Aim This work is to provide a network approach to identify the potential therapeutic targets in molecular level for xuefu-zhuyu decoction （XZD） and gualou-xiebai-banxia decoction （GXBD） in treating Coronary artery...Aim This work is to provide a network approach to identify the potential therapeutic targets in molecular level for xuefu-zhuyu decoction （XZD） and gualou-xiebai-banxia decoction （GXBD） in treating Coronary artery dis- ease （CAD）. Methods The networks between the ingredients/drugs and relevant target proteins for XZD, GXBD, and modern anti-CAD drugs were constructed, respectively. A master network based on the three established networks was further generated. By comparing the similarities and the differences of the targets containing in the master net- work between the individual formula and the modern drugs, the potential anti-CAD targets for XZD and GXBD were i- dentified for further pharmacological investigations. Results Although the herbal formulations and the chemical con- stituents of XZD and GXBD were significant different, both formulas presented the great similarity on target proteins and with the Tanimoto coefficient of 0. 7225. Comparison the formula-specific targets to modem drugs targets, 50 mu- tual targets with higher possibility were modulated. Moreover, a total amount of 114 mutual targets between formulas derived from the master network were identified to be not yet related to those of the approved anti-CAD drugs. Among them, the top 10 targets were identified to be NOS3, PTPN1, GABRA1, PRKACA, CDK2, MAOB, ESR1, ADH1C, ADH1B and AKR1B1. The formula-specific targets of XZD or GXBD which were not yet covered by the current anti- CAD drugs provided the potential opportunities to discovery of the new drug candidates from the two formulas for CAD treatment. Conclusion The established method of network analysis provides a novel approach for screening of the potential therapeutic targets based on the chemical constituents in traditional Chinese medicines or formulas. It is cru- cial for this work to select relatively favorable therapeutic areas of traditional Chinese medicines, syndrome-oriented formulas and syndrome differentiation of same diseases. Meanwhile, this kind of work is helpful for unveiling the mo- lecular mechanism of TCM formulas.展开更多
Gualou-Xiebai-Banxia decoction has a long history of medical use for treating cardiovascular diseases in China.In this study,we investigated the protective effect and underlying mechanisms GXB in typeⅡdiabetes with a...Gualou-Xiebai-Banxia decoction has a long history of medical use for treating cardiovascular diseases in China.In this study,we investigated the protective effect and underlying mechanisms GXB in typeⅡdiabetes with acute myocardial ischemia(T2DM-AMI)rats.We hypothesized that GXB may display its protective effect on T2DM-AMI by reducing endothelial progenitor cells(EPCs)apoptosis via activating PI3K(phosphatidyl inositol 3-kinase)/Akt(serine/threonine protein kinase B)/e NOS(endothelial nitric oxide synthase)signaling.Rats were challenged with a high-fat diet and intraperitoneal injection of streptozotocin to induce a model of typeⅡdiabetes mellitus(T2DM)and coronary ligation to induce acute myocardial infarction(AMI).Changes in metabolites were assessed via enzyme-linked immunoassay and biochemical examination.The number and apoptosis rate of EPCs in peripheral blood were detected by flow cytometry.Target m RNAs and proteins in EPCs were analyzed by RT-PCR and Western blot analysis.The results demonstrated that GXB treatment decreased T2DM-AMI-associated changes in plasma fasting blood glucose,muscular enzymes,and blood lipids,and reduced oxidative stress.Furthermore,EPC apoptosis was increased in T2DM-AMI rats and was associated with decreased m RNA and protein levels of PI3K,Akt,and eNOS compared to the controls.Conversely,T2DM-AMI rats treated with GXB exhibited more circulating EPCs and downregulated levels of cell apoptosis,combined with increased m RNA and protein levels of PI3 K,Akt,and eNOS compared to those of untreated T2DM-AMI rats.Our study showed that GXB treatment mitigated EPC apoptosis and promoted PI3K/Akt/eNOS signaling in T2DM-AMI rats.展开更多
文摘Aim This work is to provide a network approach to identify the potential therapeutic targets in molecular level for xuefu-zhuyu decoction （XZD） and gualou-xiebai-banxia decoction （GXBD） in treating Coronary artery dis- ease （CAD）. Methods The networks between the ingredients/drugs and relevant target proteins for XZD, GXBD, and modern anti-CAD drugs were constructed, respectively. A master network based on the three established networks was further generated. By comparing the similarities and the differences of the targets containing in the master net- work between the individual formula and the modern drugs, the potential anti-CAD targets for XZD and GXBD were i- dentified for further pharmacological investigations. Results Although the herbal formulations and the chemical con- stituents of XZD and GXBD were significant different, both formulas presented the great similarity on target proteins and with the Tanimoto coefficient of 0. 7225. Comparison the formula-specific targets to modem drugs targets, 50 mu- tual targets with higher possibility were modulated. Moreover, a total amount of 114 mutual targets between formulas derived from the master network were identified to be not yet related to those of the approved anti-CAD drugs. Among them, the top 10 targets were identified to be NOS3, PTPN1, GABRA1, PRKACA, CDK2, MAOB, ESR1, ADH1C, ADH1B and AKR1B1. The formula-specific targets of XZD or GXBD which were not yet covered by the current anti- CAD drugs provided the potential opportunities to discovery of the new drug candidates from the two formulas for CAD treatment. Conclusion The established method of network analysis provides a novel approach for screening of the potential therapeutic targets based on the chemical constituents in traditional Chinese medicines or formulas. It is cru- cial for this work to select relatively favorable therapeutic areas of traditional Chinese medicines, syndrome-oriented formulas and syndrome differentiation of same diseases. Meanwhile, this kind of work is helpful for unveiling the mo- lecular mechanism of TCM formulas.
基金supported by the National Natural Science Foundation of China(Nos.81173164 and 81573852)the Public Service Key Project of Shandong Provincial Research and Development(No.2018GSF119009)。
文摘Gualou-Xiebai-Banxia decoction has a long history of medical use for treating cardiovascular diseases in China.In this study,we investigated the protective effect and underlying mechanisms GXB in typeⅡdiabetes with acute myocardial ischemia(T2DM-AMI)rats.We hypothesized that GXB may display its protective effect on T2DM-AMI by reducing endothelial progenitor cells(EPCs)apoptosis via activating PI3K(phosphatidyl inositol 3-kinase)/Akt(serine/threonine protein kinase B)/e NOS(endothelial nitric oxide synthase)signaling.Rats were challenged with a high-fat diet and intraperitoneal injection of streptozotocin to induce a model of typeⅡdiabetes mellitus(T2DM)and coronary ligation to induce acute myocardial infarction(AMI).Changes in metabolites were assessed via enzyme-linked immunoassay and biochemical examination.The number and apoptosis rate of EPCs in peripheral blood were detected by flow cytometry.Target m RNAs and proteins in EPCs were analyzed by RT-PCR and Western blot analysis.The results demonstrated that GXB treatment decreased T2DM-AMI-associated changes in plasma fasting blood glucose,muscular enzymes,and blood lipids,and reduced oxidative stress.Furthermore,EPC apoptosis was increased in T2DM-AMI rats and was associated with decreased m RNA and protein levels of PI3K,Akt,and eNOS compared to the controls.Conversely,T2DM-AMI rats treated with GXB exhibited more circulating EPCs and downregulated levels of cell apoptosis,combined with increased m RNA and protein levels of PI3 K,Akt,and eNOS compared to those of untreated T2DM-AMI rats.Our study showed that GXB treatment mitigated EPC apoptosis and promoted PI3K/Akt/eNOS signaling in T2DM-AMI rats.
