{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:07:42Z","timestamp":1790168862638,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Food Science &amp;amp; Nutrition"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study aimed to elucidate the therapeutic mechanisms of Exocarpium Citri Grandis (ECG) against lipopolysaccharide (LPS)\u2010induced acute liver injury (ALI) using an integrated approach combining network pharmacology and experimental validation. The chemical profile of ECG was characterized via UHPLC\u2010Q\u2010Exactive MS. Male C57BL\/6J mice were employed to establish an LPS\u2010induced ALI murine model for evaluating hepatoprotective effects of ECG. Serum AST\/ALT levels, histopathology changes, and inflammatory, apoptotic, oxidative, and ferroptotic markers were analyzed. Additionally, network pharmacology was used to identify the targets and pathways of ECG, while molecular docking validated interactions between bioactive compounds and key regulatory molecules. ECG treatment significantly reduced serum AST\/ALT levels (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05\u20130.001) and alleviated hepatic inflammation and necrosis. Moreover, qPCR and Western blotting revealed that ECG markedly downregulated pro\u2010inflammatory cytokines (IL\u20106, IL\u20101\u03b2, TNF\u03b1), inhibited cellular inflammation by downregulating the expression of proteins related to the TLR4\/MyD88 pathway, counteracted oxidative stress by increasing Nrf2 nuclear translocation and the expression of genes such as NQO1, GCLC, and GCLM, suppressed apoptosis via modulation of Bax\/Bcl2\/CASP3, and inhibited ferroptosis by normalizing iron content and GPX4\/SLC7A11 expression. Network pharmacology identified 127 shared targets between ECG and sepsis, highlighting critical pathways including TNF, p53, and IL\u201017 signaling. Molecular docking confirmed strong binding affinities (e.g., naringin with TP53: \u221213.23\u2009kcal\/mol) between ECG\u2010derived flavonoids and coumarins with apoptosis and inflammation regulators. ECG mitigates LPS\u2010induced ALI through coordinated anti\u2010inflammatory, anti\u2010apoptotic, anti\u2010oxidative, and anti\u2010ferroptotic mechanisms, mediated via multi\u2010target modulation of critical pathways. These findings underscore the potential of ECG as a natural therapeutic candidate for ALI, thus warranting further clinical exploration.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.71012","type":"journal-article","created":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T04:14:38Z","timestamp":1758946478000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Exocarpium Citri Grandis Attenuates Lipopolysaccharide\u2010Induced Acute Liver Injury Through Suppression of Inflammatory, Apoptotic, Oxidative, and Ferroptotic Pathways"],"prefix":"10.1002","volume":"13","author":[{"given":"Guoni","family":"Zhang","sequence":"first","affiliation":[{"name":"Haikou Hospital of Traditional Chinese Medicine  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Li","sequence":"additional","affiliation":[{"name":"Science and Technology Innovation Center Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaibin","family":"Xu","sequence":"additional","affiliation":[{"name":"Science and Technology Innovation Center Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaili","family":"Zhou","sequence":"additional","affiliation":[{"name":"Science and Technology Innovation Center Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Fifth Clinical Medical College of Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqin","family":"Wu","sequence":"additional","affiliation":[{"name":"Science and Technology Innovation Center Guangzhou University of Chinese Medicine  Guangzhou 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Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7014-3643","authenticated-orcid":false,"given":"Zhitong","family":"Deng","sequence":"additional","affiliation":[{"name":"Haikou Hospital of Traditional Chinese Medicine  Haikou 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