Gypenosides Synergistically Reduce the Extracellular Matrix of Hepatic Stellate Cells and Ameliorate Hepatic Fibrosis in Mice

Liver fibrosis resulting from chronic liver damage is becoming one of the major threats to health worldwide. Active saponin constituents isolated from <i>Gynostemma pentaphyllum</i> were found to possess a protective effect in liver diseases. Here, we obtained a naturally abundant gypeno...

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Main Authors: Han Li, Hanghang Wang, Aiping Yang, Mingzhen Xue, Junyang Wang, Qi Lv, Jian Liu, Lihong Hu, Yinan Zhang, Xiachang Wang
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/28/14/5448
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author Han Li
Hanghang Wang
Aiping Yang
Mingzhen Xue
Junyang Wang
Qi Lv
Jian Liu
Lihong Hu
Yinan Zhang
Xiachang Wang
author_facet Han Li
Hanghang Wang
Aiping Yang
Mingzhen Xue
Junyang Wang
Qi Lv
Jian Liu
Lihong Hu
Yinan Zhang
Xiachang Wang
author_sort Han Li
collection DOAJ
description Liver fibrosis resulting from chronic liver damage is becoming one of the major threats to health worldwide. Active saponin constituents isolated from <i>Gynostemma pentaphyllum</i> 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-β-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 PP2Cα agonist gypenoside NPLC0393. These results shed new light on the molecular mechanisms and the potential therapeutic function of the traditional herb <i>Gynostemma pentaphyllum</i> in the treatment of liver fibrosis.
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spelling doaj.art-d2fc395265354c0caff9e0a4721ae8ee2023-11-18T20:42:17ZengMDPI AGMolecules1420-30492023-07-012814544810.3390/molecules28145448Gypenosides Synergistically Reduce the Extracellular Matrix of Hepatic Stellate Cells and Ameliorate Hepatic Fibrosis in MiceHan Li0Hanghang Wang1Aiping Yang2Mingzhen Xue3Junyang Wang4Qi Lv5Jian Liu6Lihong Hu7Yinan Zhang8Xiachang Wang9Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaLiver fibrosis resulting from chronic liver damage is becoming one of the major threats to health worldwide. Active saponin constituents isolated from <i>Gynostemma pentaphyllum</i> 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-β-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 PP2Cα agonist gypenoside NPLC0393. These results shed new light on the molecular mechanisms and the potential therapeutic function of the traditional herb <i>Gynostemma pentaphyllum</i> in the treatment of liver fibrosis.https://www.mdpi.com/1420-3049/28/14/5448gypenosideliver fibrosisPP2Cαextracellular matrixsynergistic effect
spellingShingle Han Li
Hanghang Wang
Aiping Yang
Mingzhen Xue
Junyang Wang
Qi Lv
Jian Liu
Lihong Hu
Yinan Zhang
Xiachang Wang
Gypenosides Synergistically Reduce the Extracellular Matrix of Hepatic Stellate Cells and Ameliorate Hepatic Fibrosis in Mice
Molecules
gypenoside
liver fibrosis
PP2Cα
extracellular matrix
synergistic effect
title Gypenosides Synergistically Reduce the Extracellular Matrix of Hepatic Stellate Cells and Ameliorate Hepatic Fibrosis in Mice
title_full Gypenosides Synergistically Reduce the Extracellular Matrix of Hepatic Stellate Cells and Ameliorate Hepatic Fibrosis in Mice
title_fullStr Gypenosides Synergistically Reduce the Extracellular Matrix of Hepatic Stellate Cells and Ameliorate Hepatic Fibrosis in Mice
title_full_unstemmed Gypenosides Synergistically Reduce the Extracellular Matrix of Hepatic Stellate Cells and Ameliorate Hepatic Fibrosis in Mice
title_short Gypenosides Synergistically Reduce the Extracellular Matrix of Hepatic Stellate Cells and Ameliorate Hepatic Fibrosis in Mice
title_sort gypenosides synergistically reduce the extracellular matrix of hepatic stellate cells and ameliorate hepatic fibrosis in mice
topic gypenoside
liver fibrosis
PP2Cα
extracellular matrix
synergistic effect
url https://www.mdpi.com/1420-3049/28/14/5448
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