{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:25:24Z","timestamp":1791559524915,"version":"4.3.4"},"reference-count":64,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Sichuan Administration of Traditional Chinese Medicine","award":["2023MS498"],"award-info":[{"award-number":["2023MS498"]}]},{"name":"The Sichuan Administration of Traditional Chinese Medicine","award":["2022JDKY0013"],"award-info":[{"award-number":["2022JDKY0013"]}]},{"DOI":"10.13039\/100012542","name":"Fundamental Research Funds for Sichuan Provincial Scientific Research Institutes","doi-asserted-by":"publisher","award":["2023MS498"],"award-info":[{"award-number":["2023MS498"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012542","name":"Fundamental Research Funds for Sichuan Provincial Scientific Research Institutes","doi-asserted-by":"publisher","award":["2022JDKY0013"],"award-info":[{"award-number":["2022JDKY0013"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Metabolism-associated fatty liver disease (MAFLD), a growing health problem worldwide, is one of the major risks for the development of cirrhosis and liver cancer. Oral administration of nobiletin (NOB), a natural citrus flavonoid, modulates the gut microbes and their metabolites in mice. In the present study, we established a mouse model of MAFLD by subjecting mice to a high-fat diet (HFD) for 12 weeks. Throughout this timeframe, NOB was administered to investigate its potential benefits on gut microbial balance and bile acid (BA) metabolism using various techniques, including 16S rRNA sequencing, targeted metabolomics of BA, and biological assays. NOB effectively slowed the progression of MAFLD by reducing serum lipid levels, blood glucose levels, LPS levels, and hepatic IL-1\u03b2 and TNF-\u03b1 levels. Furthermore, NOB reinstated diversity within the gut microbial community, increasing the population of bacteria that produce bile salt hydrolase (BSH) to enhance BA excretion. By exploring further, we found NOB downregulated hepatic expression of the farnesoid X receptor (FXR) and its associated small heterodimer partner (SHP), and it increased the expression of downstream enzymes, including cholesterol 7\u03b1-hydroxylase (CYP7A1) and cytochrome P450 27A1 (CYP27A1). This acceleration in cholesterol conversion within the liver contributes to mitigating MAFLD. The present findings underscore the significant role of NOB in regulating gut microbial balance and BA metabolism, revealing that long-term intake of NOB plays beneficial roles in the prevention or intervention of MAFLD.<\/jats:p>","DOI":"10.3390\/molecules29050976","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T07:33:56Z","timestamp":1708673636000},"page":"976","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Involvement of Bile Acid Metabolism and Gut Microbiota in the Amelioration of Experimental Metabolism-Associated Fatty Liver Disease by Nobiletin"],"prefix":"10.3390","volume":"29","author":[{"given":"Hongling","family":"Xu","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingming","family":"Yuan","sequence":"additional","affiliation":[{"name":"Laboratory Animal Center Affiliate from Research Office, Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailin","family":"Niu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory Animal Center Affiliate from Research Office, Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maoyuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"},{"name":"Laboratory Animal Center Affiliate from Research Office, Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Laboratory Animal Center Affiliate from Research Office, Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1053\/j.gastro.2019.11.312","article-title":"MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease","volume":"158","author":"Eslam","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1097\/CM9.0000000000002089","article-title":"From MAFLD to Hepatocellular Carcinoma and Everything in Between","volume":"135","author":"Bae","year":"2022","journal-title":"Chin. 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