptosis pathways is unclear. The present study aimed to determine whether fucoxanthin ameliorate endometriosis by preventing macrophage pyroptosis.\nMethods and results\nA model of localized cell death in M2 macrophages induced by lipopolysaccharide (LPS) and adenosine triphosphate (ATP) was developed. Fucoxanthin decreased the ATP- and LPS-induced pyroptosis of M2 macrophage. Pretreatment with fucoxanthin alleviated oxidative stress and decreased the release of Reactive Oxygen Species (ROS) and LDH from M2 macrophages. Fucoxanthin pretreatment decreased the mRNA expression levels of GSDMD, NLRP3, caspase-1, IL-18, and IL-1β and inhibited the activation of the NLRP3 inflammasome and decreased the protein expression levels of Caspase-1 and GSDMD. In addition, fucoxanthin treatment reduced inflammatory signalling and decreased the expression and release of the IL-18 and IL-1β inflammatory factors.\nConclusions\nFucoxanthin prevents macrophage pyroptosis by inhibiting the mammalian target of rapamycin (mTOR), protein kinase B (AKT), and phosphatidylinositol 3-kinase (PI3K) signalling pathway.\nClinical Trial Registration\nClinical trial number: not applicable\nSimilar content being viewed by others\nData availability\nNo datasets were generated or analysed during the current study.\nReferences\nTaylor HS, Kotlyar AM, Flores VA (2021) Endometriosis is a chronic systemic disease: clinical challenges and novel innovations [J]. 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Reprod Biomed Online 46(3):425–435. https://doi.org/10.1016/j.rbmo.2022.11.006\nAcknowledgements\nThis study was partially supported by the Bengbu Medical University.\nFunding\nThis work was supported by the Bengbu Medical University Graduate Student Research and Innovation Program Project (Byycx23087).\nAuthor information\nAuthors and Affiliations\nContributions\nAll authors contributed to the study conception and design. Material preparation was prepared by Taotao Rong. Data collection was performed by Ziwei Pei, Mingjuan Zhang and Lili Lv. The first draft of the manuscript was written by Ziwei Pei. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\nCorresponding author\nEthics declarations\nCompeting interests\nThe authors declare no competing interests.\nEthics approval\nThis article does not contain any studies with human participants or animals performed by any of the authors.\nAdditional information\nPublisher’s note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nSupplementary Information\nBelow is the link to the electronic supplementary material.\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\nPei, Z., Zhang, M., Rong, T. et al. Fucoxanthin regulates macrophage pyroptosis through the PI3K/AKT/mTOR signalling pathway. Mol Biol Rep 53, 250 (2026). https://doi.org/10.1007/s11033-025-11408-z\nReceived:\nAccepted:\nPublished:\nVersion of record:\nDOI: https://doi.org/10.1007/s11033-025-11408-z","source_license":"public-domain-us","license_restricted":false}