期刊
SHOCK
卷 58, 期 5, 页码 457-463出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/SHK.0000000000002001
关键词
Inflammation; apoptosis; myocardial infarction; heart failure; genipin
资金
- Open Project Program of the First Affiliated Hospital of Xinxiang Medical University [XZZX2022007]
- Postgraduate Research and Innovation Support Plan Project of Xinxiang Medical University [YJSCX202170Y]
- Horizontal project of Henan Fangyuan Medical Device Co, Ltd [J00043]
- Natural Science Foundation of Henan Province [202300410311]
This study elucidated the cardioprotective mechanism of genipin and demonstrated its potential for treating ischemic heart failure.
Background and aims: Genipin, an iridoid derived from geniposide by beta-glucosidase hydrolysis, has shown potential benefit in the treatment of heart function insufficiency despite its unclear therapeutic mechanism. This study aimed to investigate the primary cardioprotective mechanism of genipin. We hypothesized that genipin demonstrated the antiapoptosis and anti-inflammation for cardiac protection by inhibiting the cyclooxidase 2 (COX2)-prostaglandin D2 (PGD2) and murine double minute 2 (MDM2)-p53 pathways. Methods: The normal Sprague-Dawley rats were made into myocardial infarction models by conventional methods. Animals were treated with genipin for 5 weeks after myocardial infarction (MI). Morphometric and hemodynamic measurements were performed 5 weeks post-MI. Biological and molecular experiments were performed after the termination. Results: Both morphometry and hemodynamics in systole and diastole were significantly impaired in the model group but restored close to basal level after treatment with genipin. Genipin also restored the post-MI upregulated expressions of cytochrome c, p53, COX2, and PGD2 and downregulated expression of MDM2 to the approximate baseline. Genipin inhibited apoptotic and inflammatory pathways to prevent post-MI structure-function remodeling. Conclusions: This study showed the cardioprotective mechanism of genipin and implied its potential clinical application for the treatment of ischemic heart failure.
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