Background:Shenzao dripping pill(SZDP)is empirically prescribed for treating cardiac diseases.Nevertheless,there is a lack of comprehensive knowledge regarding the underlying mechanisms contributing to its therapeutic...Background:Shenzao dripping pill(SZDP)is empirically prescribed for treating cardiac diseases.Nevertheless,there is a lack of comprehensive knowledge regarding the underlying mechanisms contributing to its therapeutic effects.The objective of this study is to investigate the underlying mechanism of SZDP against chronic myocardial ischemia(CMI)in a rat model.Methods:In this study,we utilized electrocardiographic and echocardiographic detection along with pathological tissue analysis to evaluate the efficacy of SZDP.The integration of network pharmacology and metabolomics was conducted to investigate the mechanisms.Molecular docking and molecular dynamics simulations were used to validate the binding energy between the compounds of SZDP and the associated targets.Results:The results showed that SZDP was able to improve T wave voltage,reverse CMI abnormalities in ejection fraction and fractional shortening,and restore histopathological heart damage.Metabolomics results indicated that disturbances of metabolic profile in CMI rats were partly corrected after SZDP administration,mainly affecting purine metabolism.13-Docosenamide may be the potential metabolic biomarker of the therapeutic application of SZDP for CMI.Integrating network pharmacology and metabolomics,thiopurine S-methyltransferase(TPMT),xanthine dehydrogenase/oxidase(XDH),bifunctional purine biosynthesis protein ATIC(ATIC),and cytochrome p4501A1(CYP1A1)were identified as possible targets of SZDP to exert therapeutic effects by enhancing the metabolic levels of L-Tryptophan,Deoxyribose 1-phosphate and Phosphoribosyl formamidocarboxamide.Conclusion:SZDP has a therapeutic effect on CMI by regulating metabolite levels,acting on the targets of TMPT,XDH,ATIC,and CYP1A1,and reducing cardiomyocyte injury and myocardial fibrosis.展开更多
Background:Shenzao dripping pills(SZDP)is an empirical prescription of traditional Chinese medicine that is mainly used to treat coronary heart disease.However,the chemical composition and pharmacological mechanisms o...Background:Shenzao dripping pills(SZDP)is an empirical prescription of traditional Chinese medicine that is mainly used to treat coronary heart disease.However,the chemical composition and pharmacological mechanisms of SZDP are unknown.Methods:In this study,ultra-high performance liquid chromatography-quadruple-Exactive Orbitrap mass spectrometry was used to identify the chemical components in extracts and medicated plasma of SZDP.Subsequently,we performed network pharmacology methods,including target prediction by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine,protein-protein interaction network via STRING database;further,the key targets and compounds were screened using Cytoscape.Finally,the key targets and compounds were validated by molecular docking.Results:72 chemical constituents were identified from SZDP by high performance liquid chromatography and mass spectrometry technology.Among the components absorbed into plasma by SZDP,24 prototype components and 9 metabolized components were identified.The network pharmacology analysis of the prototype components showed that there are 13 key compounds(including ginsenoside Rc,Rb1,Rb2,ferulic acid,etc.),90 proteins(including proto-oncogene tyrosine-protein kinase Src,nuclear receptor subfamily 3 group C member 1,caspase-3,etc.),and 10 pathways(including estrogen,IL-17 and VEGF signaling pathway,etc.)that play an essential role in the treatment of coronary heart disease with SZDP.In addition,the results of molecular docking revealed that ginsenosides Rc,Rb2 and Rb1 have strong binding activities to the caspase-3,as well as ginsenoside Rb2 to the nuclear receptor subfamily 3 group C member 1.Conclusion:This study showed that SZDP might act through multiple chemical constituents and targets against coronary heart disease.展开更多
目的探讨参藻合剂对2型糖尿病大鼠糖脂代谢水平的影响。方法采用高糖高脂饲料结合链脲佐菌素制备2型糖尿病大鼠模型,建模成功后随机分为模型组,罗格列酮组(2 mg·kg^(-1)),参藻合剂低、中、高剂量组(2.5,5,10 m L·kg^(-1)),每...目的探讨参藻合剂对2型糖尿病大鼠糖脂代谢水平的影响。方法采用高糖高脂饲料结合链脲佐菌素制备2型糖尿病大鼠模型,建模成功后随机分为模型组,罗格列酮组(2 mg·kg^(-1)),参藻合剂低、中、高剂量组(2.5,5,10 m L·kg^(-1)),每组12只。给药4周后,观察参藻合剂对2型糖尿病大鼠24 h摄食、饮水及尿量的影响,检测糖化血红蛋白及肝糖原含量,全自动生化仪检测血清中TG及HDL-C含量,并观察其对胰腺及肾组织病理形态的影响。结果与模型组比较,参藻合剂中、高剂量组大鼠24 h饮水量、肝糖原含量显著降低(P<0.05);高剂量组大鼠24 h摄食量显著降低(P<0.05);中剂量组HDL-C显著升高(P<0.05);各剂量组大鼠糖化血红蛋白及TG含量均显著降低(P<0.01),胰腺及肾组织的病理形态显著改善。结论参藻合剂对2型糖尿病大鼠糖脂代谢具有显著的调节改善作用。展开更多
基金funded by Scientific and Technological Planning Project of Guangzhou City(Grant No.201803010115)Projects of The National Natural Science Foundation of China(Grant No.82173972)+1 种基金2021 Traditional Chinese Medicine(Medicine of South China)Industry Talents Project-Innovation Team of South China Medicine Resources,Guangdong Provincial Basic and Applied Basic Research Fund(Grant No.2023A1515011147)supported by the Key Unit of Chinese Medicine Digitalization Quality Evaluation of State Administration of Traditional Chinese Medicine.
文摘Background:Shenzao dripping pill(SZDP)is empirically prescribed for treating cardiac diseases.Nevertheless,there is a lack of comprehensive knowledge regarding the underlying mechanisms contributing to its therapeutic effects.The objective of this study is to investigate the underlying mechanism of SZDP against chronic myocardial ischemia(CMI)in a rat model.Methods:In this study,we utilized electrocardiographic and echocardiographic detection along with pathological tissue analysis to evaluate the efficacy of SZDP.The integration of network pharmacology and metabolomics was conducted to investigate the mechanisms.Molecular docking and molecular dynamics simulations were used to validate the binding energy between the compounds of SZDP and the associated targets.Results:The results showed that SZDP was able to improve T wave voltage,reverse CMI abnormalities in ejection fraction and fractional shortening,and restore histopathological heart damage.Metabolomics results indicated that disturbances of metabolic profile in CMI rats were partly corrected after SZDP administration,mainly affecting purine metabolism.13-Docosenamide may be the potential metabolic biomarker of the therapeutic application of SZDP for CMI.Integrating network pharmacology and metabolomics,thiopurine S-methyltransferase(TPMT),xanthine dehydrogenase/oxidase(XDH),bifunctional purine biosynthesis protein ATIC(ATIC),and cytochrome p4501A1(CYP1A1)were identified as possible targets of SZDP to exert therapeutic effects by enhancing the metabolic levels of L-Tryptophan,Deoxyribose 1-phosphate and Phosphoribosyl formamidocarboxamide.Conclusion:SZDP has a therapeutic effect on CMI by regulating metabolite levels,acting on the targets of TMPT,XDH,ATIC,and CYP1A1,and reducing cardiomyocyte injury and myocardial fibrosis.
基金supported by the Project of the Science and Technology Plan Project of Guangzhou(No.201803010115)the National Natural Science Foundation of China(No.82173972)the National Major“Significant New Drugs Development”during the Thirteenth Five-Year Plan Period(No.2017ZX09301077).
文摘Background:Shenzao dripping pills(SZDP)is an empirical prescription of traditional Chinese medicine that is mainly used to treat coronary heart disease.However,the chemical composition and pharmacological mechanisms of SZDP are unknown.Methods:In this study,ultra-high performance liquid chromatography-quadruple-Exactive Orbitrap mass spectrometry was used to identify the chemical components in extracts and medicated plasma of SZDP.Subsequently,we performed network pharmacology methods,including target prediction by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine,protein-protein interaction network via STRING database;further,the key targets and compounds were screened using Cytoscape.Finally,the key targets and compounds were validated by molecular docking.Results:72 chemical constituents were identified from SZDP by high performance liquid chromatography and mass spectrometry technology.Among the components absorbed into plasma by SZDP,24 prototype components and 9 metabolized components were identified.The network pharmacology analysis of the prototype components showed that there are 13 key compounds(including ginsenoside Rc,Rb1,Rb2,ferulic acid,etc.),90 proteins(including proto-oncogene tyrosine-protein kinase Src,nuclear receptor subfamily 3 group C member 1,caspase-3,etc.),and 10 pathways(including estrogen,IL-17 and VEGF signaling pathway,etc.)that play an essential role in the treatment of coronary heart disease with SZDP.In addition,the results of molecular docking revealed that ginsenosides Rc,Rb2 and Rb1 have strong binding activities to the caspase-3,as well as ginsenoside Rb2 to the nuclear receptor subfamily 3 group C member 1.Conclusion:This study showed that SZDP might act through multiple chemical constituents and targets against coronary heart disease.
