ABSTRACT
To predict the targets of active ingredients of Kuihua Hugan Tablets by network pharmacology, and explore the "multi-component-multi-target-multi-pathway" hepatoprotective mechanism of action. First, through traditional Chinese medicine systems pharmacology(TCMSP) and TCM Database@Taiwan Database, main active ingredients of Kuihua Hugan Tablets were screened out based on oral bioavailability(OB), drug-likeness(DL) and effective half-lives(HL). The targets of active ingredients of Kuihua Hugan Tablets were predicted based on the PharmMapper method. Then, the prediction was conducted by screening the target genes associated with chronic hepatitis and early cirrhosis through CooLGeN and GeneCards databases. Target gene functions and signal pathways were analyzed by bioinformatics annotation database Metascape. Cytoscape software was used to construct the Kuihua Hugan Tablets ingredient-target and ingredient-target-pathway network. String database combined with Cytoscape software was used to construct the networks of component-target and component-target-pathway. STRING database was combined with Cytoscape software to draw protein-protein interaction(PPI) network and conduct network topology analysis. Finally, Systems Dock Web Site software was applied in verifying the molecular docking between active ingredients and potential protein targets. A total of 26 compounds and 509 potential targets were screened out from Kuihua Hugan Tablets in the experiment. The results of PPI network analysis indicated that albumin(ALB), insulin-like growth factor 1(IGF1), matrix metalloproteinase-9(MMP9), matrix metalloproteinase-2(MMP2), non-receptor tyrosine kinase proto-oncogene(SRC), estrogen receptor 1(ESR1) and cancer-signal transduction-inflammation-drugs metabolism-related biological processes and metabolic pathways were closely associated with the active ingredients in Kuihua Hugan Tablets. The effects of Kuihua Hugan Tablets in alleviating chronic hepatitis and early cirrhosis indicated the multi-component, multi-target, and multi-pathway characteristics of traditional Chinese medicines, providing new ideas for further research and development of Kuihua Hugan Tablets.
Subject(s)
Drugs, Chinese Herbal , Pharmacology , Medicine, Chinese Traditional , Metabolic Networks and Pathways , Molecular Docking Simulation , Protein Interaction Mapping , TabletsABSTRACT
OBJECTIVE: To predict the action targets of the hypoglycemic bioactive components of Gegen (Puerariae Lobatae Radix), and investigate the “multi-components, multi-targets and multi-pathways” mechanism. METHODS: Based on the network pharmacology, the reported 27 active ingredients in Gegen were used to predict the action target and reveal the action mechanism via reversed pharmacophore matching method, database mining, and some other methods. The PharmMapper database and DrugBank database were applied to screen the hypoglycemic drug targets approved by FDA. Additionlly, the information of these targets and their intentions were revealed by the String database. At last the ingredients-targets-pathways network was constructed via the Cytoscape software. RESULTS: Studies found that Gegen contained hypoglycemic components, such as:puerarin, 3'-hydroxypuerarin, 3'-methoxypuerarin, daidzein and so on. Their actions involved in 9 potential targets and 25 energy metabolism or signal transmutation relevant biological processes, e.g. insulin receptor, angiotensin-converting enzyme 2 (ACE2), and peroxisome proliferator-activated receptor γ (PPARγ). While the mainly metabolism and signal transmutation pathways were HIF-1 signaling pathway, renin-angiotensin system, FoxO signaling pathway, AMPK signaling pathway and so on. CONCLUSION: From the view of molecular network, this study applied provides network pharmacology methods and technologies to clarify the multi-components, multi-targets and multi-pathways of Gegen on the hypoglycemic effect, and it provides a theoretical basis and a clue for further exploration of the hypoglycemic mechanism of Gegen.
ABSTRACT
Objective To predict the action targets of antitussive and expectorant active ingredients of Farfarae Flos (FF) to understand the “multi-components, multi-targets, and multi-pathways” mechanism. Methods Using network pharmacology, the main components in FF [chlorogenic acid, 3,5-O-dicaffeoylquinic acid, 3,4-O-dicaffeoylquinic acid, 4,5-O-dicaffeoylquinic acid, rutin, caffeic acid, quercetin, kampferol, hyperoside, β-sitosterol, tussilagone, and 7β-(3-Ethyl-ciscrotonoyloxy)-1α-(2-methylbutyryloxy)-3(14)- dehydro-Z-notonipetranone] reported in previous studies, were used to predict the targets of main active ingredients of FF according to the PharmMapper method. The prediction was made by screening of the antitussive and expectorant targets approved by the CooLGeN database and annotating the information of targets with the aid of MAS 3.0 biological molecular function software. Based on the molecular docking, the tight binding of active ingredients with potential protein targets was explored by Systems Dock Web Site. The Cytoscape software was used to construct the FF ingredients-targets-pathways network. Results The network analysis indicated that the active ingredients in FF involve 18 targets, such as IL-2, COX-2, and RNASE3, as well as the signal transduction-inflammation-energy metabolism relevant biological processes and metabolic pathways. Conclusion The antitussive and expectorant effect of FF showed the characteristics of traditional Chinese medicine in multi-components, multi-targets, and multi-pathways. This research provides a scientific basis for elucidation of the antitussive and expectorant pharmacological mechanism of FF.