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Mechanism of Yiqi Huoxue Compound for Treatment of Acute Myocardial Infarction Based on Network Pharmacology

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Mechanism of Yiqi Huoxue Compound for Treatment of Acute Myocardial Infarction Based on Network Pharmacology Revista Argentina de Clínica Psicológica 2020, Vol. XXIX, N°4, 851-863 851 DOI: 10.24205/03276716.2020.892 Mechanism of Yiqi Huoxue Compound for Treatment of Acute Myocardial Infarction Based on Network Pharmacology ZhiXian Wanga,DiChi Jianga,XiaoJu Wangb, JinQian Wangc,GuoHeng Hud* ABSTRACT Objective: To explore the potential mechanism of Yiqi Huoxue Compound for the treatment of acute myocardial infarction (AMI) through network pharmacology. Methods: The main active compounds and related effect targets of Yiqi Huoxue Compound were searched and screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The standard names of effect targets were obtained using Uniprot database, the disease-related targets were obtained using GeneCards, Online Mendelian Inheritance in Man (OMIM) and A Database of Gene- Disease Associations (DisGeNET), and the protein interaction network of AMI-related core targets was constructed through STRING database and Cytoscape software. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for core targets using R language software. Results: Based on the screening conditions, 93 effective compounds, 140 drug targets of Yiqi Huoxue Compound and 71 potential therapeutic targets related to AMI were obtained. A total of 92 entries were excavated by GO enrichment analysis (P<0.05), and 42 pathways related to AMI were screened out by KEGG pathway enrichment analysis (P<0.05). Conclusion: Yiqi Huoxue Compound contains a variety of active compounds, which can exert its therapeutic effect through multiple targets and multiple signaling pathways. The research results can provide a modern theoretical basis for the clinical application and mechanism research of Yiqi Huoxue Compound. KEYWORDS: Yiqi Huoxue Compound; acute myocardial infarction; network pharmacology INTRODUCTION multi-level network to analyse active compounds AMI is one of the common coronary and potential drugs goals, disease targets and arteriosclerotic types (CADs), which for a variety of target genotypes is established in a new discipline reasons consist of sudden severe stenosis or a full with a view to analysing and predicting potential coronary artery occlusion. The development and mechanisms for medical use in disease from a occurrence mechanisms of AMI have still not been holistic point of view fully clarified. The main mechanisms of current Recent studies have demonstrated that research are the creation, activation of leukocytes traditional Chinese medicine, one of AMI therapy and calcium excess[1], of oxygen-free radicals. A and research entries, has a certain protective effect on AMI. In the TCM categories AMI is one among a Deapartment of Graduate School, Hunan University of Chinese the 'heavy duty,' 'cold-mouth pain' and 'angel Medicine,China b Department of International Medical,The First Affiliated Hospital of pectoris.' The heart is the location of the disease, Hunan University of Chinese Medicine,China including spleen, liver and kidneys. AMI causes qi cMedical Innovation Experimental Center, The First Affiliated Hospital of Hunan University of Chinese Medicine,China and blood deficiency, yin-yang and visceral dDepartment of Neurology, The First Affiliated Hospital of Hunan dysfunction, including a stagnation of qi, blood University of Chinese Medicine,China stages, turbid plexemia and cold congestion. *Corresponding Author: GuoHeng Hu Address: Xiangxing College, Hunan University of Traditional Chinese Asthenia is the main aetiology in blood vessel and Medicine, 113 Shaoshan Middle Road, Yuhua District, Changsha City, surface stasis. In combination with my own Hunan Province,China Email: [email protected] experience, my supervisors have done this to treat REVISTA ARGENTINA 2020, Vol. XXIX, N°4, 851-863 DE CLÍNICA PSICOLÓGICA 852 ZhiXian Wang, DiChi Jiang, XiaoJu Wang, JinQian Wang, GuoHeng Hu AMI with excellent clinical effectiveness by way of on the compounds involved with the active long-term clinical practise. ingredients of Yiqi Huoxue Compound. My supervisor, Professor Guoheng Hu, is the instructor of inheriting academic experience of the Establishment of drug target network for Yiqi sixth batch of nationally renowned experts in TCM, Huoxue Compound and he has been engaged in clinical work for Using the Uniport data base decades and achieved great accomplishments in (https:/www.uniprot.org/) the objective protein the field of cardiovascular and cerebrovascular obtained has been converted and corrected to diseases. He has discovered in the clinical obtain the Yiqi Huoxue composition effect targets. treatment of CAD that based on the etiology of The MCT and its impact targets were then imported asthenia in origin and excess in superficiality, the for visualisation into the software Cytoscape compound method should be used in the (http:/www.cytoscape.org/) and the appropriate treatment, thereby tonifying qi and activating blood drug target network was built. circulation. Simply tonifying qi cannot dissipate blood stasis, while simply activating blood Collection of AMI-related targets circulation cannot invigorate qi. Therefore, In the Human Gene database (GeneCards- tonifying qi and activating blood circulation should https:/www.genecards.org), online Mendelian be combined, and qi can promote blood circulation, heritage at man (OMIM-https:/www.omim.org/) remove stasis, benefit pulse and eliminate and in a data base of gene-disorders assocations, stagnation. Therefore, the experiential prescription the keyword was the "acute myocardial infarction." Yiqi Huoxue Compound tonifying qi and activating AMI related targets have been searched. AMI- blood circulation was prepared to invigorate qi and related targets were searched. The targets for dredge pulse vessel. Astragalus membranaceus is disease were achieved after deduplication. used as the sovereign drug to promote blood The drug targets and disease targets were circulation through strengthening qi. Angelica mapped through Venny 2.1.0 sinensis is used as the ministerial drug to replenish (http://bioinfogp.cnb.sic.es/tools/venny/index.ht blood and promote blood circulation through ml). The target intersection was displayed in the "removing extravasated blood and nourishing new form of Venn diagram, based on which the blood". Salvia miltiorrhiza is used to "eliminate potential therapeutic targets of Yiqi Huoxue stagnant blood, and replenish new blood", and Compound in the treatment of AMI were obtained. remove blood stasis. Moreover, Ligusticum wallichii, as a drug promoting circulation and Establishment of protein-protein interaction (PPI) regulating vital energy, can dredge blood vessels, network and screening of core targets invigorate blood circulation, and activate meridians The potential therapeutic targets obtained were to stop pain. entered into the Search Tool for the Retrieval of The potential mechanism of Yiqi Huoxue Interacting Genes/Proteins (STRING-https://string- Compound in the treatment of AMI was explored db.org/) to get the information about protein through a network of pharmacology to provide a interaction. Then the target protein intersection new theoretical basis for the prevention and obtained was imported into Cytoscape software for treatment of cardiovascular diseases with TCM. visualization, the protein interaction network diagram was plotted, the TCM-disease protein MATERIALS AND METHODS interaction visual network was constructed, and the Screening of active ingredients and prediction of core targets were screened. targets in Yiqi Huoxue Compound In the research of the key wording of the active Gene Ontology (GO) enrichment analysis and ingredient in the Yiqi Huoxue compound the Kyoto Encyclopedia of Genes and Genomes (KEGG) traditional Pharmacological Database and Analysis pathway analysis Platform (TCMSP) for Chinese drugs systems, The information about TCM-disease targets "Astragalus membranaceus," "Angelica sinensis," obtained above was calculated using the R language "Ligusticum wallichii" and "Salvia Miltiorrhiza." The software, and the results of GO enrichment analysis active ingredients of the Yiqi HuoXue Compound and KEGG pathway analysis were obtained. Then were tested according to the pharmacokinetic the results were presented in the form of bar principle using the built-in TCMSP Ingredient Scrub graphs or bubble graphs. Tool which used to screen off and create a Database RESULTS REVISTA ARGENTINA 2020, Vol. XXIX, N°4, 851-863 DE CLÍNICA PSICOLÓGICA 853 ZhiXian Wang, DiChi Jiang, XiaoJu Wang, JinQian Wang, GuoHeng Hu Screened active ingredients in Yiqi Huoxue 20 GO entries in a bar and a bubble diagram Compound (Figures 4 and 5) were excavated. Table 4. Protease OB≥30% and DL≥0.18 were set as the Binding, serine hydrolase activity, heme binding, conditional parameters, based on which the active binding of tetrapyrrol, serine endopeptidase ingredients of Yiqi Huoxue Compound were activity, serine peptidase activity, integrate binding, screened out through TCMSP. A total of 94 active growth factor receptor binding and binding RNA compounds were screened out, including 20 in A. Polymerase II transcript factors have been enriched membranaceus, 2 in A. sinensis, 7 in L. wallichii and with the GO entries. The KEGG enrichment analysis 65 in S. miltiorrhiza. After deduplication, the unique (P<0.05) screened 42 signalling paths and the top value 93 was retained (Table 1). 20 entries were drawn into bars and bubble charts (figures
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