A Network Pharmacology-Based Study on Active Ingredients of Corydalis Rhizoma on Coronary Heart Disease

Abstract BackgroundCorydalis Rhizoma(CR) showed a high efficacy for coronary heart disease (CHD). However, the interaction between the active ingredients of CR and the targets of CHD has not been unequivocally explained in previous researches. To study the active components and potential targets of Corydalis Rhizoma and to determine the mechanism underlying the exact effect of Corydalis Rhizoma on coronary heart disease, a method of network pharmacology was used.Materials and MethodsThe active components of CR and targets corresponding to each component were scanned out from Traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and target genes of CHD were searched on GeneCards database and Online Mendelian Inheritance in Man(OMIM) database. The active components and common targets of CR and CHD were used to build the “CR-CHD” network through Cytoscape (version 3.2.1) software as well as protein-protein interaction(PPI) network on String database. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis was executed by clusterProfiler(version 3.8) and DOSE(version 3.6) package on R platform.Results49 active ingredients and 394 relevant targets of CR and the 7173 CHD-related genes were retrieved. 40 common genes were selected for subsequent analysis. Crucial biological processes and pathways were obtained and analyzed, including DNA-binding transcription activator activity, RNA polymerase II-specific, RNA polymerase II transcription factor binding, kinase regulator activity, ubiquitin-like protein ligase binding, fluid shear stress and atherosclerosis, TNF signaling pathway, apoptosis, MAPK signaling pathway and PI3K-Akt signaling pathway.ConclusionsOverall, CR could alleviate CHD through the mechanisms predicted by network pharmacology, laying the foundation for future development of new drugs from traditional Chinese medicine on CHD.

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A Network Pharmacology-Based Study on Active Ingredients of Corydalis Rhizoma on Coronary Heart Disease

10.21203/rs.3.rs-41449/v1 ◽

2020 ◽

Author(s):

Ying Li ◽

Guhang Wei ◽

Zhenkun Zhuang ◽

Mingtai Chen ◽

Haidan Lin ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Rna Polymerase ◽

Rna Polymerase Ii ◽

Signaling Pathway ◽

Network Pharmacology ◽

Active Ingredients ◽

Active Components

Abstract Background. Corydalis Rhizoma(CR) showed a high efficacy for coronary heart disease (CHD). However, the interaction between the active ingredients of CR and the targets of CHD has not been unequivocally explained in previous researches. To study the active components and potential targets of Corydalis Rhizoma and to determine the mechanism underlying the exact effect of Corydalis Rhizoma on coronary heart disease, a method of network pharmacology was used. Materials and Methods. The active components of CR and targets corresponding to each component were scanned out from Traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and target genes of CHD were searched on GeneCards database and Online Mendelian Inheritance in Man(OMIM) database. The active components and common targets of CR and CHD were used to build the “CR-CHD” network through Cytoscape (version 3.2.1) software as well as protein-protein interaction(PPI) network on String database. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis was executed by clusterProfiler(version 3.8) and DOSE(version 3.6) package on R platform. Results. 49 active ingredients and 394 relevant targets of CR and the 7173 CHD-related genes were retrieved. 40 common genes were selected for subsequent analysis. Crucial biological processes and pathways were obtained and analyzed, including DNA-binding transcription activator activity, RNA polymerase II-specific, RNA polymerase II transcription factor binding, kinase regulator activity, ubiquitin-like protein ligase binding, fluid shear stress and atherosclerosis, TNF signaling pathway, apoptosis, MAPK signaling pathway and PI3K-Akt signaling pathway. Conclusions. Overall, CR could alleviate CHD through the mechanisms predicted by network pharmacology, laying the foundation for future development of new drugs from traditional Chinese medicine on CHD.

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Investigating the pharmacological mechanisms of SheXiang XinTongNing against coronary heart disease based on network pharmacology

10.21203/rs.3.rs-21814/v1 ◽

2020 ◽

Author(s):

Li-ying Jia ◽

Jia Li ◽

Gui-yun Cao ◽

Zhao-qing Meng ◽

Lu Gan ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Signaling Pathway ◽

Protein Interaction ◽

Protein Interaction Network ◽

Interaction Network ◽

Enrichment Analysis ◽

Network Pharmacology

Abstract Background SheXiang XinTongNing, a commercially available Chinese patent medicine, has been widely used in the treatment of coronary heart disease. However, the mechanisms of SheXiang XinTongNing are still unclear. The aim of this study was to investigate the pharmacological mechanisms of SheXiang XinTongNing against coronary heart disease via network analysis. Method The traditional Chinese medicine system pharmacology analysis platform was used to screen the potential active constituents of the six traditional Chinese medicines in SheXiang XinTongNing, and the potential targets were obtained from PharmMapper. The genome annotation database platform was used to screen the candidate targets related to coronary heart disease. Then the drug-components-targets network and protein interaction network were built by Cytoscape 3.6.0 software. Further, GO bio-functional enrichment analysis and KEGG pathway enrichment analysis were performed through annotation, visualization and integrated discovery database. Results Results showed that the drugs-components-targets network contains 104 targets and 62 key components. The protein interaction network consisted of 107 nodes; key targets included Bcl2l1, IGF1, SRC, CASP3, et al. Functionally, the candidate targets were significantly associated with multiple pathways such as PI3K-Akt signaling pathway, MAPK signaling pathway, Ras signaling pathway, FoxO signaling pathway, Endocrine resistance. Given the above, the pharmacological activities of SheXiang XinTongNing may be predominantly related to several factors such as cell apoptosis, inflammation and angiogenesis. Conclusion XTN can effectively attenuate the symptoms of coronary heart disease through diverse pathways. The research proves that network pharmacology can successfully reveal the mechanisms of traditional Chinese medicine in a holistic view. Our systematic analysis lays a foundation for further studying.

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A Multi-Scale Bioinformatics Study on Novel Mechanism of Xintong Granule for Treating Coronary Heart Disease by Network Pharmacology and Molecular Docking Verification

10.21203/rs.3.rs-116130/v1 ◽

2020 ◽

Author(s):

Zhihong Huang ◽

Siyu Guo ◽

Changgeng Fu ◽

Wei Zhou ◽

Jingyuan Zhang ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Molecular Docking ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Signaling Pathway ◽

Chinese Herbs ◽

Network Pharmacology ◽

Pharmacological Mechanism ◽

Vascular Regulation

Abstract Background: Xintong Granule (XTG) is a Chinese patent medicine composed of 13 Chinese herbs, which is widely used in the treatment of coronary heart disease (CHD). However, there are few studies on it, and its potential pharmacological mechanism needs to be further elucidated.Methods: In this study, network pharmacology was employed to construct the drug-compounds-targets-pathways molecular regulatory network of the treatment of CHD to explore the effective compounds of XTG and its underlying pharmacological mechanism. First, we established the related ingredients and potential targets of these ingredients databases by Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and A Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM). Next, the CHD targets were obtained in DigSee, OMIM, DisGeNET, TTD, GeneCards and GenCLiP3 database. Then, protein-protein interaction (PPI) analysis, GO and KEGG pathway enrichment analysis were carried out and the core targets were filtered by topology. Moreover, molecular docking was performed to assess the binding potential of hub targets and key compounds.Results: The result reflected that 178 components of XTG and 669 putative therapeutic targets were screened out. After a systematic and comprehensive analysis, we identified 9 hub targets (TNF, MAPK1, STAT3, IL6, AKT1, INS, EGFR, EGF, TP53) primarily participated in the comprehensive therapeutic effect related to blood circulation, vascular regulation, cell membrane region, compound binding, receptor activity, signal transduction, AGE-RAGE signaling pathway in diabetic complications, JAK-STAT signaling pathway, PI3K-AKT signaling pathway and MAPK signaling pathway.Conclusion: The results of this study tentatively clarified the potential targets and signaling pathways of XTG against CHD, which may benefit to the development of clinical experimental research and application.

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Discussion on the Mechanism of Action of High-frequency Drugs for Treating Heart Failure Based on Network Pharmacology

Journal of Clinical and Nursing Research ◽

10.26689/jcnr.v5i3.1996 ◽

2021 ◽

Vol 5 (3) ◽

Author(s):

Feifei Lei ◽

Mingjun Zhao ◽

Haifang Wang ◽

Chao Pan ◽

Xiaoya Shi

Keyword(s):

Heart Failure ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Signaling Pathway ◽

Salvia Miltiorrhiza ◽

Network Pharmacology ◽

Active Components ◽

Radix Astragalus ◽

Pharmacological Studies ◽

Chinese Medicine Treatment

Objective: To explore the target and mechanism of Astragalus membranaceus, poria, salvia miltiorrhiza and semen leiocarpa in the treatment of heart failure by network pharmacology. Methods: The active components of traditional Chinese medicine and the target of heart failure were screened by multi-platform, and the standard gene was transformed by Uniprot. CytoCasp 3.6.1 was used to draw the network diagram of traditional Chinese medicine - component - target. Go and KEGG analysis were performed by Metascape. Results: A total of 36 predictive target sites of Radix Astragalus, Fuling poria, Salvia miltiorrhiza and Draba nemorosa were screened for treatment of heart failure, mainly involving nerve and factor pathways: ADRB2, ADRA1B and AChE. Cancer pathway: TP53, TNF; Pathways of inflammation: IL1B, PTSG2, PTSG1; Sex hormone pathway: ESR1, AR, PGR; Others: SCN5A, HIF1A, etc. The results of GO and KEGG enrichment suggested that the treatment of heart failure with the top four drugs involved cancer pathway, calcium signaling pathway, HIF-1 signaling pathway, and involved in blood circulation, cell proliferation and other processes. Conclusion: This study combines the pharmacological studies of Chinese medicine and western medicine to reveal the mechanism of multi-target and multi-channel regulation of body balance in Chinese medicine treatment.

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A Study on the Mechanism of Milkvetch Root in the Treatment of Diabetic Nephropathy Based on Network Pharmacology

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/6754761 ◽

2020 ◽

Vol 2020 ◽

pp. 1-18

Author(s):

Chunli Piao ◽

Qi Zhang ◽

De Jin ◽

Li Wang ◽

Cheng Tang ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Signaling Pathway ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Systems Pharmacology ◽

Active Components ◽

Kegg Pathways

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. Owing to its complicated pathogenesis, no satisfactory treatment strategies for DN are available. Milkvetch Root is a common traditional Chinese medicine (TCM) and has been extensively used to treat DN in clinical practice in China for many years. However, due to the complexity of botanical ingredients, the exact pharmacological mechanism of Milkvetch Root in treating DN has not been completely elucidated. The aim of this study was to explore the active components and potential mechanism of Milkvetch Root by using a systems pharmacology approach. First, the components and targets of Milkvetch Root were analyzed by using the Traditional Chinese Medicine Systems Pharmacology database. We found the common targets of Milkvetch Root and DN constructed a protein-protein interaction (PPI) network using STRING and screened the key targets via topological analysis. Enrichment of Gene Ontology (GO) pathways and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed. Subsequently, major hubs were identified and imported to the Database for Annotation, Visualization and Integrated Discovery for pathway enrichment analysis. The binding activity and targets of the active components of Milkvetch Root were verified by using the molecular docking software SYBYL. Finally, we found 20 active components in Milkvetch Root. Moreover, the enrichment analysis of GO and KEGG pathways suggested that AGE-RAGE signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway, and TNF signaling pathway might be the key pathways for the treatment of DN; more importantly, 10 putative targets of Milkvetch Root (AKT1, VEGFA, IL-6, PPARG, CCL2, NOS3, SERPINE1, CRP, ICAM1, and SLC2A) were identified to be of great significance in regulating these biological processes and pathways. This study provides an important scientific basis for further elucidating the mechanism of Milkvetch Root in treating DN.

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Using Network Pharmacology to Explore Potential Treatment Mechanism for Coronary Heart Disease Using Chuanxiong and Jiangxiang Essential Oils in Jingzhi Guanxin Prescriptions

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/7631365 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 1

Author(s):

Jia Tai ◽

Junbo Zou ◽

Xiaofei Zhang ◽

Yu Wang ◽

Yulin Liang ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Retinoic Acid ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Essential Oils ◽

Cellular Response ◽

Metabolic Process ◽

Functional Enrichment ◽

Active Components

Background. To predict the active components and potential targets of traditional Chinese medicine and to determine the mechanism behind the curative effect of traditional Chinese medicine, a multitargeted method was used. Jingzhi Guanxin prescriptions expressed a high efficacy for coronary heart disease (CHD) patients of which essential oils from Chuanxiong and Jiangxiang were confirmed to be the most important effective substance. However, the interaction between the active components and the targets for the treatment of CHD has not been clearly explained in previous studies. Materials and Methods. Genes associated with the disease and the treatment strategy were searched from the electronic database and analyzed by Cytoscape (version 3.2.1). Protein-protein interaction network diagram of CHD with Jiangxiang and Chuanxiong essential oils was constructed by Cytoscape. Pathway functional enrichment analysis was executed by clusterProfiler package in R platform. Results. 121 ingredients of Chuanxiong and Jiangxiang essential oils were analyzed, and 393 target genes of the compositions and 912 CHD-related genes were retrieved. 15 coexpression genes were selected, including UGT1A1, DPP4, RXRA, ADH1A, RXRG, UGT1A3, PPARA, TRPC3, CYP1A1, ABCC2, AHR, and ADRA2A. The crucial pathways of occurrence and treatment molecular mechanism of CHD were analyzed, including retinoic acid metabolic process, flavonoid metabolic process, response to xenobiotic stimulus, cellular response to xenobiotic stimulus, cellular response to steroid hormone stimulus, retinoid binding, retinoic acid binding, and monocarboxylic acid binding. Finally, we elucidate the underlying role and mechanism behind these genes in the pathogenesis and treatment of CHD. Conclusions. Generally speaking, the nodes in subnetwork affect the pathological process of CHD, thus indicating the mechanism of Jingzhi Guanxin prescriptions containing Chuanxiong and Jiangxiang essential oils in the treatment of CHD.

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Network pharmacology evaluation of the active ingredients and potential targets of XiaoLuoWan for application to uterine fibroids

Bioscience Reports ◽

10.1042/bsr20202342 ◽

2020 ◽

Vol 40 (12) ◽

Author(s):

Yonghui Yu ◽

Fang Yang ◽

Hong Liu

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Calcium Signaling ◽

Signaling Pathway ◽

Uterine Fibroids ◽

Therapeutic Targets ◽

Network Pharmacology ◽

Therapeutic Effects ◽

Active Ingredients ◽

Calcium Signaling Pathway

Abstract XiaoLuoWan (XLW) is a classical formula in traditional Chinese medicine (TCM) that has satisfactory therapeutic effects for uterine fibroids (UFs). However, its underlying mechanisms remain unclear. To elucidate the pharmacological actions of XLW in treating UFs, an ingredient–target–disease framework was proposed based on network pharmacology strategies. The active ingredients in XLW and their putative targets were obtained from the TCM systems pharmacology database and analysis platform (TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) platforms. The known therapeutic targets of UFs were acquired from the DigSee and DrugBank databases. Then, the links between putative XLW targets and therapeutic UF targets were identified to establish interaction networks by Cytoscape. Finally, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of overlapping gene targets were performed in the STRING database and visualized in R software. In total, 9 active compounds were obtained from 74 ingredients, with 71 curative targets predicted in XLW. Moreover, 321 known therapeutic targets were closely related to UFs, with 29 targets overlapping with XLW and considered interacting genes. Pathway enrichment revealed that the calcium signaling pathway was significantly enriched and the mitogen-activated protein kinase (MAPK) signaling pathway, cAMP signaling pathway, cancer and vascular smooth muscle contraction pathways, cGMP-PKG signaling pathway, and AGE-RAGE signaling pathway were closely associated with XLW intervention for UFs. In conclusion, the network pharmacology detection identified 9 available chemicals as the active ingredients in XLW that may relieve UFs by regulating 29 target genes involved in the calcium signaling pathway, MAPK pathway and cAMP pathway. Network pharmacology analyses may provide more convincing evidence for the investigation of classical TCM prescriptions, such as XLW.

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Revealing mechanism of Caulis Sargentodoxae for the treatment of ulcerative colitis based on network pharmacology approach

Bioscience Reports ◽

10.1042/bsr20204005 ◽

2021 ◽

Vol 41 (1) ◽

Author(s):

Bin Liu ◽

Xin Zheng ◽

Jiajun Li ◽

Xiong Li ◽

Ruimei Wu ◽

...

Keyword(s):

Ulcerative Colitis ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Signaling Pathway ◽

Cellular Response ◽

Akt Signaling ◽

Network Pharmacology ◽

Akt Signaling Pathway ◽

Active Components ◽

Effective Components

Abstract Objective: The traditional Chinese medicine Caulis Sargentodoxae is widely used in the treatment of ulcerative colitis (UC), but the mechanism remains unknown. The present study aims to reveal its effective components, targets and pathways through network pharmacology and bioinformatics approaches. Materials and methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to identify effective components. The ligand-based targets prediction was achieved through SwissTargetPrediction and TargetNet. UC-related targets were identified using Gene Expression Omnibus (GEO) data and DisGeNET. The common targets of disease and components were constructed and analyzed by PPI network. Lastly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses are used to explain the functions of these common targets. Components-Targets-Pathways network was visualized and analyzed to further reveal the connection between the components and targets. Results: Eight active components and 102 key targets were identified to play an important role in UC. These targets were related to regulation of protein serine/threonine kinase activity, positive regulation of cell motility, response to molecule of bacterial origin, response to toxic substance, ERK1 and ERK2 cascade, peptidyl-tyrosine modification, inositol lipid-mediated signaling, cellular response to drug, regulation of inflammatory response and leukocyte migration. Moreover, HIF-1 signaling pathway and PI3K-Akt signaling pathway were the key targets involved in UC-related signaling pathways. Conclusion: The eight active components of Caulis Sargentodoxae mainly play a therapeutic role for UC through synergistic regulation of HIF-1 signaling pathway and PI3K-Akt signaling pathway.

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Study on the Potential Mechanism of Fructus Tribuli in the Treatment of Hypertensive Vascular Remodeling Based on Network Pharmacology and Molecular Docking

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/8862176 ◽

2021 ◽

Vol 2021 ◽

pp. 1-17

Author(s):

Shuyue Wang ◽

Fei Guo ◽

Xiaochen Sun ◽

Xiao Song ◽

Yaohui Yuan ◽

...

Keyword(s):

Molecular Docking ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Signaling Pathway ◽

Vascular Remodeling ◽

Network Pharmacology ◽

Research Approach ◽

Active Components ◽

Active Compounds ◽

Ppi Networks

Background. Hypertensive vascular remodeling (HVR) is the pathophysiological basis of hypertension, which is also an important cause of vascular disease and target organ damage. Treatment with Fructus Tribuli (FT), a traditional Chinese medicine, has a positive effect on HVR. However, the pharmacological mechanisms of FT are still unclear. Therefore, this study aimed to reveal the potential mechanisms involved in the effects of FT on HVR based on network pharmacology and molecular docking. Materials and Methods. We selected the active compounds and targets of FT according to the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Swiss Target Prediction database, and the targets of HVR were collected from the Online Mendelian Inheritance in Man (OMIM), GeneCards, and DrugBank databases. The protein-protein interaction network (PPI) was established using the STRING database. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and network analysis were performed to further explore the potential mechanisms. Finally, molecular docking methods were used to evaluate the affinity between the active compounds and the main target. Results. Seventeen active compounds of FT and 164 potential targets for the treatment of HVR were identified. Component-target and PPI networks were constructed, and 12 main active components and 33 main targets were identified by analyzing the topological parameters. Additionally, GO analysis indicated that the potential targets were enriched in 483 biological processes, 52 cellular components, and 110 molecular functions. KEGG analysis revealed that the potential targets were correlated with 122 pathways, such as the HIF-1 signaling pathway, ErbB signaling pathway, and VEGF signaling pathway. Finally, molecular docking showed that the 12 main active components had a good affinity for the top five main targets. Conclusion. This study demonstrated the multiple compounds, targets, and pathway characteristics of FT in the treatment of HVR. The network pharmacology method provided a novel research approach to analyze potential mechanisms.

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Pharmacological Mechanisms Underlying the Hepatoprotective Effects of Ecliptae herba on Hepatocellular Carcinoma

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/5591402 ◽

2021 ◽

Vol 2021 ◽

pp. 1-17

Author(s):

Botao Pan ◽

Wenxiu Pan ◽

Zheng Lu ◽

Chenglai Xia

Keyword(s):

Hepatocellular Carcinoma ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Signaling Pathway ◽

Akt Signaling ◽

Network Pharmacology ◽

Akt Signaling Pathway ◽

Active Ingredients ◽

Hepatoprotective Effects ◽

Hcc Cells

Background. The number of hepatocellular carcinoma (HCC) cases worldwide has increased significantly. As a traditional Chinese medicine (TCM) with a long history, Ecliptae herba (EH) has been widely used in HCC patients in China, but its hepatoprotective mechanism is still unclear. Methods. In this study, we applied a network pharmacology-based strategy and experimental verification to systematically unravel the underlying mechanisms of EH against HCC. First, six active ingredients of EH were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) by the ADME method. Subsequently, 52 potential targets of 6 active ingredients acting on HCC were screened from various databases, including TCMSP, DGIdb, SwissTargetPrediction, CTD, and GeneCards. Then, by constructing protein-protein interaction (PPI) network from STRING, we displayed the intricate connections among these 52 targets through Cytoscape software. We also applied enrichment analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, to provide an outline and set of concepts for describing gene functions and the advanced functions of biological systems of these 52 targets from genomic and molecular level information. Finally, molecular docking and biological experiments were used to reconfirm these results. Results. We hypothesized that EH might exert anti-HCC activity by acting on hub genes, including RELA, MMP9, PTGS2, ESR1, EGFR, AR, AKT1, HIF1A, AHR, CYP3A4, ABCG2, and MMP2. Moreover, based on GO and KEGG analysis, we speculated that EH may exert hepatoprotective effects on HCC through the following mechanisms: regulation of the PI3K-AKT signaling pathway to promote apoptosis and inhibit the abnormal proliferation of HCC, downregulation of HIF-1A expression by activating the HIF-1 signaling pathway, prevention of HCC by regulating lipid metabolism, and inhibition of nonalcoholic fatty liver disease (NAFLD) by the cytochrome P450 subfamily. Subsequent biological experiments verified that EH inhibits the PI3K-AKT signaling pathway through its active ingredients, quercetin, and wedelolactone, thereby inhibiting the proliferation of HCC cells and promoting the apoptosis of HCC cells. Conclusions. The network pharmacological strategy provides an efficient method to systematically explore the pharmacological mechanism of EH in HCC. Our study demonstrated that the anti-HCC proliferation activity of EH is mainly exerted by two active ingredients (quercetin and wedelolactone), which inhibit the proliferation of HCC cells (HepG2 and Huh-7) by inhibiting PI3K-AKT signaling.

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