A network pharmacology approach to investigate the mechanism of Shuxuening injection in the treatment of ischemic stroke

Cui, Qian; Zhang, Yuliang; Ma, Yuhui; Yu, Haoyu; Zhao, Xin-Zhe; Zhang, Lihui; Ge, Shaoqin; Zhang, Guowei; Qin, Xiude

doi:10.1016/j.jep.2020.112891

Cited by 75 publications

(52 citation statements)

References 42 publications

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“…erefore, we believed that PTEC could treat IS with a scientific basis [39,44]. Some of the main target genes (ESR1 and RELA) were also found from Precursors works [29,34]. An association between variation in the estrogen receptor-alpha gene (ESR1) and cerebrovascular disease is related to gender [45].…”

Section: Discussionmentioning

confidence: 99%

Systematic Investigation of the Effect of Powerful Tianma Eucommia Capsule on Ischemic Stroke Using Network Pharmacology

Feng

Huang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Ischemic stroke (IS) is a serious disease with a high rate of death and disability, and a growing number of people are becoming victims. Existing drugs not only have limited therapeutic effects but also have obvious side effects. Most importantly, drug resistance due to long-term or improper use of drugs is detrimental to patients. Therefore, it is urgent to find some alternative or supplementary medicines to alleviate the current embarrassment. Powerful Tianma Eucommia Capsule (PTEC) is mainly used to treat IS in China for thousands of years; however, the molecular mechanism is not clear. Methods. Pharmacology ingredients and target genes were filtered and downloaded from websites. A pharmacology ingredient-target gene network was constructed to predict the molecular interactions between ingredients and target genes. Enrichment analysis was performed to explore the possible signal pathways. LeDock was used to simulate the interaction form between proteins and main active ingredients and to deduce key amino acid positions. Results. Two hundred eighty-nine target genes and seventy-four pharmacological ingredients were obtained from public databases. Several key ingredients (quercetin, kaempferol, and stigmasterol) and primary core target genes (PTGS1, NCOA2, and PRSS1) were detected through ingredient-target gene network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis demonstrated that ingredients affect networks mainly in nuclear receptor activity and G protein-coupled amine receptor activity; besides, fluid shear stress and atherosclerosis, human cytomegalovirus infection, and hepatitis B signaling pathways might be the principal therapy ways. A series of presumed key amino acid sites (189ASP, 190SER, 192GLN, 57HIS, and 99TYE) were calculated in PRSS1. Six of the target genes were differentially expressed between male and female patients. Conclusions. Seven new putative target genes (ACHE, ADRA1A, AR, CHRM3, F7, GABRA1, and PRSS1) were observed in this work. Based on the result of GO and KEGG analysis, this work will be helpful to further demonstrate the molecular mechanism of PTEC treatment of IS.

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Section: Discussionmentioning

confidence: 99%

Systematic Investigation of the Effect of Powerful Tianma Eucommia Capsule on Ischemic Stroke Using Network Pharmacology

Feng

Huang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…Therefore, it is speculated that AA and other compounds in YZG act on the CASP3 gene to treat dysfunctional uterine bleeding through the apoptosis pathway. CASP3 gene balances apoptosis and proliferation, improves the cell cycle, and regulates the normal and cyclic growth, proliferation, and apoptosis of endometrial tissues, which impels the endometrium to shed completely and stops bleeding in time [50].…”

Section: Discussionmentioning

confidence: 99%

Dissecting the mechanism of Yuzhi Zhixue granule on ovulatory dysfunctional uterine bleeding by network pharmacology and molecular docking

Luo

Liu

et al. 2020

Chin Med

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Background Yuzhi Zhixue Granule (YZG) is a traditional Chinese patent medicine for treating excessive menstrual flow caused by ovulatory dysfunctional uterine bleeding (ODUB) accompanied by heat syndrome. However, the underlying molecular mechanisms, potential targets, and active ingredients of this prescription are still unknown. Therefore, it is imperative to explore the molecular mechanism of YZG. Methods The active compounds in YZG were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The putative targets of YZG were collected via TCMSP and Search Tool for Interacting Chemicals (STITCH) databases. The Therapeutic Target Database (TTD) and Pharmacogenomics Knowledgebase (PharmGKB) databases were used to identify the therapeutic targets of ODUB. A protein–protein interaction (PPI) network containing both the putative targets of YZG and known therapeutic targets of ODUB was built. Furthermore, bioinformatics resources from the database for annotation, visualization and integrated discovery (DAVID) were utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking was performed to verify the binding effect between the YZG screened compounds and potential therapeutic target molecules. Results The study employed a network pharmacology method, mainly containing target prediction, network construction, functional enrichment analysis, and molecular docking to systematically research the mechanisms of YZG in treating ODUB. The putative targets of YZG that treat ODUB mainly involved PTGS1, PTGS2, ALOX5, CASP3, LTA4H, F7 and F10. The functional enrichment analysis suggested that the produced therapeutic effect of YZG against ODUB is mediated by synergistical regulation of several biological pathways, including apoptosis arachidonic acid (AA) metabolism, serotonergic synapse, complement and coagulation cascades and C-type lectin receptor signaling pathways. Molecular docking simulation revealed good binding affinity of the seven putative targets with the corresponding compounds. Conclusion This novel and scientific network pharmacology-based study holistically elucidated the basic pharmacological effects and the underlying mechanisms of YZG in the treatment of ODUB.

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“…For example, as an important member of AP-1 transcription factor family, JUN is involved in growth, metastasis, and drug resistance of cancer [42]. PTGS2 is also known as cyclooxygenase-2 (COX-2), and Cox-2 is a ratelimiting enzyme that regulates prostaglandin synthesis during arachidonic acid metabolism and is mainly involved in various in ammatory reactions of the body [43]. In addition, PTGS2 can activate nuclear factor kappa B (NF -κB) signaling pathway and reduce DNA damage after radiotherapy [44].…”

Section: Discussionmentioning

confidence: 99%

Exploring Molecular Mechanism of Traditional Chinese Medicine Euphorbiae Semen on Reversing of Multidrug Resistance in Leukemia Based on Network Pharmacology Strategy and Molecular Docking Technology

Song

Guo

Sun

et al. 2020

Preprint

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Background: Leukemia was listed by the World Health Organization as one of the five most intractable diseases in the world. The multi-drug resistance (MDR) of leukemia cells limits the efficacy of anti-tumor drugs and is the major reason for the chemotherapy failure and recurrence of leukemia chemotherapy. Some studies have shown that Euphorbiae semen (ES) possesses the characteristics of new therapeutic drugs for MDR. However, the molecular mechanisms and active compounds have not yet been fully clarified. Therefore, there is a need for explore its active compounds and demonstrate its mechanisms through network pharmacology and molecular docking technology.Method: First, the TCMSP database was searched and screened the active compounds of the ES, supplemented with compounds verified by literature, so as to further identify the core compounds in the active ingredient. Simultaneously, the TCMSP and Swiss database were searched to the targets of active compounds, and the targets of reverses leukemia multidrug resistance (RL-MDR) were screened in the relevant databases, such as GeneCards and DrugBank. Then, the targets of active compounds were intersected with RL-MDR targets to obtain potential targets of ES acting on MDR. The compound–target network was constructed by Cytoscape. The target protein–protein interaction network was built using STRING and Cytoscape database. Second, the R language and DAVID database were used to analyse Gene Ontology (GO) biological functions analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathways enrichment. Finally, molecular docking method was utilized to investigate the binding activity between the core targets and the active compounds of ES.Results: Compound–target network mainly contained 22 compounds and 81 corresponding targets. Finally, seven components in ES were selected and 10 core targets were identified; Key targets contained JUN, CASP3, MAOA, AR, PPARG, DRD2, ADRA2A, CHRM2, PTGS2 and MAPK14. GO enrichment analysis indicated the main biological functions of potential genes of ES in the treatment of MDR. KEGG pathway enrichment analysis showed the main pathways, mainly including apoptosis, pathways in cancer, p53 signaling pathway, VEGF signaling pathway, TNF signaling pathway and PI3K–Akt signaling pathway. Finally, we chose the top 10 common targets for molecular docking with the 7 active compounds of ES. The results of molecular docking indicated that the compounds of ES, which had good affinity with targets. Conclusion: The molecular mechanism of ES in the treatment of MDR showed the synergistic reaction of multi-compound, multi-target, and multi-pathway of traditional Chinese medicine, which provided ideas for further clinical research.

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A network pharmacology approach to investigate the mechanism of Shuxuening injection in the treatment of ischemic stroke

Cited by 75 publications

References 42 publications

Systematic Investigation of the Effect of Powerful Tianma Eucommia Capsule on Ischemic Stroke Using Network Pharmacology

Systematic Investigation of the Effect of Powerful Tianma Eucommia Capsule on Ischemic Stroke Using Network Pharmacology

Dissecting the mechanism of Yuzhi Zhixue granule on ovulatory dysfunctional uterine bleeding by network pharmacology and molecular docking

Exploring Molecular Mechanism of Traditional Chinese Medicine Euphorbiae Semen on Reversing of Multidrug Resistance in Leukemia Based on Network Pharmacology Strategy and Molecular Docking Technology

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