Mechanisms exploration of Angelicae Sinensis Radix and Ligusticum Chuanxiong Rhizoma herb-pair for liver fibrosis prevention based on network pharmacology and experimental pharmacologylogy

2021 ◽  
Vol 19 (4) ◽  
pp. 241-254
Author(s):  
Jian-Zhi WU ◽  
Ya-Jing LI ◽  
Guang-Rui HUANG ◽  
Bing XU ◽  
Fei ZHOU ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Network Pharmacology ◽  
Ligusticum Chuanxiong ◽  
Angelicae Sinensis

scholarly journals Insights into the molecular mechanisms of Huangqi decoction on liver fibrosis via computational systems pharmacology approaches

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Biting Wang ◽  
Zengrui Wu ◽  
Weihua Li ◽  
Guixia Liu ◽  
Yun Tang
Keyword(s):  
Molecular Docking ◽  
Liver Fibrosis ◽  
Molecular Mechanisms ◽  
Docking Simulation ◽  
Chinese Herbs ◽  
Network Pharmacology ◽  
Bipartite Network ◽  
Metabolomics Data ◽  
Metabolic Products ◽  
Compound Target

Abstract Background The traditional Chinese medicine Huangqi decoction (HQD) consists of Radix Astragali and Radix Glycyrrhizae in a ratio of 6: 1, which has been used for the treatment of liver fibrosis. In this study, we tried to elucidate its action of mechanism (MoA) via a combination of metabolomics data, network pharmacology and molecular docking methods. Methods Firstly, we collected prototype components and metabolic products after administration of HQD from a publication. With known and predicted targets, compound-target interactions were obtained. Then, the global compound-liver fibrosis target bipartite network and the HQD-liver fibrosis protein–protein interaction network were constructed, separately. KEGG pathway analysis was applied to further understand the mechanisms related to the target proteins of HQD. Additionally, molecular docking simulation was performed to determine the binding efficiency of compounds with targets. Finally, considering the concentrations of prototype compounds and metabolites of HQD, the critical compound-liver fibrosis target bipartite network was constructed. Results 68 compounds including 17 prototype components and 51 metabolic products were collected. 540 compound-target interactions were obtained between the 68 compounds and 95 targets. Combining network analysis, molecular docking and concentration of compounds, our final results demonstrated that eight compounds (three prototype compounds and five metabolites) and eight targets (CDK1, MMP9, PPARD, PPARG, PTGS2, SERPINE1, TP53, and HIF1A) might contribute to the effects of HQD on liver fibrosis. These interactions would maintain the balance of ECM, reduce liver damage, inhibit hepatocyte apoptosis, and alleviate liver inflammation through five signaling pathways including p53, PPAR, HIF-1, IL-17, and TNF signaling pathway. Conclusions This study provides a new way to understand the MoA of HQD on liver fibrosis by considering the concentrations of components and metabolites, which might be a model for investigation of MoA of other Chinese herbs.

scholarly journals Network Pharmacological Analysis and Experimental Validation of the Mechanisms of Action of Si-Ni-San Against Liver Fibrosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Siliang Wang ◽  
Cheng Tang ◽  
Heng Zhao ◽  
Peiliang Shen ◽  
Chao Lin ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Mechanisms Of Action ◽  
Network Pharmacology ◽  
Related Factor ◽  
Alcoholic Fatty Liver ◽  
Ppar Γ ◽  
Liver Tissues

Background: Si-Ni-San (SNS), a commonly used traditional Chinese medicine (TCM) formula, has potency against liver diseases, such as hepatitis and non-alcoholic fatty liver disease (NAFLD). However, the therapeutic efficacy and pharmacological mechanisms of action of SNS against liver fibrosis remain largely unclear.Methods: A carbon tetrachloride (CCl4)-induced liver fibrosis mouse model was adopted for the first time to investigate the beneficial effects of SNS on liver fibrosis. The potential mechanisms of action of SNS were explored using the network pharmacology-based strategy and validated with the aid of diverse assays.Results: SNS treatment reduced collagen and ECM deposition, downregulated fibrosis-related factor (hyaluronic acid and laminin) contents in serum, maintained the morphological structure of liver tissue, and improved liver function in the liver fibrosis model. Based on network pharmacology results, apoptosis, inflammation and angiogenesis, together with the associated pathways (including VEGF, TNF, caspase, PPAR-γ and NF-κB), were identified as the mechanisms underlying the effects of SNS on liver fibrosis. Further in vivo experiments validated the significant mitigatory effects of SNS on inflammatory infiltration and pro-inflammatory cytokine contents (IFNγ, IL-1β and TGF-β1) in liver tissues of mice with liver fibrosis. SNS suppressed pathologic neovascularization as well as levels of VEGFR1, VEGF and VEGFR2 in liver tissues. SNS treatment additionally inhibited hepatic parenchyma cell apoptosis in liver tissues of mice with liver fibrosis and regulated apoptin expression while protecting L02 cells against apoptosis induced by TNF-α and Act D in vitro. Activation of hepatic stellate cells was suppressed and the balance between MMP13 and TIMP1 maintained in vitro by SNS. These activities may be associated with SNS-induced NF-κB suppression and PPAR-γ activation.Conclusion: SNS effectively impedes liver fibrosis progression through alleviating inflammation, ECM accumulation, aberrant angiogenesis and apoptosis of hepatic parenchymal cells along with inhibiting activation of hepatic stellate cells through effects on multiple targets and may thus serve as a novel therapeutic regimen for this condition.

scholarly journals Elucidating the Mechanisms of Hugan Buzure Granule in the Treatment of Liver Fibrosis via Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yi Zhu ◽  
Ming Qiao ◽  
Jianhua Yang ◽  
Junping Hu
Keyword(s):  
Liver Fibrosis ◽  
Rna Polymerase Ii ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Docking Simulation ◽  
Interaction Network ◽  
Network Pharmacology ◽  
Transcription Activator ◽  
Active Ingredients ◽  
Oxidoreductase Activity

Objective. To holistically explore the latent active ingredients, targets, and related mechanisms of Hugan buzure granule (HBG) in the treatment of liver fibrosis (LF) via network pharmacology. Methods. First, we collected the ingredients of HBG by referring the TCMSP server and literature and filtered the active ingredients though the criteria of oral bioavailability ≥30% and drug-likeness index ≥0.18. Second, herb-associated targets were predicted and screened based on the BATMAN-TCM and SwissTargetPrediction platforms. Candidate targets related to LF were collected from the GeneCards and OMIM databases. Furthermore, the overlapping target genes were used to construct the protein-protein interaction network and “drug-compound-target-disease” network. Third, GO and KEGG pathway analyses were carried out to illustrate the latent mechanisms of HBG in the treatment of LF. Finally, the combining activities of hub targets with active ingredients were further verified based on software AutoDock Vina. Results. A total of 25 active ingredients and 115 overlapping target genes of HBG and LF were collected. Besides, GO enrichment analysis exhibited that the overlapping target genes were involved in DNA-binding transcription activator activity, RNA polymerase II-specific, and oxidoreductase activity. Simultaneously, the key molecular mechanisms of HBG against LF were mainly involved in PI3K-AKT, MAPK, HIF-1, and NF-κB signaling pathways. Also, molecular docking simulation demonstrated that the key targets of HBG for antiliver fibrosis were IL6, CASP3, EGFR, VEGF, and MAPK. Conclusion. This work validated and predicted the underlying mechanisms of multicomponent and multitarget about HBG in treating LF and provided a scientific foundation for further research.

A network pharmacology approach to investigating the mechanism of Tanshinone IIA for the treatment of liver fibrosis

2020 ◽  
Vol 253 ◽  
pp. 112689 ◽  
Author(s):  
Miao-Juan Shi ◽  
Xiu-Li Yan ◽  
Ben-Sheng Dong ◽  
Wen-Na Yang ◽  
Shi-Bing Su ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Tanshinone Iia ◽  
Network Pharmacology

scholarly journals Network Pharmacology Analysis and Molecular Characterization of the Herbal Medicine Formulation Qi-Fu-Yin for the Inhibition of the Neuroinflammatory Biomarker iNOS in Microglial BV-2 Cells: Implication for the Treatment of Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Fung Yin Ngo ◽  
Weiwei Wang ◽  
Qilei Chen ◽  
Jia Zhao ◽  
Hubiao Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Selective Inhibition ◽  
Network Pharmacology ◽  
Herbal Formula ◽  
Active Compounds ◽  
Protein Targets ◽  
Blotting Technique ◽  
Cox 2 ◽  
Angelicae Sinensis

Aberrant microglial activation drives neuroinflammation and neurodegeneration in Alzheimer’s disease (AD). The present study is aimed at investigating whether the herbal formula Qi-Fu-Yin (QFY) could inhibit the inflammatory activation of cultured BV-2 microglia. A network pharmacology approach was employed to predict the active compounds of QFY, protein targets, and affected pathways. The representative pathways and molecular functions of the targets were analyzed by Gene Ontology (GO) and pathway enrichment. A total of 145 active compounds were selected from seven herbal ingredients of QFY. Targets (e.g., MAPT, APP, ACHE, iNOS, and COX-2) were predicted for the selected active compounds based on the relevance to AD and inflammation. As a validation, fractions were sequentially prepared by aqueous extraction, ethanolic precipitation, and HPLC separation, and assayed for downregulating two key proinflammatory biomarkers iNOS and COX-2 in lipopolysaccharide- (LPS-) challenged BV-2 cells by the Western blotting technique. Moreover, the compounds of QFY in 90% ethanol downregulated iNOS in BV-2 cells but showed no activity against COX-2 induction. Among the herbal ingredients of QFY, Angelicae Sinensis Radix and Ginseng Radix et Rhizoma contributed to the selective inhibition of iNOS induction. Furthermore, chemical analysis identified ginsenosides, especially Rg3, as antineuroinflammatory compounds. The herbal formula QFY may ameliorate neuroinflammation via downregulating iNOS in microglia.

scholarly journals Development of A Novel Anti-Liver Fibrosis Formula with luteolin, licochalcone A, aloe-emodin and acacetin by network pharmacology and transcriptomics analysis

2020 ◽  
Author(s):  
Yuan Zhou ◽  
Rong Wu ◽  
Fei-Fei Cai ◽  
Wen-Jun Zhou ◽  
Yi-Yu Lu ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Topological Analysis ◽  
Deficiency Syndrome ◽  
Network Pharmacology ◽  
Individual Compound ◽  
Licochalcone A ◽  
Spleen Deficiency ◽  
Ppar Signaling ◽  
Aloe Emodin ◽  
Spleen Deficiency Syndrome

Abstract Background: Liver fibrosis leads to loss of liver function. Xiaoyaosan decoction (XYS) as a classical Traditional Chinese Medicine (TCM) formula is used to treatment liver fibrosis in clinical and alleviated CCl4-induced liver fibrosis in our previous study.Xiaoyaosan decoction was composed of many ingredients, and the active ingredients is not clear. The Aim of this study is to explore the clarified compounds or compound combinations to treat liver fibrosis.Methods: Network pharmacology combined with transcriptomics analysis were used to analyze the Xiaoyaosan decoction (XYS) and liver depression and spleen deficiency syndrome liver fibrosis. This consisted constructed XYS-Syndrome-liver fibrosis network, the predict formula named LLAAF was develop from the network by topological analysis according to network stability. The anti-fibrosis effect was evaluated by in vitro and in vivo study.Results: According to the network XYS-Syndrome-liver fibrosis network, luteolin, licochalcone A, aloe-emodin, and acacetin formula (LLAAF) was predicted from 8 key compounds and 255 combinations in XYS, and LLAAF had a synergistic effect on the proliferation inhibition of hepatic stellate cells (HSCs) compared to each individual compound alone. The treatment of XYS and LLAAF showed a similar anti-liver fibrotic effect that reduced histopathological changes of liver fibrosis, Hyp content and levels of α-SMA and collagen I in CCl4-induced liver fibrosis in rat. Transcriptomics analysis revealed LLAAF regulated PI3K-Akt, AMPK, FoxO, Jak-STAT3, P53, cell cycle, focal adhesion, and PPAR signaling. Furthermore, LLAAF was confirmed to regulate Jak-STAT and PI3K-Akt-FoxO signaling in vitro and in vivo.Conclusions: This study developed a novel anti-liver formula, LLAAF from XYS demonstrated the anti-liver fibrotic activity may be involved in the regulation of Jak-STAT and PI3K-Akt-FoxO signaling.

scholarly journals The Chinese Herbal Decoction Danggui Buxue Tang Inhibits Angiogenesis in a Rat Model of Liver Fibrosis

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Jing Lv ◽  
Zhimin Zhao ◽  
Yuan Chen ◽  
Qinglan Wang ◽  
Yanyan Tao ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Rat Model ◽  
Sod Activity ◽  
Danggui Buxue Tang ◽  
Radix Angelicae Sinensis ◽  
Chinese Herbal ◽  
Gene And Protein Expression ◽  
Herbal Decoction ◽  
Angiogenic Effect ◽  
Angelicae Sinensis

In this study, we investigated the anti-angiogenic effect of the Chinese herbal decoction Danggui Buxue Tang (DBT;Radix AstragaliandRadix Angelicae sinensisin 5 : 1 ratio) in a rat model of liver fibrosis, in order to elucidate its mechanisms of action against liver fibrosis. Liver fibrosis was induced with CCl4and high-fat food for 6 weeks, and the rats were treated with oral doses of DBT (6 g raw herbs/kg/d) and N-Acetyl-L-cysteine (NAC; 0.1 g/kg/d). The results showed that both DBT and NAC attenuated liver fibrosis and neo-angiogenesis. Furthermore, DBT and NAC improved SOD activity but decreased MDA content and 8-OH-dG in fibrotic livers, with DBT being more effective than NAC. DBT decreased the expression of VEGF, Ang1 and TGF-β1 and their signaling mediators, whereas NAC had no effect on VEGF and VEGFR2 expression. Both DBT and NAC reduced HIF-1αgene and protein expression in fibrotic livers, with DBT being more effective. These data clearly demonstrate that the anti-fibrotic properties of DBT are related to its ability to inhibit angiogenesis and its anti-angiogenic mechanisms are associated with improving oxidative stress, regulating the expression and signaling of angiogenic factors, and especially modulating HIF-1αin fibrotic livers.

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