{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T08:09:04Z","timestamp":1793174944725,"version":"4.5.0"},"reference-count":36,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011789","name":"Jilin Province Science and Technology Department","doi-asserted-by":"crossref","award":["YDZJ202201ZYTS457"],"award-info":[{"award-number":["YDZJ202201ZYTS457"]}],"id":[{"id":"10.13039\/501100011789","id-type":"DOI","asserted-by":"crossref"}]},{"award":["YDZJ202201ZYTS457"],"award-info":[{"award-number":["YDZJ202201ZYTS457"]}],"id":[{"id":"https:\/\/ror.org\/049x38272","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cyanidin-3-O-Glucoside (C3G) is the primary anthocyanin-active component in bilberry, exhibiting various pharmacological activities such as antioxidant, anti-inflammatory, and lipid metabolism-regulating effects. To address the clinical need for non-alcoholic fatty liver disease (NAFLD) prevention and treatment, this study aimed to investigate the ameliorative effects of C3G on NAFLD pathology and elucidate its molecular mechanisms of protection via the AMPK pathway. After a one-week acclimatization period, 20 six-week-old SPF mice were randomly divided into four groups: normal diet control (NCD), high-fat diet model (HFD), HFD + L-C3G (100 mg\/kg\/day), and HFD + H-C3G (200 mg\/kg\/day). Except for the NCD group, the remaining groups were fed a 60% high-fat diet for four weeks to establish an early-stage NAFLD model, with successful model construction verified by weight and liver weight gain. From the fifth week onward, C3G groups received daily administration for four consecutive weeks, while control groups were given an equal volume of distilled water. Liver function, lipid metabolism, oxidative stress, and inflammatory levels were assessed using ELISA, H&amp;E staining, and other methods. The results showed that C3G restored liver function in NAFLD mice, improved lipid metabolism disorders, reduced oxidative stress and inflammatory responses, and alleviated liver pathological damage. Mechanistic studies revealed that C3G regulated the expression of mRNA and proteins related to the AMPK\/SIRT1\/NF-\u03baB signaling pathway, activating the pathway by upregulating AMPK and its upstream regulators while inhibiting NF-\u03baB-mediated inflammatory responses. This study confirmed that C3G can ameliorate high-fat diet-induced NAFLD lesions by activating the AMPK\/SIRT1\/NF-\u03baB pathway, providing a potential intervention strategy for NAFLD prevention and treatment.<\/jats:p>","DOI":"10.3390\/ijms27114698","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T01:45:08Z","timestamp":1779673508000},"page":"4698","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cyanidin-3-O-Glucoside Alleviates Hepatic Steatosis and Inflammation in High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Mice via the AMPK\/SIRT1\/NF-\u03baB Pathway"],"prefix":"10.3390","volume":"27","author":[{"given":"Xiping","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Biotechnology, College of Life Sciences, Jilin Normal University, Siping 136000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenya","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Life Sciences, Jilin Normal University, Siping 136000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Life Sciences, Jilin Normal University, Siping 136000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jichun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Life Sciences, Jilin Normal University, Siping 136000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Life Sciences, Jilin Normal University, Siping 136000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxi","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Life Sciences, Jilin Normal University, Siping 136000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Su","sequence":"additional","affiliation":[{"name":"Development and Utilization of Wild Plant Resources in Changbai Mountain, Boda College, Jilin Normal University, Siping 136000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxi","family":"Shen","sequence":"additional","affiliation":[{"name":"Development and Utilization of Wild Plant Resources in Changbai Mountain, Boda College, Jilin Normal University, Siping 136000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2685-2722","authenticated-orcid":false,"given":"Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Life Sciences, Jilin Normal University, Siping 136000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1055\/s-0028-1091980","article-title":"Molecular mechanisms of lipotoxicity in nonalcoholic fatty liver disease","volume":"28","author":"Malhi","year":"2008","journal-title":"Semin. Liver Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.metabol.2016.02.014","article-title":"Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease","volume":"65","author":"Mota","year":"2016","journal-title":"Metabolism"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1053\/j.gastro.2020.04.013","article-title":"Nonalcoholic Fatty Liver Disease in 2020","volume":"158","author":"Maher","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/hepr.14008","article-title":"Advancements in metabolic-associated steatotic liver disease research: Diagnostics, small molecule developments, and future directions","volume":"54","author":"Eeda","year":"2024","journal-title":"Hepatol. Res."},{"key":"ref_5","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. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Nassir, F. (2022). NAFLD: Mechanisms, Treatments, and Biomarkers. Biomolecules, 12.","DOI":"10.3390\/biom12060824"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Fang, C., Pan, J., Qu, N., Lei, Y., Han, J., Zhang, J., and Han, D. (2022). The AMPK pathway in fatty liver disease. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.970292"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3892\/mmr.2022.12922","article-title":"Role of the AMPK\/SIRT1 pathway in non-alcoholic fatty liver disease (Review)","volume":"27","author":"Anggreini","year":"2023","journal-title":"Mol. Med. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"154241","DOI":"10.1016\/j.phymed.2022.154241","article-title":"Kinsenoside alleviates inflammation and fibrosis in experimental NASH mice by suppressing the NF-\u03baB\/NLRP3 signaling pathway","volume":"104","author":"Deng","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3333","DOI":"10.1002\/jsfa.8837","article-title":"Blue honeysuckle (Lonicera caerulea subsp. edulis (Turcz. ex Herder) Hult\u00e9n.) berries and changes in their ingredients across different locations","volume":"98","author":"Senica","year":"2018","journal-title":"J. Sci. Food Agric."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Go\u0142ba, M., Sok\u00f3\u0142-\u0141\u0119towska, A., and Kucharska, A.Z. (2020). Health Properties and Composition of Honeysuckle Berry Lonicera caerulea L. An Update on Recent Studies. Molecules, 25.","DOI":"10.3390\/molecules25030749"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Dayar, E., Cebova, M., Lietava, J., Panghyova, E., and Pechanova, O. (2021). Antioxidant Effect of Lonicera caerulea L. in the Cardiovascular System of Obese Zucker Rats. Antioxidants, 10.","DOI":"10.3390\/antiox10081199"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"146","DOI":"10.3746\/pnf.2024.29.2.146","article-title":"Effects of Haskap (Lonicera caerulea L.) Extracts against Oxidative Stress and Inflammation in RAW 264.7 Cells","volume":"29","author":"Li","year":"2024","journal-title":"Prev. Nutr. Food Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Piekarska, J., Szczypka, M., Gorczykowski, M., Sok\u00f3\u0142-\u0141\u0119towska, A., and Kucharska, A.Z. (2022). Evaluation of Immunotropic Activity of Iridoid-Anthocyanin Extract of Honeysuckle Berries (Lonicera caerulea L.) in the Course of Experimental Trichinellosis in Mice. Molecules, 27.","DOI":"10.3390\/molecules27061949"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"108090","DOI":"10.1016\/j.plaphy.2023.108090","article-title":"Critical review on anthocyanins in blue honeysuckle (Lonicera caerulea L.) and their function","volume":"204","author":"Guo","year":"2023","journal-title":"Plant Physiol. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1039\/C6FO00203J","article-title":"Blue honeysuckle fruit (Lonicera caerulea L.) from eastern Russia: Phenolic composition, nutritional value and biological activities of its polar extracts","volume":"7","author":"Caprioli","year":"2016","journal-title":"Food Funct."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Raudon\u0117, L., Liaudanskas, M., Vilkickyt\u0117, G., Kviklys, D., \u017dvikas, V., Vi\u0161kelis, J., and Vi\u0161kelis, P. (2021). Phenolic Profiles, Antioxidant Activity and Phenotypic Characterization of Lonicera caerulea L. Berries, Cultivated in Lithuania. Antioxidants, 10.","DOI":"10.3390\/antiox10010115"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"167259","DOI":"10.1016\/j.bbadis.2024.167259","article-title":"Cyanidin-3-O-glucoside alleviates ethanol-induced liver injury by promoting mitophagy in a Gao-binge mouse model of alcohol-associated liver disease","volume":"1870","author":"He","year":"2024","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mattioli, R., Francioso, A., Mosca, L., and Silva, P. (2020). Anthocyanins: A Comprehensive Review of Their Chemical Properties and Health Effects on Cardiovascular and Neurodegenerative Diseases. Molecules, 25.","DOI":"10.3390\/molecules25173809"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1002\/ptr.5642","article-title":"Chemistry, Pharmacology and Health Benefits of Anthocyanins","volume":"30","author":"Smeriglio","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1111\/1750-3841.16125","article-title":"Cyanidin-3-O-glucoside, cyanidin, and oxidation products of cyanidin protect neuronal function through alleviating inflammation and oxidative damage","volume":"87","author":"Zhu","year":"2022","journal-title":"J. Food Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease\u2014Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.freeradbiomed.2020.08.006","article-title":"Cyanidin-3-O-\u03b2-glucoside inactivates NLRP3 inflammasome and alleviates alcoholic steatohepatitis via SirT1\/NF-\u03baB signaling pathway","volume":"160","author":"Zhou","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1080\/10408398.2021.1966381","article-title":"Cyanidin-3-O-glucoside and its phenolic metabolites ameliorate intestinal diseases via modulating intestinal mucosal immune system: Potential mechanisms and therapeutic strategies","volume":"63","author":"Cheng","year":"2023","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1016\/j.metabol.2015.05.002","article-title":"Niacin inhibits fat accumulation, oxidative stress, and inflammatory cytokine IL-8 in cultured hepatocytes: Impact on non-alcoholic fatty liver disease","volume":"64","author":"Ganji","year":"2015","journal-title":"Metabolism"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"116848","DOI":"10.1016\/j.jep.2023.116848","article-title":"Zanthoxylum bungeanum amides ameliorates nonalcoholic fatty liver via regulating gut microbiota and activating AMPK\/Nrf2 signaling","volume":"318","author":"Peng","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/biof.5520130122","article-title":"The role of anthocyanins as an antioxidant under oxidative stress in rats","volume":"13","author":"Tsuda","year":"2001","journal-title":"BioFactors"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8391","DOI":"10.1038\/s41467-023-44242-7","article-title":"Cdo1-Camkk2-AMPK axis confers the protective effects of exercise against NAFLD in mice","volume":"14","author":"Chen","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.molcel.2017.05.032","article-title":"AMPK: Mechanisms of Cellular Energy Sensing and Restoration of Metabolic Balance","volume":"66","author":"Garcia","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"852","DOI":"10.7150\/ijbs.19370","article-title":"Emerging roles of SIRT1 in fatty liver diseases","volume":"13","author":"Ding","year":"2017","journal-title":"Int. J. Biol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1016\/j.bbapap.2009.11.021","article-title":"Sirtuins regulate key aspects of lipid metabolism","volume":"1804","author":"Lomb","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"E751","DOI":"10.1152\/ajpendo.00745.2009","article-title":"AMPK and SIRT1: A long-standing partnership?","volume":"298","author":"Ruderman","year":"2010","journal-title":"Am. J. Physiol.\u2014Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Park, M., Yoo, J.H., Lee, Y.S., and Lee, H.J. (2019). Lonicera caerulea Extract Attenuates Non-Alcoholic Fatty Liver Disease in Free Fatty Acid-Induced HepG2 Hepatocytes and in High Fat Diet-Fed Mice. Nutrients, 11.","DOI":"10.3390\/nu11030494"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s10020-023-00642-5","article-title":"Cyanidin-3-glucoside inhibits ferroptosis in renal tubular cells after ischemia\/reperfusion injury via the AMPK pathway","volume":"29","author":"Du","year":"2023","journal-title":"Mol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Spooner, M.H., Garcia-Jaramillo, M., Apperson, K.D., L\u00f6hr, C.V., and Jump, D.B. (2023). Time course of western diet (WD) induced nonalcoholic steatohepatitis (NASH) in female and male Ldlr\u2212\/\u2212 mice. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0292432"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1111\/ijd.13321","article-title":"Expression analysis of activated protein kinase C gene (LACK1) in antimony sensitive and resistant Leishmania tropica clinical isolates using real-time RT-PCR","volume":"55","author":"Hajjaran","year":"2016","journal-title":"Int. J. Dermatol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4698\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T04:23:02Z","timestamp":1780460582000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4698"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,23]]},"references-count":36,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27114698"],"URL":"https:\/\/doi.org\/10.3390\/ijms27114698","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,23]]}}}