{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T16:35:14Z","timestamp":1787675714803,"version":"build-2784847793"},"reference-count":57,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004699","name":"Chung Shan Medical University Hospital","doi-asserted-by":"publisher","award":["CSH-2022-C-041"],"award-info":[{"award-number":["CSH-2022-C-041"]}],"id":[{"id":"10.13039\/501100004699","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metabolic dysfunction-associated steatotic liver disease (MASLD) begins with hepatic lipid accumulation and triggers insulin resistance. Hibiscus leaf extract exhibits antioxidant and anti-atherosclerotic activities, and is rich in (\u2212)-epicatechin gallate (ECG). Despite ECG\u2019s well-known pharmacological activities and its total antioxidant capacity being stronger than that of other catechins, its regulatory effects on MASLD have not been fully described previously. Therefore, this study attempted to evaluate the anti-MASLD potential of ECG isolated from Hibiscus leaves on abnormal lipid and glucose metabolism in hepatocytes. First, oleic acid (OA) was used as an experimental model to induce lipid dysmetabolism in human primary hepatocytes. Treatment with ECG can significantly (p &lt; 0.05) reduce the OA-induced cellular lipid accumulation. Nile red staining revealed, compared to the OA group, the inhibition percentages of 29, 61, and 82% at the tested doses of ECG, respectively. The beneficial effects of ECG were associated with the downregulation of SREBPs\/HMGCR and upregulation of PPAR\u03b1\/CPT1 through targeting AMPK. Also, ECG at 0.4 \u00b5M produced a significant (p &lt; 0.01) decrease in oxidative stress by 83%, and a marked (p &lt; 0.05) increase in glycogen synthesis by 145% on the OA-exposed hepatocytes with insulin signaling blockade. Mechanistic assays indicated lipid and glucose metabolic homeostasis of ECG might be mediated via regulation of lipogenesis, fatty acid \u03b2-oxidation, and insulin resistance, as confirmed by an AMPK inhibitor. These results suggest ECG is a dual modulator of lipid and carbohydrate dysmetabolism in hepatocytes.<\/jats:p>","DOI":"10.3390\/ijms26157612","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T15:09:53Z","timestamp":1754492993000},"page":"7612","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["AMPK-Targeting Effects of (\u2212)-Epicatechin Gallate from Hibiscus\u00a0sabdariffa Linne Leaves on Dual Modulation of Hepatic Lipid Accumulation and Glycogen Synthesis in an In Vitro Oleic Acid Model"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0021-5709","authenticated-orcid":false,"given":"Hui-Hsuan","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung City 40201, Taiwan"},{"name":"Clinical Laboratory, Chung Shan Medical University Hospital, Taichung City 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Tzu","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung City 40201, Taiwan"},{"name":"Clinical Laboratory, Chung Shan Medical University Hospital, Taichung City 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hsuan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Chung Shan Medical University, Taichung City 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Shih","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung City 40201, Taiwan"},{"name":"Clinical Laboratory, Chung Shan Medical University Hospital, Taichung City 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5756-5959","authenticated-orcid":false,"given":"Jing-Hsien","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Chung Shan Medical University, Taichung City 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms of NAFLD Development and therapeutic strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat. 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