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OBJECTIVE@#To predict the targets and pathways in the therapeutic mechanism of Guizhi Gancao Decoction (GZGCD) against heart failure (HF) based on network pharmacology.@*METHODS@#The chemical components of GZGCD were analyzed using the databases including TCMSP, TCMID and TCM@Taiwan, and the potential targets of GZGCD were predicted using the SwissTargetPrediction database. The targets of HF were obtained using the databases including DisGeNET, Drugbank and TTD. The intersection targets of GZGCD and HF were identified using VENNY. Uniport database was used to convert the information, and the components-targets-disease network was constructed using Cytoscape software. The Bisogene plug-in, Merge plug-in, and CytoNCA plug-in in Cytoscape software were used for protein-protein interaction (PPI) analysis to acquire the core targets. Metascape database was used for GO and KEGG analysis. The results of network pharmacology analysis were verified with Western blot analysis. Three factors (PKCα, ERK1/2 and BCL2) were screened according to the degree value of network pharmacology results and the degree of correlation with heart failure process. The pentobarbtal sodium was dissolvein H9C2 cells treated with serum-free high glucose medium to simulate the ischemic anoxic environment of heart failure. The total proteins of myocardial cells were extracted. The protein contents of PKCα, ERK1/2 and BCL2 were determined.@*RESULTS@#We identified a total of 190 intersection targets between GZGCD and HF using Venny database, involving mainly the circulatory system process, cellular response to nitrogen compounds, cation homeostasis, and regulation of the MAPK cascade. These potential targets were also involved in 38 pathways, including the regulatory pathways in cancer, calcium signal pathway, cGMP-PKG signal pathway, and cAMP signal pathway. Western blot analysis showed that in an in vitro H9C2 cell model of HF, treatment with GZGCD downregulated PKCα and ERK1/2 expressions and upregulated BCL2 expression.@*CONCLUSION@#The therapeutic mechanism of GZGCD for HF involves multiple targets including PRKCA, PRKCB, MAPK1, MAPK3, and MAPK8 and multiple pathways including the regulatory pathway in cancer and the calcium signaling pathway.
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Humanos , Proteína Quinasa C-alfa , Farmacología en Red , Insuficiencia Cardíaca/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-bcl-2RESUMEN
Objective To optimize the alcohol concentration of Guizhi Gancao Decoction extracted by semi-bionic alcoholic extraction (SBAE). Methods Extracts were prepared by the best semi-bionic extraction technology and the best combination method. The contents of Glycyrrhetinic Acid, Cinnamic Acid, total flavones, volatile oil and dry extract in the each extract were determined. Results Comprehensive evaluation Y of 70% alcoholic SBAE extract was significantly higher than that of other alcohol concentration SBAE. Conclusion 70% is the best alcohol concentration of Guizhi Gancao Decoction extracted by SBAE.
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Objective To optimize the best ingredients combination of Guizhi Gancao Decoction. Method The prescription was put into two groups, and extracting by semi-bionic extraction. The contents of Glycyrrhetinic acid, Cinnamic acid, total flavones, volatile oil and dry extract in the each extract were determined, and HPLC fingerprint of the refined by 50% ethanol was compared. Results Except the similar content of dry extract in two kinds of combinations, the other four index components in mixed extract is significantly higher than individual extraction. Two kinds of combinations extract fingerprints of the HPLC had no significant difference. HPLC gradients eluting total score area and main characteristic peak area in mixed extract were higher than individual extraction. Conclusion It is better that Guizhi Gancao Decoction extracted with Guizhi and Gancao mixed.