Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2020.008
Gentiopicroside Ameliorates the Progression from Hepatic Steatosis to Fibrosis Induced by Chronic Alcohol Intake
Hong-Xu Yang1,†, Yue Shang1,†, Quan Jin1,†, Yan-Ling Wu1, Jian Liu1, Chun-Ying Qiao1, Zi-Ying Zhan1, Huan Ye1, Ji-Xing Nan1,2,* and Li-Hua Lian1,*
1Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji 133002, China
2Clinical Research Center, Yanbian University Hospital, Yanji 133002, China
E-mail: lhlian@ybu.edu.cn (Lian LH), jxnan@ybu.edu.cn (Nan JX)
Tel: +86-433-2435072 (Lian LH), +86-433-2435061 (Nan JX)
Fax: +86-433-2435072 (Lian LH), +86-433-2435072 (Nan JX)
The first three authors contributed equally to this work.
Received: January 23, 2020; Revised: February 11, 2020; Accepted: March 2, 2020; Published online: April 6, 2020.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
In current study, we aimed to investigate whether the gentiopicroside (GPS) derived from Gentiana manshurica Kitagawa could block the progression of alcoholic hepatic steatosis to fibrosis induced by chronic ethanol intake. C57BL/6 mice were fed an ethanol- containing Lieber-DeCarli diet for 4 weeks. LX-2 human hepatic stellate cells were treated with GPS 1 h prior to transforming growth factor-β (TGF-β) stimulation, and murine hepatocyte AML12 cells were pretreated by GPS 1 h prior to ethanol treatment. GPS inhibited the expression of type I collagen (collagen I), α-smooth muscle actin (α-SMA) and tissue inhibitor of metal protease 1 (TIMP-1) in ethanol-fed mouse livers with mild fibrosis. In addition, the imbalanced lipid metabolism induced by chronic ethanolfeeding was ameliorated by GPS pretreatment, characterized by the modulation of lipid accumulation. Consistently, GPS inhibited the expression of collagen I and α-SMA in LX-2 cells stimulated by TGF-β. Inhibition of lipid synthesis and promotion of oxidation by GPS were also confirmed in ethanol-treated AML12 cells. GPS could prevent hepatic steatosis advancing to the inception of a mild fibrosis caused by chronic alcohol exposure, suggesting GPS might be a promising therapy for targeting the early stage of alcoholic liver disease.
Keywords: Gentiopicroside, Hepatic fibrosis, Hepatic steatosis, Chronic alcohol intake


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