{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:55:26Z","timestamp":1775804126930,"version":"3.50.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The prevalence of drug-induced acute liver injury, represented by acetaminophen (APAP), has seriously threatened human lives. Macrophages play an important role in acute liver injury; however, the treatment options remain limited. Therefore, exploring the pathogenesis of the disease and developing new treatment strategies targeted macrophages are particularly important.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study innovatively evaluates the hepatoprotective effects of magnesium isoglycyrrhizinate (MgIG) and elucidates its underlying mechanisms modulating Kupffer cell (KC) inflammation using an APAP-overdose mouse model. Hyperglycaemia was induced in C57BL\/6J mice by streptozotocin treatment, and the mice were randomly divided into Saline, APAP, APAP + NAC, and APAP + MgIG groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The data demonstrated that APAP administration elicited pronounced histopathological injury and markedly upregulated serum transaminases (ALT and AST). Treatment with MgIG ameliorated these histological lesions and suppressed transaminase elevations, paralleling the effect of N-acetylcysteine (NAC). APAP induced oxidative stress in KCs, as evidenced by increased malondialdehyde (MDA) levels, decreased superoxide dismutase (SOD) activity, and a reduction in glutathione (GSH) content. Moreover, APAP exposure significantly impaired autophagy in KCs. MgIG mitigated oxidative damage and restored autophagic activity through the AMPK\/AKT signalling cascade. Notably, combined treatment with MgIG and NAC produced even greater protection against APAP-induced hepatic injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrates that MgIG provides both protective and therapeutic effects in APAP-challenged mice with hyperglycaemia by modulating autophagy and oxidative stress in liver-resident macrophages.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1744099","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:00:14Z","timestamp":1775800814000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Magnesium isoglycyrrhizinate ameliorates acetaminophen-induced acute liver injury with hyperglycaemia by modulating autophagy and oxidative stress in liver-resident macrophages"],"prefix":"10.3389","volume":"17","author":[{"given":"Qingfa","family":"Bu","sequence":"first","affiliation":[{"name":"Department of General Surgery, First Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]},{"name":"Department of General Surgery, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Biological Science and Medical Engineering, Southeast University","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zibo","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bozhou","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of General Surgery, First Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, First Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, First Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuhao","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of General Surgery, First Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, First Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3789","DOI":"10.1016\/j.cell.2024.06.029","article-title":"Diabetes mellitus-progress and opportunities in the evolving epidemic","volume":"187","author":"Abel","year":"2024","journal-title":"Cell."},{"key":"B2","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1080\/10715762.2018.1468564","article-title":"N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why","volume":"52","author":"Aldini","year":"2018","journal-title":"Free Radical Research"},{"key":"B3","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1038\/ncb2788","article-title":"Emerging regulation and functions of autophagy","volume":"15","author":"Boya","year":"2013","journal-title":"Nat. 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