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However, its efficacy in preventing high fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and its relationship with gut microbiota and hepatic inflammation remain unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Purpose<\/jats:title>\n            <jats:p>The study aims to investigate whether QKL can prevent HFD-induced NAFLD, focusing on the mechanistic role of gut microbiota, microbial metabolites, and hepatic inflammation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>QKL was subjected to extraction and chemical profiling to identify its active compounds. In vivo studies were conducted in HFD-fed mice to assess the effects of QKL on hepatic lipid accumulation, inflammation, gut microbiota composition, SCFAs production, intestinal permeability, body weight, and fat mass.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Chemical analysis revealed that the major components of QKL are gallic acid, corilagin, and chebulagic acid. QKL administration (12.33 and 24.66\u00a0mL\/kg) for 8\u00a0weeks significantly reduced hepatic steatosis, serum lipid profiles (TG, LDL-C), and body weight in high-fat diet-induced NAFLD mice, while improving glucose tolerance and intestinal barrier integrity. Gut microbiota analysis revealed QKL enriched beneficial taxa (e.g., <jats:italic>Akkermansia<\/jats:italic>, <jats:italic>Bacteroides<\/jats:italic>) and suppressed pathobionts (e.g., <jats:italic>Lachnospiraceae NK4A136_group<\/jats:italic>), effects replicated through faecal microbiota transplantation from QKL-treated donors. QKL upregulated intestinal gene <jats:italic>GPR41\/43<\/jats:italic> and hepatic protein GPR135 expression, enhanced SCFAs production (acetic, propionic, and butyric acids), and activated AMPK\/ACC1 signaling to suppress lipogenesis and promote lipid oxidation. Untargeted metabolomics demonstrated QKL restored hepatic fatty acid metabolism by reducing palmitic acid and arachidonic acid accumulation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>These findings established QKL as a microbiota-modulating therapeutic agent for NAFLD through SCFA-AMPK\/ACC1 axis activation, providing a foundation for developing QKL-based treatments.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphical Abstract<\/jats:title>\n          <\/jats:sec>","DOI":"10.1186\/s13020-025-01237-4","type":"journal-article","created":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T16:02:55Z","timestamp":1760889775000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Qing-Kai-Ling oral liquid alleviates non-alcoholic fatty liver disease via remodeling gut microbiota and activating AMPK\/ACC1 axis"],"prefix":"10.1186","volume":"20","author":[{"given":"Kaiwei","family":"Cai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biyan","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenglian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiongfeng","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,19]]},"reference":[{"issue":"2","key":"1237_CR1","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/s41575-020-00406-0","volume":"18","author":"MF Abdelmalek","year":"2021","unstructured":"Abdelmalek MF. 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