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Alkaloids are known to modulate autophagy, a mechanism associated with liver protection. Epiisopilosine (EPIIS) and epiisopiloturine (EPI), imidazole alkaloids derived from\n                    <jats:italic>Pilocarpus microphyllus<\/jats:italic>\n                    (Jaborandi), exhibit anti\u2010inflammatory and hepatic immunomodulatory effects. Therefore, this study aimed to compare the hepatoprotective and autophagy\u2010modulating effects of EPI and EPIIS in a murine model of APAP\u2010induced hepatotoxicity. In the experimental design, male BALB\/c mice received APAP (750\u2009mg\/kg, i.p.) to induce hepatotoxicity, followed by phosphate\u2010buffered saline (PBS), N\u2010acetylcysteine (NAC\u2010318 mg\/kg, i.p.), or alkaloids (0.3, 1, or 3\u2009mg\/kg, i.p.) 30\u2009min later. To assess the involvement of autophagy, hydroxychloroquine (HCQ; 80\u2009mg\/kg, i.p.), an autophagy inhibitor, was administered 2\u2009h before APAP. Treatment with EPI, EPIIS, or NAC significantly reduced liver toxicity (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). APAP\u2010treated mice exhibited marked centrilobular necrosis, which was markedly reduced following the treatment with Jaborandi alkaloids. Furthermore, EPIIS and EPI significantly reduced the inflammatory and oxidative markers. Administration of HCQ 2\u2009h before APAP abolished these effects. Western blotting analysis revealed increased LC3B expression, a marker of autophagy, in the hepatic tissues of the treated mice, indicating that EPIIS and EPI modulate autophagy. Molecular docking analysis suggested potential interactions between the alkaloids and CXCL10, a chemokine linked to inflammation and autophagy inhibition. These findings demonstrate that EPIIS and EPI protect against APAP\u2010induced hepatotoxicity in mice, potentially by modulating autophagy and reducing inflammation.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70782","type":"journal-article","created":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T17:21:22Z","timestamp":1773595282000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Imidazole Alkaloids Epiisopilosine and Epiisopiloturine Attenuate Acetaminophen\u2010Induced Liver Toxicity in Mice via Autophagy Modulation and Anti\u2010Inflammatory Effects"],"prefix":"10.1002","volume":"40","author":[{"given":"Ana Patricia","family":"de Oliveira","sequence":"first","affiliation":[{"name":"Laboratory of Inflammation and Translational Gastroenterology (LIGAT) Federal University of Delta do Parna\u00edba (UFDPar) Parna\u00edba 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