{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T03:53:41Z","timestamp":1789098821895,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:00:00Z","timestamp":1689724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Project of the Traditional Chinese Medicine of Hubei Provincial Health Commission","award":["ZY2021Z006"],"award-info":[{"award-number":["ZY2021Z006"]}]},{"name":"Research Project of the Traditional Chinese Medicine of Hubei Provincial Health Commission","award":["Q20202006"],"award-info":[{"award-number":["Q20202006"]}]},{"name":"Research Project of the Traditional Chinese Medicine of Hubei Provincial Health Commission","award":["2020CFA024"],"award-info":[{"award-number":["2020CFA024"]}]},{"name":"Scientific Research Plan of Hubei Provincial Department of Education","award":["ZY2021Z006"],"award-info":[{"award-number":["ZY2021Z006"]}]},{"name":"Scientific Research Plan of Hubei Provincial Department of Education","award":["Q20202006"],"award-info":[{"award-number":["Q20202006"]}]},{"name":"Scientific Research Plan of Hubei Provincial Department of Education","award":["2020CFA024"],"award-info":[{"award-number":["2020CFA024"]}]},{"name":"Natural Science Foundation of Hubei Province","award":["ZY2021Z006"],"award-info":[{"award-number":["ZY2021Z006"]}]},{"name":"Natural Science Foundation of Hubei Province","award":["Q20202006"],"award-info":[{"award-number":["Q20202006"]}]},{"name":"Natural Science Foundation of Hubei Province","award":["2020CFA024"],"award-info":[{"award-number":["2020CFA024"]}]},{"name":"Young Top-notch Talent Cultivation Program of Hubei Province","award":["ZY2021Z006"],"award-info":[{"award-number":["ZY2021Z006"]}]},{"name":"Young Top-notch Talent Cultivation Program of Hubei Province","award":["Q20202006"],"award-info":[{"award-number":["Q20202006"]}]},{"name":"Young Top-notch Talent Cultivation Program of Hubei Province","award":["2020CFA024"],"award-info":[{"award-number":["2020CFA024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Liver fibrosis is one of the leading causes of hepatic sclerosis and hepatocellular carcinoma worldwide. However, the complex pathophysiological mechanisms of liver fibrosis are unknown, and no specific drugs are available to treat liver fibrosis. Atractylenolide III (ATL III) is a natural compound isolated from the plant Atractylodes lancea (Thunb.) DC. that possesses antioxidant properties and the ability to inhibit inflammatory responses. In this study, cholestatic hepatic fibrosis was induced in mice using a bile duct ligation (BDL) model and treated with 10 mg\/kg and 50 mg\/kg of ATL III via gavage for 14 days. ATL III significantly reduced the liver index, lowered serum ALT and AST levels, and reduced liver injury in bile-duct-ligated mice. In addition, ATL III significantly attenuated histopathological changes and reduced collagen deposition. ATL III reduced the expression of fibrosis-related genes \u03b1-smooth muscle actin (\u03b1-SMA), Collagen I (col1a1), Collagen IV (col4a2), and fibrosis-related proteins \u03b1-SMA and col1a1 in liver tissue. Using RNA sequencing (RNA-seq) to screen molecular targets and pathways, ATL III was found to affect the PI3K\/AKT singling pathway by inhibiting the phosphorylation of PI3K and AKT, thereby ameliorating BDL-induced liver fibrosis. Gas chromatography\u2013mass spectrometry (GC-MS) was used to evaluate the effect of ATL III on liver metabolites in BDL mice. ATL III further affected glutamine metabolism by down-regulating the activity of glutamine (GLS1) and glutamine metabolism. ATL III further affected glutamine metabolism by down-regulating the activity of glutaminase (GLS1), as well as glutamine metabolism. Therefore, we conclude that ATL III attenuates liver fibrosis by inhibiting the PI3K\/AKT pathway and glutamine metabolism, suggesting that ATL III is a potential drug candidate for treating liver fibrosis.<\/jats:p>","DOI":"10.3390\/molecules28145504","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T21:22:58Z","timestamp":1689801778000},"page":"5504","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Atractylenolide III Ameliorates Bile Duct Ligation-Induced Liver Fibrosis by Inhibiting the PI3K\/AKT Pathway and Regulating Glutamine Metabolism"],"prefix":"10.3390","volume":"28","author":[{"given":"Yan","family":"Wang","sequence":"first","affiliation":[{"name":"College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Shi","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyuan","family":"Tu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China"},{"name":"Center for Hubei TCM Processing Technology Engineering, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Ke","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niping","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[{"name":"Hubei Institute for Drug Control, NMPA Key Laboratory of Quality Control of Chinese Medicine, Hubei Engineering Research Center for Drug Quality Control, Wuhan 430075, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanju","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China"},{"name":"Center for Hubei TCM Processing Technology Engineering, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongshi","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China"},{"name":"Center for Hubei TCM Processing Technology Engineering, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104720","DOI":"10.1016\/j.phrs.2020.104720","article-title":"Intercellular crosstalk of hepatic stellate cells in liver fibrosis: New insights into therapy","volume":"155","author":"Cai","year":"2020","journal-title":"Pharmacol. 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