{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:59:31Z","timestamp":1787504371719,"version":"build-2736575974"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Acetaminophen (APAP) is a major cause of acute liver injury (ALI), and N\u2010acetylcysteine is the only approved detoxification drug. Nimbolide (Nim), which is isolated from the neem tree (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Azadirachta indica<\/jats:italic>\n                    <\/jats:styled-content>\n                    ), possesses protective properties against multiple diseases, including pancreatitis, autoimmune hepatitis, arthritis, and diabetic cardiomyopathy. Here, we investigated the protective effect of nimbolide on APAP\u2010induced ALI. Male C57BL\/6J mice were used to establish an ALI model via APAP administration (500\u2009mg\/kg, i.p.). All the mice received nimbolide (20\u2009mg\/kg, i.p.) or a vehicle 2\u2009h before APAP injection. Blood and liver samples were collected at the indicated times. As expected, Nim treatment alleviated APAP\u2010induced liver injury and inflammation in the mice. Moreover, Nim inhibited APAP\u2010induced apoptosis by regulating endoplasmic reticulum (ER) stress. We further revealed that Nim improved mitochondrial function and increased Sirtuin 1 (SIRT1) expression. However, the protective effects of Nim were partially blocked by SIRT1 knockdown via siRNA in\u00a0vitro. Our study revealed that nimbolide alleviated APAP\u2010induced ALI by inhibiting oxidative stress and ER stress via SIRT1 activation.\n                  <\/jats:p>","DOI":"10.1002\/prp2.70120","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:24:26Z","timestamp":1747355066000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Nimbolide Targeting\n                    <scp>SIRT1<\/scp>\n                    Protects Against Acetaminophen\u2010Induced Acute Liver Injury by Regulating Oxidative Stress and Endoplasmic Reticulum Stress"],"prefix":"10.1002","volume":"13","author":[{"given":"Junhui","family":"Ba","sequence":"first","affiliation":[{"name":"Department of Medical Intensive Care Unit Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou 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