期刊
PHYTOMEDICINE
卷 104, 期 -, 页码 -出版社
ELSEVIER GMBH
DOI: 10.1016/j.phymed.2022.154269
关键词
Untargeted metabolomics; Compound Danshen Dripping Pills; Isosorbide 5-mononitrate; Short-and long-term; Acute myocardial infarction; Uric acid
资金
- National Key R&D Program of China [2019YFC1711000]
- National Natural Science Foundation of China [81421005]
The study found that long-term CDDP treatment has prolonged and stable efficacy against AMI. Compared with short-term treatment, it specifically regulates purine and taurine and hypotaurine metabolism and systematically corrects metabolic disorders.
Background: Mild and systematically improving multiple metabolic disorders was a focused view for Compound Danshen Dripping Pills playing synergistic effects through multiple components and multiple targets. The difference in overall therapeutic effects and endogenous metabolic regulation between shortand long-term administration was still unclear.Purpose: This study aimed to explore the difference in endogenous metabolic regulation between shortand longterm Compound Danshen Dripping Pills (CDDP) administration against acute myocardial infarction (AMI). Methods: The model of AMI was induced by ligating the left anterior descending coronary artery. The cardiac protection effects of CDDP were investigated by echocardiography, 1-or 2-week were defined as shortand longterm based on desirable efficacy variability. The entire metabolic changes between shortand long-term administration of CDDP were profiled by UPLC-Q-TOF-MS. In addition, the metabolic regulatory network of CDDP administration against myocardial infarction rats was also compared with those of a typical chemical drug isosorbide 5-mononitrate (ISMN).Results: After 1-or 2-week continuous oral administration, CDDP could significantly alleviate AMI-induced cardiac dysfunction. By using LC-MS-based metabolomics analyses, we systematically investigated the metabolic profiles of plasma and heart tissue samples at fixed exposure time-points (2 h, 24 h) from AMI rats with CDDP treatment. Most interestingly, global endogenous metabolic changes were observed in cardiac samples collected at different stages post consecutive CDDP administration, fluctuating at 2 and 24 h after 1 week but stabilizing after 2 weeks. The disrupted metabolic pathways such as glycerophospholipid, amino acids, fatty acids, and arachidonic acid metabolism were reconstructed after both shortand long-term CDDP treatment, while taurine and hypotaurine metabolism and purine metabolism contributed to the whole efficacy after longterm CDDP administration.Conclusion: Long-term CDDP treatment plays prolonged and stable efficacy against AMI compared with shortterm treatment by specifically regulating purine and taurine and hypotaurine metabolism and systematically redressing metabolic disorders.
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