Traditional Chinese Medicine Ganshuang Granules Attenuate CCl<sub>4</sub>‐Induced Hepatic Fibrosis by Modulating Gut Microbiota

Zhao, Jie; Miao, Jing; Wei, Xinyuan; Guo, Liying; Lei, Jinyan; Wang, Jing; Zhu, Bo; Wang, Li; Jia, Jianwei

doi:10.1002/cbdv.202100520

Cited by 13 publications

(9 citation statements)

References 40 publications

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“…For example, Xiaoyaosan decoction, containing eight Chinese herbs, was reported to prevent the progression of liver fibrosis induced by CCl 4 in rats, which was mediated through transforming growth factor beta1 (TGFβ1)/Smad signaling cascades (Zhou et al, 2021). Ganshuang granules, a prepared TCM decoction, can regulate gut microbiota composition and diversity to maintain intestinal integrity and exert antioxidant and anti-inflammatory effects, therefore repressing liver fibrosis (Zhao et al, 2021). Yiguanjian decoction, a representative TCM comprising six medicinal herbs, inhibits liver fibrosis by maintaining the resting state of hepatic stellate cells and hepatocyte viability (Li et al, 2019), repressing liver angiogenesis (Zhou et al, 2015), and modulating inflammatory cytokine release from macrophages .…”

Section: Introductionmentioning

confidence: 99%

Hepatoprotective Efficacy and Interventional Mechanism of Qijia Rougan Decoction in Liver Fibrosis

Chen

Wang

et al. 2022

Front. Pharmacol.

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Liver fibrosis is a leading contributor to chronic liver diseases such as cirrhosis and liver cancer, which pose a serious health threat worldwide, and there are no effective drugs to treat it. Qijia Rougan decoction was modified from Sanjiasan, a traditional Chinese medicine (TCM) described in the “Wenyilun” manuscript. Qijia Rougan decoction possesses hepatoprotective and antifibrotic effects for clinical applications. However, its underlying mechanisms remain largely unknown. In this study, fibrotic rats induced by carbon tetrachloride (CCl4) were treated with two doses of Qijia Rougan decoction. Histopathological and serum biochemical analyses were carried out to assess liver structure and function, respectively. High-performance liquid chromatography (HPLC) coupled with mass spectrometry (MS) was performed to identify bioactive compositions in Qijia Rougan decoction. Transcriptome analysis using mRNA-sequencing (mRNA-Seq) was used to explore the underlying mechanisms and verified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Qijia Rougan decoction significantly attenuated CCl4-induced hepatic fibrotic injury, supported by promoted liver function and improved liver fibrosis. Eight main representative components originating from raw materials in the Qijia Rougan decoction were found to possess an antifibrotic role. Mechanistically, Qijia Rougan decoction regulated biological processes such as oxidation–reduction, fatty acid metabolism, cell adhesion, and transforming growth factor beta (TGFβ) signaling. We determined that Qijia Rougan decoction reversed the expression of inflammatory cytokines and inhibited the activation of fibrosis-related TGFβ signaling. It also reversed the deterioration of liver structure and function in rats induced by CCl4. Overall, Qijia Rougan decoction significantly mediated metabolism-associated processes, inhibited inflammatory reactions, and repressed fibrosis-related TGFβ signaling, which prevented liver fibrosis deterioration. Our study deepens our understanding of TCM in the diagnosis and treatment of liver fibrosis.

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Section: Introductionmentioning

confidence: 99%

Hepatoprotective Efficacy and Interventional Mechanism of Qijia Rougan Decoction in Liver Fibrosis

Chen

Wang

et al. 2022

Front. Pharmacol.

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“…A TCM composed of Gardeniae Fructus and Semen Sojae Praeparatum, named Zhizichi Decoction, was found to reduce liver injury by regulating the gut microbiota population, promoting butyric acid production and activating the antioxidant reaction ( 48 ). In addition, Ganshuang Granules [composed of Chinese herbs such as Radix Codonopsis, Bupleurum Falcatum and Salviae Miltiorrhiza] can rebalance the gut microbiota and reduce intestinal permeability, thereby reducing oxidative stress and inflammation and ultimately ameliorating CCl 4 -induced hepatotoxicity and ALI ( 49 ). At present, the potential roles of these agents based on gut microbiota in alleviating hepatotoxicity and ALI have been constantly explored, which not only provides a promising target for the prevention and treatment of the disease but also deepens the awareness of the important research value of TCMs and NPs in disease treatment.…”

Section: Targeting Gut Microbiota For Acute Liver Injurymentioning

confidence: 99%

Targeted modulation of gut microbiota by traditional Chinese medicine and natural products for liver disease therapy

Zhu

Zheng

et al. 2023

Front. Immunol.

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The gut microbiota not only constitutes intestinal microenvironment homeostasis and human health but also exerts indispensable roles in the occurrence and progression of multiple liver diseases, including alcohol-related liver disease, nonalcoholic fatty liver disease, autoimmune liver disease and liver cancer. Given the therapeutic status of these diseases, their prevention and early therapy are crucial, and the detailed mechanism of gut microbiota in liver disease urgently needs to be explored. Meanwhile, multiple studies have shown that various traditional Chinese medicines, such as Si Miao Formula, Jiangzhi Granules, Liushen Capsules, Chaihu-Shugan Power, Cassiae Semen and Gynostemma, as well as some natural products, including Costunolide, Coprinus comatus polysaccharide, Antarctic krill oil, Oridonin and Berberine, can repair liver injury, improve fatty liver, regulate liver immunity, and even inhibit liver cancer through multiple targets, links, and pathways. Intriguingly, the aforementioned effects demonstrated by these traditional Chinese medicines and natural products have been shown to be closely related to the gut microbiota, directly driving the strategy of traditional Chinese medicines and natural products to regulate the gut microbiota as one of the breakthroughs in the treatment of liver diseases. Based on this, this review comprehensively summarizes and discusses the characteristics, functions and potential mechanisms of these medicines targeting gut microbiota during liver disease treatment. Research on the potential effects on gut microbiota and the regulatory mechanisms of traditional Chinese medicine and natural products provides novel insights and significant references for developing liver disease treatment strategies. In parallel, such explorations will enhance the comprehension of traditional Chinese medicine and natural products modulating gut microbiota during disease treatment, thus facilitating their clinical investigation and application.

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“…The formula contains 13 herbs, such as Bupleuri Radix , Angelicae Sinensis Radix , Poria, and Salviae Miltiorrhizae Radix et Rhizoma , which have good therapeutic effects on clinical acute and chronic hepatitis and liver cirrhosis ( Shi et al, 2017 ; Zeng et al, 2020 ; Lu et al, 2021 ). Modern pharmacological studies indicated that GSG can regulate the intestinal microbiota and moderate CCl4-induced liver fibrosis ( Zhao et al, 2021 ). In addition, GSG can slow the progression of liver fibrosis by impeding mTOR-autophagy to inhibit the activation of hepatic stellate cells (HSCs) ( Shi et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Exploring the molecular mechanism of Gan Shuang granules for the treatment of non-alcoholic steatohepatitis using network pharmacology, molecular docking, and experimental verification

et al. 2023

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Background: With the gradual increase in prevalence in recent years, non-alcoholic steatohepatitis (NASH) has become one of the significant health problems that urgently needs to be addressed worldwide. GanShuang Granules (GSG) is derived from the classical Chinese formula Xiaoyao San and mainly used in the clinical treatment of chronic liver diseases.Objective: In this study, we aim to gain a deeper insight into the inhibiting effects of GSG on non-alcoholic fatty liver disease (NAFLD) rats and preliminarily elucidate the underlying intervention mechanisms.Methods: First, High performance liquid chromatography (UHPLC-Q/Orbitrap-MS/MS) was used for the active compounds prediction in GSG. Then the data was mapped to mzCloud database. The targets corresponding to GSG compounds were collected from public databases, along with disease genes for NAFLD. The core targets and molecular mechanisms of GSG for NAFLD treatment were predicted by protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. Molecular docking of the core target-component interactions was simulated using AutoDock Vina software. The effect of GSG on NASH rats was evaluated by pathological staining and analysis of various index results. Finally, the candidate targets were further validated by ELISA and western blot (WB) analyses.Results: Combining UHPLC-Q/Orbitrap-MS/MS data analysis and public database data, a total of 346 cross-targets were obtained, corresponding to 81 compounds. The subnetwork with an MCODE score of 53.623 is a potential core target group for this study. GO and KEGG enrichment analyses showed that the targets of GSG in NAFLD were mostly related to oxidative stress, the NF-κB signaling pathway, and the apoptosis signaling pathway. By integrating the results of network pharmacology analysis, the core objectives of this study mainly include AKT1, CASP9, TNF, and CASP8. The core ingredients are related to resveratrol and fisetin. The molecular docking results indicated key binding activity between AKT1-fisetin, AKT1-Resveratrol, and CASP8-fisetin. Moreover, GSG could improve the inflammatory status and restore the abnormal lipid accumulation of NAFLD/NASH liver, and these levels are further verified by pathological staining and detection of related indicators. Mechanistically, GSG could regulate protein expression levels in the liver for P65, p-P65, IKB, p-IKB, IKK, caspase-3, -8, -9, and cytochrome C, etc. It reflects the inhibitory effect of GSG on the NF-κB/IκB signaling pathway.Conclusion: Our results suggested that GSG demonstrated therapeutic effects on NAFLD/NASH rats, and these may be mainly reflected in the inhibitory effects on the NF-κB/IκB signaling pathway and its downstream inflammation and apoptosis signals.

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Traditional Chinese Medicine Ganshuang Granules Attenuate CCl₄‐Induced Hepatic Fibrosis by Modulating Gut Microbiota

Cited by 13 publications

References 40 publications

Hepatoprotective Efficacy and Interventional Mechanism of Qijia Rougan Decoction in Liver Fibrosis

Hepatoprotective Efficacy and Interventional Mechanism of Qijia Rougan Decoction in Liver Fibrosis

Targeted modulation of gut microbiota by traditional Chinese medicine and natural products for liver disease therapy

Exploring the molecular mechanism of Gan Shuang granules for the treatment of non-alcoholic steatohepatitis using network pharmacology, molecular docking, and experimental verification

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Traditional Chinese Medicine Ganshuang Granules Attenuate CCl4‐Induced Hepatic Fibrosis by Modulating Gut Microbiota

Cited by 13 publications

References 40 publications

Hepatoprotective Efficacy and Interventional Mechanism of Qijia Rougan Decoction in Liver Fibrosis

Hepatoprotective Efficacy and Interventional Mechanism of Qijia Rougan Decoction in Liver Fibrosis

Targeted modulation of gut microbiota by traditional Chinese medicine and natural products for liver disease therapy

Exploring the molecular mechanism of Gan Shuang granules for the treatment of non-alcoholic steatohepatitis using network pharmacology, molecular docking, and experimental verification

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Traditional Chinese Medicine Ganshuang Granules Attenuate CCl₄‐Induced Hepatic Fibrosis by Modulating Gut Microbiota