Cui Ying, Wu Jianfa, Wang Yanfang, Li Dan, Zhang Furui, Jin Xiaoman, Li Meihui, Zhang Jing, Liu Zhi
College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.
College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; Jilin Provincial International Joint Research Center for the Development and Utilization of Authentic Medicinal Materials, Changchun 130118, China.
Phytomedicine. 2024 Jul;129:155637. doi: 10.1016/j.phymed.2024.155637. Epub 2024 Apr 15.
Ginsenoside F (GF) serves as the principal intestinal metabolite resulting from the oral intake of Panax ginseng and Panax quinquefolius, exhibiting antioxidative, hypolipidemic, antitumor, and anti-inflammatory properties. Nevertheless, its effect on myocardial infarction (MI) is still unknown.
The purpose of this study is to investigate the protective effect and the underlying mechanisms of GF against isoproterenol (ISO)-induced MI.
ISO-induced H9c2 cardiomyocytes and MI rat models were utilized as in vitro and in vivo models to evaluate the impact of anti-MI of GF. The underlying mechanisms were investigated using a variety of methodologies, including electrocardiography, Western blot analysis, histopathological examination, immunofluorescence, immunohistochemistry, and ELISA techniques.
In vivo experiments, our results indicated that GF significantly ameliorated ISO-induced electrocardiographic (ECG) abnormalities, myocardial fiber necrosis, rupture, fibrosis of myocardial tissues, and suppressed cardiac enzyme activities. Meanwhile, GF notably raised the activity of antioxidant enzymes like CAT, GSH, and SOD. Furthermore, it downregulated Keap1 expression level while upregulating NQO1, Nrf2, and HO-1 expression levels. Additionally, GF suppressed the expression of the cleaved caspase-3 and pro-apoptotic protein Bax while promoting the expression of anti-apoptotic proteins Bcl-2, p-PI3K, and p-Akt. TUNEL fluorescence results also demonstrated that GF effectively inhibited cardiomyocyte apoptosis. Furthermore, consistent with the results of animal experiments, GF considerably attenuated ROS generation, changed apoptosis and mitochondrial function, and reduced oxidative stress in ISO-induced H9c2 cardiomyocytes through activating Nrf2/HO-1 and PI3K/Akt signaling pathways.
Taken together, GF ameliorated MI by preventing cardiocyte apoptosis, oxidative stress, and mitochondrial dysfunction via modulating the Nrf2/HO-1 and PI3K/Akt signaling pathways, showing potential as a treatment strategy for treating MI.
人参皂苷F（GF）是口服人参和西洋参后在肠道产生的主要代谢产物，具有抗氧化、降血脂、抗肿瘤和抗炎特性。然而，其对心肌梗死（MI）的影响仍不清楚。
本研究旨在探讨GF对异丙肾上腺素（ISO）诱导的心肌梗死的保护作用及其潜在机制。
采用ISO诱导的H9c2心肌细胞和心肌梗死大鼠模型作为体外和体内模型，评估GF抗心肌梗死的作用。使用多种方法研究其潜在机制，包括心电图、蛋白质免疫印迹分析、组织病理学检查、免疫荧光、免疫组织化学和酶联免疫吸附测定技术。
在体内实验中，我们的结果表明，GF显著改善了ISO诱导的心电图（ECG）异常、心肌纤维坏死、破裂、心肌组织纤维化，并抑制了心肌酶活性。同时，GF显著提高了CAT、GSH和SOD等抗氧化酶的活性。此外，它下调了Keap1的表达水平，同时上调了NQO1、Nrf2和HO-1的表达水平。此外，GF抑制了裂解的caspase-3和促凋亡蛋白Bax的表达，同时促进了抗凋亡蛋白Bcl-2、p-PI3K和p-Akt的表达。TUNEL荧光结果也表明，GF有效抑制了心肌细胞凋亡。此外，与动物实验结果一致，GF通过激活Nrf2/HO-1和PI3K/Akt信号通路，显著减轻了ISO诱导的H9c2心肌细胞中活性氧的产生，改变了细胞凋亡和线粒体功能，并降低了氧化应激。
综上所述，GF通过调节Nrf2/HO-1和PI3K/Akt信号通路，防止心肌细胞凋亡、氧化应激和线粒体功能障碍，从而改善心肌梗死，显示出作为治疗心肌梗死的潜在治疗策略。
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