Integrated network pharmacology and metabolomics to explore the mechanisms of Shenzao dripping pill against chronic myocardial ischemia  

作　　者：Jie-Hui Kuang Tao Hu Lu-Yong Zhang Yu-Feng Yao Ming-Hua Xian Shu-Mei Wang 

机构地区：[1]School of Chinese Materia Medica,Guangdong Pharmaceutical University,Guangzhou 510006,China [2]Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou 510006,China [3]Engineering&Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province,Guangdong Pharmaceutical University,Guangzhou 510006,China [4]Guangzhou Key Laboratory of Construction and Application of New Drug Screening Model Systems,Guangdong Pharmaceutical University,Guangzhou 510006,China [5]Traditional Chinese Medicine Resource Germplasm Bank Management Center,Yunfu 527500,China.

出　　处：《Traditional Medicine Research》2024年第11期12-26,共15页TMR传统医学研究

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);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.

摘　　要：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.

关 键 词：chronic myocardial ischemia metabolomics network pharmacology serum metabolites Shenzao dripping pill 

分 类 号：R542.2[医药卫生—心血管疾病]