Zhao Liang, Sun Lulu, Li Xiafei, Lu Tian, Pan Yuxue, Du Pengchong
College of Life Science and Technology, First Affiliated Hospital, Xinxiang Medical University, Xinxiang, China.
College of Medical Engineering, Xinxiang Medical University, Xinxiang, China.
Shock. 2022 Nov 1;58(5):457-463. doi: 10.1097/SHK.0000000000002001. Epub 2022 Oct 3.
Background and aims: Genipin, an iridoid derived from geniposide by β-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.
京尼平是一种由栀子苷经β - 葡萄糖苷酶水解得到的环烯醚萜类化合物，尽管其治疗机制尚不清楚，但已显示出在治疗心功能不全方面的潜在益处。本研究旨在探讨京尼平的主要心脏保护机制。我们假设京尼平通过抑制环氧化酶2（COX2）-前列腺素D2（PGD2）和鼠双微体2（MDM2）-p53信号通路发挥抗凋亡和抗炎作用，从而保护心脏。方法：采用常规方法将正常的Sprague-Dawley大鼠制成心肌梗死模型。心肌梗死后，动物接受京尼平治疗5周。在心肌梗死后5周进行形态学和血流动力学测量。实验结束后进行生物学和分子实验。结果：模型组在收缩期和舒张期的形态学和血流动力学均显著受损，但经京尼平治疗后恢复至接近基础水平。京尼平还使心肌梗死后上调的细胞色素c、p53、COX2和PGD2的表达恢复，并使MDM2的表达下调至接近基线水平。京尼平抑制凋亡和炎症信号通路，以防止心肌梗死后的结构 - 功能重塑。结论：本研究揭示了京尼平的心脏保护机制，并暗示其在治疗缺血性心力衰竭方面的潜在临床应用价值。
