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oai:figshare.com:article/34008099 2026-09-28T04:27:58Z category_19 portal_316 item_type_3 month_year_09_2026

Supplementary file 1_Hepatoprotective Formula 919 ameliorates hepatic steatosis and metabolic disturbance in NAFLD with involvement of AMPK signaling.docx Manman Chen (4347943) Zheng Xu (162992) Yu Chen (29959) Yuemei Xu (5844911) Lan Zhang (90951) Yiling Zhao (9374190) Pengfei Gao (1292217) Pharmacology AMPK signaling hepatic steatosis Hepatoprotective Formula 919 lipid metabolism metabolic disturbance NAFLD Background<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.</p>Objective<p>To evaluate the effects of HF919 on hepatic steatosis and metabolic disturbance in NAFLD and the possible involvement of AMPK-associated metabolic regulation.</p>Methods<p>Candidate absorbed constituents of HF919 were characterized by UPLC-HRMS and prioritized by in silico 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 in vivo 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.</p>Results<p>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 Ppara expression and reduced the expression of Tlr4, Nfkb2, and Tgfb1. Hepatic F4/80-positive staining was significantly reduced, accompanied by increased expression of the macrophage-associated genes Mertk and Arg1. 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–target pairs. Exploratory SCFA analysis showed shifts in several fecal SCFAs toward the control-associated pattern and associations with selected hepatic metabolic and molecular parameters.</p>Conclusion<p>HF919 ameliorated hepatic steatosis and metabolic abnormalities in HFD-induced NAFLD rats. The accompanying increase in hepatic p-AMPK abundance and Ppara 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.</p> 2026-09-28T04:27:58Z Dataset Dataset 10.3389/fphar.2026.1892654.s003 https://figshare.com/articles/dataset/Supplementary_file_1_Hepatoprotective_Formula_919_ameliorates_hepatic_steatosis_and_metabolic_disturbance_in_NAFLD_with_involvement_of_AMPK_signaling_docx/34008099 CC BY 4.0