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Neutrophil extracellular traps (NETs) formation bridges these two pathological processes. Through both in vivo and in vitro experiments, it is observed that Emodin, a natural anthraquinone derivative derived from Dahuang, significantly ameliorates the cytokine storm and coagulation abnormalities induced by sepsis, demonstrating remarkable efficacy in inhibiting NETs formation. Furthermore, through protein microarrays, surface plasmon resonance (SPR), pull\u2010down assays, and molecular docking analyses, BCL\u201010 is established as a direct target of Emodin, providing protective effects in both in vivo and in vitro settings. Through conditional knockout of BCL\u201010 in neutrophils, alongside single\u2010cell sequencing analyses, it is confirmed that BCL\u201010 is key in promoting excessive NET formation in sepsis. Additionally, Emodin exerts powerful protective effects by modulating the function of the BCL\u201010\/MALT1 complex, thereby alleviating the NF\u2010\u03baB signaling activation and inhibiting NETs formation. Collectively, these findings provide pharmacological evidence that Emodin targeted BCL\u201010 regulates the BCL\u201010\/MALT1 complex and suppresses NF\u2010\u03baB activation, ultimately conferring significant multiorgan protective effects in sepsis. The conduct of this study provides new clues for the translational research of Emodin and its target BCL\u201010 in sepsis.<\/jats:p>","DOI":"10.1002\/advs.202417129","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T15:03:57Z","timestamp":1754665437000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Emodin Alleviates Sepsis\u2010Induced Multiorgan Damage by Inhibiting NETosis through Targeting Neutrophils BCL\u201010"],"prefix":"10.1002","volume":"12","author":[{"given":"Xiaolong","family":"Xu","sequence":"first","affiliation":[{"name":"Beijing Hospital of Traditional Chinese Medicine Capital Medical University Beijing Institute of Chinese Medicine Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Diseases  Beijing 100010 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