{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T09:27:06Z","timestamp":1786958826443,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":228,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["Mediators of Inflammation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>Liver cirrhosis represents the irreversible end\u2010stage of various chronic liver diseases, whereas hepatic fibrosis, characterized by hepatic stellate cell (HSC) activation, constitutes the critical pathological intermediate in this progression. In this study, we investigated the antifibrotic effects of loganin, a natural iridoid glycoside, and elucidated its underlying mechanisms in bile duct ligation (BDL)\u2013induced cholestatic liver injury and hepatic fibrosis and in TGF\u2010\u03b21\u2013stimulated HSCs. Sprague\u2013Dawley rats subjected to BDL surgery received loganin for 14 days, resulting in marked amelioration of hepatomegaly, inflammatory infiltration, hepatocyte necrosis, and collagen deposition, alongside restoration of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (T\u2010BIL) levels and suppression of fibrogenic gene expression (collagen type I alpha 1 chain [COL1\u03b11], alpha\u2010smooth muscle actin [\u03b1\u2010SMA], and fibronectin). Moreover, loganin attenuated hepatic autophagy, as evidenced by reduced Beclin\u20101 expression and LC3B\u2010II\/I ratio, with decreased colocalization of \u03b1\u2010SMA and LC3B. Bioinformatics analysis and molecular docking indicated that epidermal growth factor receptor (EGFR) may be the target protein through which loganin exerts its antifibrotic effect. Experimental validation demonstrated that loganin suppressed BDL\u2010induced EGFR phosphorylation in vivo. In TGF\u2010\u03b21\u2013activated HSC\u2010T6 cells, loganin inhibited cell activation, downregulated fibrosis markers, impaired autophagic flux, and suppressed TGF\u2010\u03b21\u2013induced upregulation of Beclin\u20101 and LC3B\u2010II\/I. Critically, cotreatment with the EGFR agonist EGF reversed the autophagy\u2010inhibitory and antifibrotic effects of loganin, whereas the EGFR inhibitor AG\u20101478 mimicked loganin\u2019s actions, confirming EGFR signaling as the functional mediator. Overall, these results indicated that loganin could alleviate liver injury and hepatic fibrosis in BDL rats by inhibiting autophagy and activation of HSCs, and this protective effect is mediated by the EGFR pathway.<\/jats:p>","DOI":"10.1155\/mi\/7967581","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:47:19Z","timestamp":1786956439000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Loganin Ameliorates Cholestatic Liver Fibrosis by Inhibiting Hepatic Stellate Cell Autophagy and Activation Through EGFR Signaling"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5352-9932","authenticated-orcid":false,"given":"Xinwen","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2786-8098","authenticated-orcid":false,"given":"Huiling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1099-1360","authenticated-orcid":false,"given":"Chao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2001-4032","authenticated-orcid":false,"given":"Xiaomin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8332-8002","authenticated-orcid":false,"given":"Jiefeng","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"e_1_2_11_1_2","first-page":"759","article-title":"Cirrhosis: Diagnosis and Management","volume":"100","author":"Smith A.","year":"2019","journal-title":"American Family Physician"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells9040875"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2018.09.002"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-021-00754-w"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24282"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2017.11.010"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2011.08.004"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.678886"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154030"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2022.077"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.03.003"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i23.7312"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.12.044"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.07.010"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232415873"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2015.04.037"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.3791\/52438-v"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.04.044"},{"key":"e_1_2_11_21_2","first-page":"214","article-title":"Bcl-2: Beclin 1 Complex: Multiple, Mechanisms Regulating Autophagy\/Apoptosis Toggle Switch","volume":"2","author":"Marquez R. T.","year":"2012","journal-title":"American Journal of Cancer Research"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2014.2383"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1665648"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.26010"},{"key":"e_1_2_11_25_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200102083440610"},{"key":"e_1_2_11_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200102083440604"},{"key":"e_1_2_11_27_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66028"},{"key":"e_1_2_11_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2008.06.013"},{"key":"e_1_2_11_29_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.46360"},{"key":"e_1_2_11_30_2","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X17500070"},{"key":"e_1_2_11_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.10.026"},{"key":"e_1_2_11_32_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-020117-043617"},{"key":"e_1_2_11_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13787"},{"key":"e_1_2_11_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2010.97"},{"key":"e_1_2_11_35_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00423.2015"},{"key":"e_1_2_11_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700532"},{"key":"e_1_2_11_37_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2020.4778"}],"container-title":["Mediators of Inflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/mi\/7967581","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/mi\/7967581","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/mi\/7967581","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:47:21Z","timestamp":1786956441000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/mi\/7967581"}},"subtitle":[],"editor":[{"given":"Jasbir","family":"Arora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/mi\/7967581"],"URL":"https:\/\/doi.org\/10.1155\/mi\/7967581","archive":["Portico"],"relation":{},"ISSN":["0962-9351","1466-1861"],"issn-type":[{"value":"0962-9351","type":"print"},{"value":"1466-1861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"7967581"}}