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Musk Tongxin Dripping Pills for treating Ticagrelor in Patients After Percutaneous Coronary Intervention: Echocardiography Combined with Untargeted Metabolomics

ABSTRACT: Objectives: As current clinical practice guidelines, ticagrelor is the suggested therapeutic scheme to prevent adverse cardiovascular events in acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI) treatment. However, this therapeutic strategy still fails, and around 30% patients display inadequate antiplatelet responses. Musk Tongxin Dripping Pill (MTDP) in Chinese hospital was usually considered as the combination with ticagrelor to improve the treatment effect. Unfortunately, the mechanism has not been elucidated. Methods: The untargeted metabolomic method was introduced based on liquid chromatography–high-resolution mass spectrometry (HPLC-HRMS) coupled with STI for the research of the drug combination mechanism between ticagrelor and MTDP. 28 patients with a confirmed diagnosis of AMI were selectively collected, who were then divided into two different dosage regimen groups, and the serum samples were collected for the untargeted metabolomics assay. Then the differential metabolites were associated with blood biochemical indicators. Results: The GLS values in both groups increased after treatment and those in the ticagrelor and MTDP combination group after treatment were higher than those in the ticagrelor group (p < 0.05), suggesting that the combination medication has better therapeutic effect on patients with myocardial infarction. From metabolomics analysis, the species of metabolites changed in two groups before and after treatment. Moreover, 93 differential metabolites changed in the drug combination group compared with the ticagrelor group after treatment (p < 0.05), which mainly related to changes in fatty acid metabolism pathways. Then the differential metabolites were found to be related with blood biochemical indicators, such as lipid, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Conclusion: This work will provide a possible mechanism of the drug combination interaction between ticagrelor and MTDP from two angles of echocardiography and metabonomics. Several potential metabolic pathways were also found to have a relationship with MTDP, which will provide a new perspective in clinical medication.

SUBMITTER: Nan L

PROVIDER: S-EPMC8579064 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Heart failure (HF), the final stage of cardiovascular diseases, is a clinical syndrome of cardiac structural or functional abnormalities. QiShenYiQi Dripping Pills (T101), short for QSYQ (T101), showed effectiveness and safety in the treatment of HF according to modern pharmacological research and clinical studies, but the mechanism remains unclear. This study aims to clarify the mechanism of QSYQ (T101) in treating heart failure through the analysis to critical biomarkers, targets and pathways. Materials and Methods: In this study, the efficacies of QSYQ (T101) in non-human primates and rodents were evaluated, and the mechanism was demonstrated by integrating network pharmacology and metabolomics analysis. Furthermore, the targets from network pharmacology and the metabolites from targeted metabolomics were jointly analyzed to screen the critical pathways. Results: In rhesus monkeys with spontaneous chronic heart failure, nasogastric administration of QSYQ (T101) for 12 weeks caused profound improvement of systolic and diastolic function as evidenced by echocardiography detection. Consistently, QSYQ (T101) administration especially with higher dose lowered the blood pressure and improved the ventricular remodeling, collagen deposition and fibrosis markedly in Spontaneous Hypertension Rats (SHR) model. Computational prediction showed that QSYQ (T101) exhibited anti-HF effects possibly through HIF-1 signaling pathway, FoxO signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway and other enriched paths. Metabolomics analysis obtained 23 significantly altered metabolites, revealing that QSYQ (T101) significantly regulated the abnormal levels of fatty acids, carnitines, organic acids pyridines, nucleosides, which were mostly involved in myocardial energy metabolism related pathways. Conclusion: Based on serum and myocardium metabolomics and network pharmacology, the present study revealed that the actions of QSYQ (T101) in treating HF depend on multi-components, multi-targets and multi-pathways.

Project description:QiShenYiQi dripping pills (QSYQ), a traditional Chinese medicine, are commonly used to treat coronary heart disease, and QSYQ was recently approved as a complementary treatment for ischemic heart failure in China. However, only few studies reported on whether QSYQ exerts a protective effect on heart failure induced by pressure overload. In this study, we explored the role of QSYQ in a mouse model of heart failure induced by transverse aortic constriction (TAC). Twenty-eight C57BL/6J mice were divided into four groups: Sham + NS group, Sham + QSYQ group, TAC + NS group, and TAC + QSYQ group. QSYQ dissolved in normal saline (NS) was administered intragastrically (3.5 mg/100 g/day) in the Sham + QSYQ and TAC + QSYQ groups. In the Sham + NS and TAC + NS groups, NS was provided every day intragastrically. Eight weeks after TAC, echocardiography, and cardiac catheterization were performed to evaluate the cardiac function, and immunofluorescent staining with anti-actinin2 antibody was performed to determine the structure of the myocardial fibers. Moreover, TUNEL staining and Masson trichrome staining were employed to assess the effects of QSYQ on cardiac apoptosis and cardiac fibrosis. Western blots and real-time polymerase chain reaction (PCR) were used to measure the expression levels of vascular endothelial growth factor (VEGF) in the heart, and immunohistochemical staining with anti-CD31 antibody was performed to explore the role of QSYQ in cardiac angiogenesis. Results showed that TAC-induced cardiac dysfunction and disrupted structure of myocardial fibers significantly improved after QSYQ treatment. Moreover, QSYQ treatment also significantly improved cardiac apoptosis and cardiac fibrosis in TAC-induced heart failure, which was accompanied by an increase in VEGF expression levels and maintenance of microvessel density in the heart. In conclusion, QSYQ exerts a protective effect on TAC-induced heart failure, which could be attributed to enhanced cardiac angiogenesis, which is closely related to QSYQ. Thus, QSYQ may be a promising traditional Chinese medicine for the treatment of heart failure induced by pressure overload such as hypertension.

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Musk Tongxin Dripping Pills for treating Ticagrelor in Patients After Percutaneous Coronary Intervention: Echocardiography Combined with Untargeted Metabolomics

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