{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T04:56:18Z","timestamp":1790571378630,"version":"4.1.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"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>Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation and metabolic dysregulation, while effective therapeutic options remain limited. Hepatoprotective Formula 919 (HF919), a traditional Chinese herbal formulation, has shown hepatoprotective effects, but its mechanisms in NAFLD remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the effects of HF919 on hepatic steatosis and metabolic disturbance in NAFLD and the possible involvement of AMPK-associated metabolic regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Candidate absorbed constituents of HF919 were characterized by UPLC-HRMS and prioritized by\n                      <jats:italic>in silico<\/jats:italic>\n                      screening based on predicted oral bioavailability and drug-likeness. Network pharmacology, public human liver transcriptomic analyses, and molecular docking were integrated to examine disease-relevant candidate targets and pathways. The\n                      <jats:italic>in vivo<\/jats:italic>\n                      effects of HF919 were evaluated in a high-fat diet-induced NAFLD rat model using histological, biochemical, molecular, and immunohistochemical analyses. Fecal short-chain fatty acid (SCFA) profiling was additionally performed as an exploratory metabolic analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HF919 alleviated hepatic steatosis, reduced hepatic lipid accumulation, and improved serum and hepatic lipid-related indices in HFD-induced NAFLD rats. HF919 treatment increased hepatic p-AMPK abundance and\n                      <jats:italic>Ppara<\/jats:italic>\n                      expression and reduced the expression of\n                      <jats:italic>Tlr4, Nfkb2,<\/jats:italic>\n                      and\n                      <jats:italic>Tgfb1<\/jats:italic>\n                      . Hepatic F4\/80-positive staining was significantly reduced, accompanied by increased expression of the macrophage-associated genes\n                      <jats:italic>Mertk<\/jats:italic>\n                      and\n                      <jats:italic>Arg1<\/jats:italic>\n                      . Public liver transcriptomic analyses showed lower AMPK- and fatty-acid-oxidation-associated transcriptional features in NASH and in more severe histopathological categories, supporting the disease relevance of these metabolic alterations. Integration of HF919-predicted targets with disease-related transcriptomic changes identified metabolic and injury-related candidate pathways, while molecular docking showed favorable predicted docking scores for selected ligand\u2013target pairs. Exploratory SCFA analysis showed shifts in several fecal SCFAs toward the control-associated pattern and associations with selected hepatic metabolic and molecular parameters.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      HF919 ameliorated hepatic steatosis and metabolic abnormalities in HFD-induced NAFLD rats. The accompanying increase in hepatic p-AMPK abundance and\n                      <jats:italic>Ppara<\/jats:italic>\n                      expression, together with disease-context evidence from human liver transcriptomic datasets, supports the possible involvement of AMPK-associated metabolic regulation. Changes in selected injury-related and macrophage-associated markers and fecal SCFA profiles provided additional secondary or exploratory observations. Further mechanistic studies are needed to establish the causal contribution of AMPK signaling to the effects of HF919.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1892654","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T04:29:11Z","timestamp":1790569751000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Hepatoprotective Formula 919 ameliorates hepatic steatosis and metabolic disturbance in NAFLD with involvement of AMPK signaling"],"prefix":"10.3389","volume":"17","author":[{"given":"Manman","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Traditional Chinese Medicine, Jinshan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Future Network Center, Purple Mountain Laboratories","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Jinshan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuemei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Jinshan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Jinshan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiling","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Jinshan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"110286","DOI":"10.1016\/j.biopha.2020.110286","article-title":"Chinese herbal medicine mixture 919 syrup alleviates nonalcoholic fatty liver disease in rats by inhibiting the NF-\u03baB pathway","volume":"128","author":"Chen","year":"2020","journal-title":"Biomed. 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