| Abstrakt: |
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 p450 1A1 (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. [ABSTRACT FROM AUTHOR] |
