{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T16:59:37Z","timestamp":1785085177182,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007452","name":"Wu Jieping Medical Foundation","doi-asserted-by":"publisher","award":["320.6750.2025\u201026\u20108"],"award-info":[{"award-number":["320.6750.2025\u201026\u20108"]}],"id":[{"id":"10.13039\/100007452","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Metabolic\u2010associated fatty liver disease (MAFLD) is the most common chronic liver disease in the world, which lacks effective therapies. Hu Gan Tang (HGT), a modified formulation of the traditional Chinese prescription Si Jun Zi Tang based on the principle of \u201cstrengthening the spleen, resolving dampness, and purging turbidity,\u201d has been clinically used for MAFLD, but the underlying mechanism remains unclear. This study investigated whether HGT mitigates hepatic lipid deposition by enhancing autophagy via the AMPK\/mTOR signaling pathway in vivo and in vitro. HGT significantly ameliorated hepatic injury, reduced lipid accumulation, and upregulated autophagy, evidenced by increased Beclin\u20101, Atg5, LAMP1, and LC3B\u2010II\/I ratio alongside decreased p62 expression in both MAFLD animal models and free fatty acid (FFA)\u2010induced HepG2 cells. Notably, HGT suppressed p\u2010mTOR while increasing p\u2010AMPK levels. Mechanistically, co\u2010treatment with Compound C (an AMPK inhibitor) or 3\u2010MA (an autophagy inhibitor) abolished HGT\u2010induced p\u2010AMPK elevation, LC3B\u2010II\/I upregulation, and lipid reduction. Notably, HGT counteracted MHY1485 (a selective mTOR activator)\u2010induced p\u2010mTOR elevation and lipid accumulation. Collectively, these findings demonstrate that HGT alleviates hepatic lipid deposition by activating autophagy through the AMPK\/mTOR pathway, highlighting its potential as a therapeutic strategy for treating MAFLD.<\/jats:p>","DOI":"10.1002\/cbdv.71338","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T04:52:22Z","timestamp":1778734342000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hu Gan Tang Ameliorates Lipid Deposition of Metabolic\u2010Associated Fatty Liver Disease by Promoting Autophagy Through the AMPK\/mTOR Pathway"],"prefix":"10.1002","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7921-4225","authenticated-orcid":false,"given":"Lihua","family":"Cui","sequence":"first","affiliation":[{"name":"Institute of Integrative Medicine for Acute Abdominal Diseases Tianjin Nankai Hospital Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Li","sequence":"additional","affiliation":[{"name":"Hospital of Integrated Chinese and Western Medicine Tianjin University of Traditional Chinese Medicine  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxing","family":"Fan","sequence":"additional","affiliation":[{"name":"Institute of Integrative Medicine for Acute Abdominal Diseases Tianjin Nankai Hospital Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Du","family":"Shang","sequence":"additional","affiliation":[{"name":"Hospital of Integrated Chinese and Western Medicine Tianjin University of Traditional Chinese Medicine  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Yin","sequence":"additional","affiliation":[{"name":"Hospital of Integrated Chinese and Western Medicine Tianjin University of Traditional Chinese Medicine  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caixia","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Integrative Medicine for Acute Abdominal Diseases Tianjin Nankai Hospital Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2649-2414","authenticated-orcid":false,"given":"Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair  Tianjin China"},{"name":"Hospital of Integrated Chinese and Western Medicine Tianjin University of Traditional Chinese Medicine  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.04.036"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2025.0644"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2022.0398"},{"key":"e_1_2_10_5_1","first-page":"469","article-title":"The Lipid Basis of Cell Death and Autophagy","volume":"20","author":"Zhi L.","year":"2023","journal-title":"Autophagy"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07976"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010nutr\u2010071813\u2010105336"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2128019"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/4825949"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24076437"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.3628"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202101456R"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.12.019"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.1287"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2119824119"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2019.02.005"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201008829\u20103"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.05.001"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chmed.2022.09.006"},{"key":"e_1_2_10_20_1","article-title":"Curcumin Analog CUR5\u20108 Ameliorates Nonalcoholic Fatty Liver Disease in Mice With High\u2010Fat Diet\u2010Induced Obesity","volume":"103","author":"Soo L. 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