{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:21:27Z","timestamp":1781101287445,"version":"3.54.1"},"reference-count":48,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T00:00:00Z","timestamp":1729123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82304642"],"award-info":[{"award-number":["82304642"]}]},{"name":"National Natural Science Foundation of China","award":["82274200"],"award-info":[{"award-number":["82274200"]}]},{"name":"National Natural Science Foundation of China","award":["82074114"],"award-info":[{"award-number":["82074114"]}]},{"name":"National Natural Science Foundation of China","award":["BK20221526"],"award-info":[{"award-number":["BK20221526"]}]},{"name":"National Natural Science Foundation of China","award":["BK20210430"],"award-info":[{"award-number":["BK20210430"]}]},{"name":"National Natural Science Foundation of China","award":["CPU2018GY33"],"award-info":[{"award-number":["CPU2018GY33"]}]},{"name":"Natural Science Foundation of Jiangsu Province","award":["82304642"],"award-info":[{"award-number":["82304642"]}]},{"name":"Natural Science Foundation of Jiangsu Province","award":["82274200"],"award-info":[{"award-number":["82274200"]}]},{"name":"Natural Science Foundation of Jiangsu Province","award":["82074114"],"award-info":[{"award-number":["82074114"]}]},{"name":"Natural Science Foundation of Jiangsu Province","award":["BK20221526"],"award-info":[{"award-number":["BK20221526"]}]},{"name":"Natural Science Foundation of Jiangsu Province","award":["BK20210430"],"award-info":[{"award-number":["BK20210430"]}]},{"name":"Natural Science Foundation of Jiangsu Province","award":["CPU2018GY33"],"award-info":[{"award-number":["CPU2018GY33"]}]},{"name":"\u201cDouble First\u2014Class\u201d University Project","award":["82304642"],"award-info":[{"award-number":["82304642"]}]},{"name":"\u201cDouble First\u2014Class\u201d University Project","award":["82274200"],"award-info":[{"award-number":["82274200"]}]},{"name":"\u201cDouble First\u2014Class\u201d University Project","award":["82074114"],"award-info":[{"award-number":["82074114"]}]},{"name":"\u201cDouble First\u2014Class\u201d University Project","award":["BK20221526"],"award-info":[{"award-number":["BK20221526"]}]},{"name":"\u201cDouble First\u2014Class\u201d University Project","award":["BK20210430"],"award-info":[{"award-number":["BK20210430"]}]},{"name":"\u201cDouble First\u2014Class\u201d University Project","award":["CPU2018GY33"],"award-info":[{"award-number":["CPU2018GY33"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: Altered patterns of bile acids (BAs) are frequently present in liver fibrosis, and BAs function as signaling molecules to initiate inflammatory responses. Silybin meglumine (SLB-M) is widely used in treating various liver diseases including liver fibrosis. However, research on its effects on bile acid (BA) metabolism is limited. This study investigated the therapeutic effects of SLB-M on liver fibrosis and BA metabolism in a CCl4-induced murine model. Methods: A murine liver fibrosis model was induced by CCl4. Fibrosis was evaluated using HE, picrosirius red, and Masson\u2019s trichrome staining. Liver function was assessed by serum and hepatic biochemical markers. Bile acid (BA) metabolism was analyzed using LC-MS\/MS. Bioinformatics analyses, including PPI network, GO, and KEGG pathway analyses, were employed to explore molecular mechanisms. Gene expression alterations in liver tissue were examined via qRT-PCR. Results: SLB-M treatment resulted in significant histological improvements in liver tissue, reducing collagen deposition and restoring liver architecture. Biochemically, SLB-M not only normalized serum liver enzyme levels (ALT, AST, TBA, and GGT) but also mitigated disruptions in both systemic and hepatic BA metabolism by increased unconjugated BAs like cholic acid and chenodeoxycholic acid but decreased conjugated BAs including taurocholic acid and taurodeoxycholic acid, compared to that in CCl4-induced murine model. Notably, SLB-M efficiently improved the imbalance of BA homeostasis in liver caused by CCl4 via activating Farnesoid X receptor. Conclusions: These findings underscore SLB-M decreased inflammatory response, reconstructed BA homeostasis possibly by regulating key pathways, and gene expressions in BA metabolism.<\/jats:p>","DOI":"10.3390\/metabo14100556","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T04:42:15Z","timestamp":1729140135000},"page":"556","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Silybin Meglumine Mitigates CCl4-Induced Liver Fibrosis and Bile Acid Metabolism Alterations"],"prefix":"10.3390","volume":"14","author":[{"given":"Xiaoxin","family":"Liu","sequence":"first","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ninglin","family":"Xia","sequence":"additional","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinwei","family":"Yu","sequence":"additional","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Jin","sequence":"additional","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zifan","family":"Wang","sequence":"additional","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Fan","sequence":"additional","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhao","sequence":"additional","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anqin","family":"Li","sequence":"additional","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0420-0822","authenticated-orcid":false,"given":"Zhenzhou","family":"Jiang","sequence":"additional","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyong","family":"Zhang","sequence":"additional","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"},{"name":"Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1177\/1535370219898141","article-title":"Mechanisms of liver fibrosis and its role in liver cancer","volume":"245","author":"Dhar","year":"2020","journal-title":"Exp. 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