{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T20:34:32Z","timestamp":1778186072003,"version":"3.51.4"},"reference-count":27,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hong Kong Innovation and Technology Commission","award":["ITCPD\/17-9"],"award-info":[{"award-number":["ITCPD\/17-9"]}]},{"name":"the Guangdong Provincial Department of Science and Technology, Guangdong-Hong Kong-Macao Joint Innovation Field Project","award":["2022A0505030020"],"award-info":[{"award-number":["2022A0505030020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Backgrounds: Non-alcoholic fatty liver disease (NAFLD) is a multifaceted metabolic disorder that has become a prominent public health problem worldwide. As a traditional Chinese medicine formula, the ErChen decoction (ECD) possesses significant effects on metabolic syndrome. Methods: To determine whether ECD can relieve lipid accumulation and insulin resistance (IR) in liver cells, NAFLD and IR cell models were established by treating HepG2 cells with free fatty acids and an overdose of insulin, respectively. Bioinformatics and experimental evidence demonstrated that ECD could ameliorate NAFLD by modulating multiple pathways. The optimal combination of the key compounds in ECD was identified by the orthogonal experiment. Results: For lipid homeostasis, ECD suppressed de novo lipogenesis and reduced the cholesterol level by activating the AMPK signaling pathway. Concurrently, ECD enhanced hepatic \u03b2-oxidation by inducing PPAR\u03b1-mediated upregulation of ACOX-1 and CPT-1\u03b1. ECD also resolved hepatic insulin resistance by activating the IRS1-Akt-FoxO1 pathway. The combined treatment with 100 \u03bcM liquiritin (LQ), 200 \u03bcM glycyrrhizic acid (GA) and 200 \u03bcM hesperidin (HEN) exhibited the best effect in reducing TG content in NAFLD model cells. Conclusions: ECD exhibited superior activities in activating the AMPK signaling pathway compared to the optimal compound combination. The comparison between the ECD and its key compounds demonstrated the superior synergistic effects of the herbs in ECD.<\/jats:p>","DOI":"10.3390\/ph18111707","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T10:56:27Z","timestamp":1762858587000},"page":"1707","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The ErChen Decoction and Its Active Compounds Ameliorate Non-Alcoholic Fatty Liver Disease Through Activation of the AMPK Signaling Pathway"],"prefix":"10.3390","volume":"18","author":[{"given":"Ye","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Life Science and State Key Lab for Molecular Neural Science, The Hong Kong University of Science and Technology, Hong Kong 999077, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanting","family":"Liang","sequence":"additional","affiliation":[{"name":"Division of Life Science and State Key Lab for Molecular Neural Science, The Hong Kong University of Science and Technology, Hong Kong 999077, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4383-7666","authenticated-orcid":false,"given":"Man Hei","family":"Cheung","sequence":"additional","affiliation":[{"name":"Division of Life Science and State Key Lab for Molecular Neural Science, The Hong Kong University of Science and Technology, Hong Kong 999077, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinran","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Life Science and State Key Lab for Molecular Neural Science, The Hong Kong University of Science and Technology, Hong Kong 999077, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huimei","family":"Mo","sequence":"additional","affiliation":[{"name":"EnKang Pharmaceuticals (Guangzhou), Ltd., Guangzhou 511455, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiehua","family":"Gan","sequence":"additional","affiliation":[{"name":"EnKang Pharmaceuticals (Guangzhou), Ltd., Guangzhou 511455, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9731-197X","authenticated-orcid":false,"given":"Wei","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Life Science and State Key Lab for Molecular Neural Science, The Hong Kong University of Science and Technology, Hong Kong 999077, China"},{"name":"Guangzhou Bay Area Institute of Biomedicine, Guangdong Lewwin Pharmaceutical Research Institute Co., Ltd., Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research, Guangzhou 510990, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3319-5580","authenticated-orcid":false,"given":"Jianmin","family":"Guo","sequence":"additional","affiliation":[{"name":"Division of Life Science and State Key Lab for Molecular Neural Science, The Hong Kong University of Science and Technology, Hong Kong 999077, China"},{"name":"Guangzhou Bay Area Institute of Biomedicine, Guangdong Lewwin Pharmaceutical Research Institute Co., Ltd., Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research, Guangzhou 510990, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2180-0931","authenticated-orcid":false,"given":"Chun","family":"Liang","sequence":"additional","affiliation":[{"name":"Division of Life Science and State Key Lab for Molecular Neural Science, The Hong Kong University of Science and Technology, Hong Kong 999077, China"},{"name":"EnKang Pharmaceuticals (Guangzhou), Ltd., Guangzhou 511455, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Factors that predict the progression of non-alcoholic fatty liver disease (NAFLD)","volume":"13","author":"Parameswaran","year":"2021","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1210\/endrev\/bnz009","article-title":"Nonalcoholic fatty liver disease in adults: Current concepts in etiology, outcomes, and management","volume":"41","author":"Marjot","year":"2020","journal-title":"Endocr. 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