| Objective:Literature research and network pharmacology were used to explore the existing drugs for the treatment of CHF by Wen Yang Huo Xue Li Shui,and the potential mechanism of action of Wen Yang Huo Xue Li Shui for the treatment of CHF was explored,which provided support for clinical diagnosis and treatment of diseases and provided a certain reference for subsequent clinical research.Methods:1.The search source was China National Knowledge Infrastructure,Du xiu,Wan fang and China Science and Technology Journal Database,and the literature on the treatment of heart failure by Wen Yang Huo Xue Li Shui collected in each database was searched.The prescriptions in the literature that met the inclusion and exclusion criteria were extracted,the prescription database of Wen Yang Huo Xue Li Shui for CHF treatment was established,and the data were imported into the cloud platform of ancient and modern medical records.The use frequency,attributes(including si qi,wu wei and normalization),association rules,clustering and complex networks of drugs in each prescription were analyzed to obtain the core drugs for the treatment of CHF by Wen Yang Huo Xue Li Shui.2.Conduct network pharmacological analysis on the core drugs obtained in the last step,search the active ingredients and target of the core drugs in related databases,conduct GO enrichment analysis and KEGG enrichment analysis on the obtained compounds,and construct drug-composition-targetpathway and PPI protein interaction network based on Cytoscape platform.And molecular docking authentication.Results:Data mining:1.The top ten traditional Chinese medicines used in the composition of the formula composition of Wen Yang Huo Xue Li Shui method for the treatment of CHF and their average doses were:Indian Buead(178 times,average dose 17.42g),Prepared Common Monkshood Daughter Root(178 times,average dose 11.22g),Milkvetch Root(152 times,average dose 26.34g),Danshen Root Root(147 times,average dose 19.35g),Largehead Atractylodes Rh(141 times,average dose 13.72g),Ramulus Cinnamomi(123 times,average dose 10.76g),Pepperweed Seed(118 times,average dose 14.69g),Radix Glycyrrhizae Preparata(99 times,7.73g),Oriental Waterplantain Rhizome(96 times,average dose 15.02 g),Flos Carthami(74 times,average dose 10.69 g).2.The si qi of the drug in the formula for the treatment of CHF by Wen Yang Huo Xue Li Shui method are mainly warm and flat,followed by mild cold and mild temperature.The highest proportion of the wu wei is sweet,followed by spicy.3.The combination of Wen Yang Huo Xue Li Shui method for the treatment of CHF is mainly based on the lungs,spleen,heart and liver.4.The common drug pairs obtained by the correlation analysis are:Largehead Atractylodes Rh-Indian Buead,Pepperweed Seed-Danshen Root,Milkvetch Root-Pepperweed Seed,Danshen Root-Milkvetch Root,Milkvetch Root-Ramulus Cinnamomi,Ramulus Cinnamomi-Danshen Root,Prepared Common Monkshood Daughter Root-Pepperweed Seed,Prepared Common Monkshood Daughter Root-Danshen Root,Milkvetch Root-Prepared Common Monkshood Daughter Root,Largehead Atractylodes Rh-Prepared Common Monkshood Daughter Root.5.After cluster analysis,three groups of drug combinations were obtained:the first group:Indian Buead,Largehead Atractylodes Rh,Prepared Common Monkshood Daughter Root,Milkvetch Root,Danshen Root;Group 2:Laurel Branch,Bulbophyllum Seed,Oriental Waterplantain Rhizome,Rhizome of Oriental Waterplantain,Motherwort Herb,Ginseng;Group 3:Radix Glycyrrhizae Preparata,Root of Pilose Asiabell,Szechuan Lovage Rhizome,Radix Glycyrrhizae Preparata,Flos Carthami,Paeonia lactiflora,Semen Persicae.6.After complex network analysis,it is concluded that the core drugs for the treatment of CHF by Wen Yang Huo Xue Li Shui method are Prepared Common Monkshood Daughter Root,Indian Buead,Largehead Atractylodes Rh,Pepperweed Seed,Milkvetch Root,Danshen Root Root,Ramulus Cinnamomi.Cyber Pharmacology:1.In the TCMSP database,the active chemical components of a Prepared Common Monkshood Daughter Root,Indian Buead,Largehead Atractylodes Rh,Pepperweed Seed,Milkvetch Root,Danshen Root,Ramulus Cinnamomi.A total of one hundred and fifty-seven chemical components were obtained.There were twenty-one components of Prepared Common Monkshood Daughter Root fifteen components of Indian Buead,seven components of Largehead Atractylodes Rh,twelve components of Pepperweed Seed,twenty components of Milkvetch Root,sixty-five components of Danshen Root and seven components of Ramulus Cinnamomi.2.A total of 1973 disease-related targets were obtained by searching the Gene cards database,and a total of 145 intersection targets between drugs and CHF were obtained.3.Establish PPI network.Eight key proteins were obtained after screening:①AKT1、②IL6、③TNF、④VEGFA、⑤TP53、⑥IL1B、⑦EGFR、⑧MMP9.4.GO enrichment analysis,in which GO BP obtained 865 items,GO CC obtained 95 items,and GO MF obtained 143 items.5.The results of KEGG enrichment analysis showed that the main pathways of the core drugs of the Wen Yang Huo Xue Li Shui method for the treatment of CHF are:AGE-RAGE signaling pathway,cancer signaling pathway,IL-17 signaling pathway,PI3K-Akt signaling pathway,TNF signaling pathway,HIF-1 signaling pathway,FoxO signaling pathway,etc.6.Molecular docking suggests that there is good binding activity between the core chemical components of the core drug and protein of the treatment of CHF by Wen Yang Huo Xue Li Shui;Quercetin binds to IL-6 by forming hydrogen bonds with three amino acids,Asp-34,Gln-175 and Arg179.Quercetin binds to TP53 by forming hydrogen bonds with four amino acids,HIS-233,THR-230,GLU-224 and PRO-222.Quercetin binds to four amino acids,THR-211,SER-205,ASN-204,and ASN-53,and AKT1.Kaempferol binds to AKT1 by binding to three amino acids,SER-205,ASN204 and ASN-53;β-Sitosterol binds to AKT1 by forming hydrogen bonds with two amino acids,ARG-273 and GLU-17;Ivy saponins bind to IL-6 by forming hydrogen bonds with ARG-182;Ivy saponin binds to VEGFA by forming hydrogen bonds with two amino acids,CYS-102 and GLN-22;Ivy saponins bind to AKT1 by forming hydrogen bonds with TYR-315;Isorhamnetin binds to AKT1 by forming hydrogen bonds with VAL-271 and ASN-204.Conclusion(s):1.The WuWei tastes of CHF in the treatment of Wen Yang Huo Xue Li Shui are sweet,sweet and bitter.The property of medicine is warmer and more flat.It involves five viscera,of which the lung,spleen and heart channels are the main channels,followed by the liver and kidney channels.The core drugs of Wen Yang Huo Xue Li Shui therapy for CHF are Prepared Comon Monkshood Daughter Root,Indian Buead,Largehead Atractylodes Rh,Pepperweed Seed,Milkvetch Root,Danshen Root,Ramulus Cinnamomi.2.The core drugs used in the treatment of CHF by Wen Yang Huo Xue Li Shui are mainly composed of quercetin,kaempferol,β-sitosterol,iveigonin,isorhamnetin,etc.It binds with proteins such as AKT1,IL6,TNF,VEGFA,TP53,AGE-RAGE signaling pathway,cancer signaling pathway,IL-17 signaling pathway,PI3K-Akt signaling pathway,TNF signaling pathway,HIF-1 signaling pathway,FoxO signaling pathway and so on to play a therapeutic role in CHF.The mechanisms involved include regulating cell proliferation and apoptosis,gene expression,regulating cell response to estradiol and tumor necrosis factor,lipopolysaccharide and hypoxia and other biological processes,affecting the binding function of heme,RNA polymerase Ⅱ transcription factor activity and other molecular functions to achieve the therapeutic effect of disease.Through molecular docking,it was found that there was a good binding activity between the key chemical components of the core drug of Wen Yang Huo Xue Li Shui in the treatment of CHF.The network pharmacological exploration of this study has a good theoretical basis,which can be further verified by relevant experiments. |
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