Anti-Liver Fibrosis Activity and the Potential Mode of Action of Ruangan Granules: Integrated Network Pharmacology and Metabolomics

Ruangan granules (RGGs) have been used to treat liver fibrosis with good clinical efficacy for many years. However, the potential mechanism of action of RGGs against liver fibrosis is still unclear. In this study, we evaluated the quality and safety of this preparation and aimed to explore the anti-...

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Main Authors: Xiaofei Shang, Huixin Yuan, Lixia Dai, Yang Liu, Jian He, Huan Chen, Hongyan Li, Xiuhui Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-01-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2021.754807/full
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author Xiaofei Shang
Xiaofei Shang
Huixin Yuan
Lixia Dai
Yang Liu
Jian He
Huan Chen
Hongyan Li
Xiuhui Li
author_facet Xiaofei Shang
Xiaofei Shang
Huixin Yuan
Lixia Dai
Yang Liu
Jian He
Huan Chen
Hongyan Li
Xiuhui Li
author_sort Xiaofei Shang
collection DOAJ
description Ruangan granules (RGGs) have been used to treat liver fibrosis with good clinical efficacy for many years. However, the potential mechanism of action of RGGs against liver fibrosis is still unclear. In this study, we evaluated the quality and safety of this preparation and aimed to explore the anti-liver fibrosis activity and potential mode of action of RGGs using network pharmacology and metabolomics. The results showed that RGGs contained abundant ferulic acid, salvianolic acid B and paeoniflorin, and at the given contents and doses, RGGs were safe and presented anti-liver fibrosis activity. They presented anti-liver fibrosis activity by improving liver function (ALT and AST, p < 0.01) and pathology and decreasing fibrosis markers in the serum of rats caused by CCl4, including HA, LN, PC III, HYP, CoII-V, and α-SMA, and the oxidant stress and inflammatory response were also alleviated in a dose-dependent manner, especially for high-dose RGGs (p < 0.01). Further studies showed that RGGs inhibited the activation of the PI3K-Akt signaling pathway in rats induced by CCl4, regulated pyrimidine metabolism, improved oxidative stress and the inflammatory response by regulating mitochondrial morphology, and alleviated liver fibrosis. Luteolin, quercetin, morin and kaempferol were active compounds and presented the cytotoxicity toward to LX-02 cells. This study provides an overall view of the mechanism underlying the action of RGGs protecting against liver fibrosis.
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spelling doaj.art-38d0e770a8d94b809fa3f9893a4cd3272022-12-22T04:13:13ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-01-011210.3389/fphar.2021.754807754807Anti-Liver Fibrosis Activity and the Potential Mode of Action of Ruangan Granules: Integrated Network Pharmacology and MetabolomicsXiaofei Shang0Xiaofei Shang1Huixin Yuan2Lixia Dai3Yang Liu4Jian He5Huan Chen6Hongyan Li7Xiuhui Li8Beijing YouAn Hospital, Capital Medical University, Beijing, ChinaLanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaBeijing YouAn Hospital, Capital Medical University, Beijing, ChinaLanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaBeijing YouAn Hospital, Capital Medical University, Beijing, ChinaLanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaBeijing YouAn Hospital, Capital Medical University, Beijing, ChinaBeijing YouAn Hospital, Capital Medical University, Beijing, ChinaBeijing YouAn Hospital, Capital Medical University, Beijing, ChinaRuangan granules (RGGs) have been used to treat liver fibrosis with good clinical efficacy for many years. However, the potential mechanism of action of RGGs against liver fibrosis is still unclear. In this study, we evaluated the quality and safety of this preparation and aimed to explore the anti-liver fibrosis activity and potential mode of action of RGGs using network pharmacology and metabolomics. The results showed that RGGs contained abundant ferulic acid, salvianolic acid B and paeoniflorin, and at the given contents and doses, RGGs were safe and presented anti-liver fibrosis activity. They presented anti-liver fibrosis activity by improving liver function (ALT and AST, p < 0.01) and pathology and decreasing fibrosis markers in the serum of rats caused by CCl4, including HA, LN, PC III, HYP, CoII-V, and α-SMA, and the oxidant stress and inflammatory response were also alleviated in a dose-dependent manner, especially for high-dose RGGs (p < 0.01). Further studies showed that RGGs inhibited the activation of the PI3K-Akt signaling pathway in rats induced by CCl4, regulated pyrimidine metabolism, improved oxidative stress and the inflammatory response by regulating mitochondrial morphology, and alleviated liver fibrosis. Luteolin, quercetin, morin and kaempferol were active compounds and presented the cytotoxicity toward to LX-02 cells. This study provides an overall view of the mechanism underlying the action of RGGs protecting against liver fibrosis.https://www.frontiersin.org/articles/10.3389/fphar.2021.754807/fullruangan granulesliver fibrosisnetwork pharmacologymetabolomicsmode of action
spellingShingle Xiaofei Shang
Xiaofei Shang
Huixin Yuan
Lixia Dai
Yang Liu
Jian He
Huan Chen
Hongyan Li
Xiuhui Li
Anti-Liver Fibrosis Activity and the Potential Mode of Action of Ruangan Granules: Integrated Network Pharmacology and Metabolomics
Frontiers in Pharmacology
ruangan granules
liver fibrosis
network pharmacology
metabolomics
mode of action
title Anti-Liver Fibrosis Activity and the Potential Mode of Action of Ruangan Granules: Integrated Network Pharmacology and Metabolomics
title_full Anti-Liver Fibrosis Activity and the Potential Mode of Action of Ruangan Granules: Integrated Network Pharmacology and Metabolomics
title_fullStr Anti-Liver Fibrosis Activity and the Potential Mode of Action of Ruangan Granules: Integrated Network Pharmacology and Metabolomics
title_full_unstemmed Anti-Liver Fibrosis Activity and the Potential Mode of Action of Ruangan Granules: Integrated Network Pharmacology and Metabolomics
title_short Anti-Liver Fibrosis Activity and the Potential Mode of Action of Ruangan Granules: Integrated Network Pharmacology and Metabolomics
title_sort anti liver fibrosis activity and the potential mode of action of ruangan granules integrated network pharmacology and metabolomics
topic ruangan granules
liver fibrosis
network pharmacology
metabolomics
mode of action
url https://www.frontiersin.org/articles/10.3389/fphar.2021.754807/full
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