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Active saponin constituents isolated from Gynostemma pentaphyllum were found to possess a protective effect in liver diseases. Here, we obtained a naturally abundant gypenoside, XLVI, and evaluated its liver protection activity in both animal and cellular models. The results showed that it ameliorated acute and chronic liver injuries and lightened the process of fibrogenesis in vivo. XLVI can inhibit TGF-\u03b2-induced activation of hepatic stellate cells and ECM deposition in vitro. The underlying mechanism study verified that it upregulated the protein expression of protein phosphatase 2C alpha and strengthened the vitality of the phosphatase together with a PP2C\u03b1 agonist gypenoside NPLC0393. These results shed new light on the molecular mechanisms and the potential therapeutic function of the traditional herb Gynostemma pentaphyllum in the treatment of liver fibrosis.<\/jats:p>","DOI":"10.3390\/molecules28145448","type":"journal-article","created":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T00:56:47Z","timestamp":1689555407000},"page":"5448","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Gypenosides Synergistically Reduce the Extracellular Matrix of Hepatic Stellate Cells and Ameliorate Hepatic Fibrosis in Mice"],"prefix":"10.3390","volume":"28","author":[{"given":"Han","family":"Li","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanghang","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiping","family":"Yang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingzhen","family":"Xue","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Lv","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Liu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihong","family":"Hu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1106-1904","authenticated-orcid":false,"given":"Xiachang","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"Fujian Province Key Laboratory for the Development of Bioactive Material from Marine Algae, College of Oceanology and Food Science, Quanzhou Normal University, Quanzhou 362000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41575-020-00372-7","article-title":"Molecular and cellular mechanisms of liver fibrosis and its regression","volume":"18","author":"Kisseleva","year":"2021","journal-title":"Nat. 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