Liao Xueyan, Wang Qi, Yang Xiaoming, Yao Yuan, Zhu Dezhi, Feng Jing, Wang Kechun
Cardiovascularology, West China School of Public Health, West China Fourth Hospital, Sichuan University, Sichuan, 610041, China.
Department of Laboratory, The Sixth People's Hospital of Chengdu, Chengdu, 610051, China.
BMC Pharmacol Toxicol. 2025 Jun 2;26(1):115. doi: 10.1186/s40360-025-00949-5.
Myocardial infarction is caused by persistent ischemia with or without reperfusion. Bisacurone, a terpenoid present in turmeric, possesses cardioprotective properties that alleviate heart hypertrophy and diabetic cardiomyopathy. However, its effect on myocardial ischemia-reperfusion damage (MIRI) has yet to be evaluated. Thus, the present study aimed to evaluate the underlying cardioprotective mechanism of bisacurone against MIRI in experimental rats.
Male Sprague-Dawley rats (200-220 g) were administered either vehicle, diltiazem (10 mg/kg), or bisacurone (25, 50, and 100 µg/kg) for 14 days, followed by induction of MIRI by partial ligation of the left anterior descending artery and subsequent reperfusion injury.
Bisacurone (50 and 100 µg/kg) significantly (p < 0.05) attenuated IRI-induced cardiac damage, as evidenced by improvements in electrocardiographic, hemodynamic, and left ventricular function tests. Furthermore, cardiac mitochondrial enzyme levels and HO-1 and Bcl-2 mRNA expression were substantially (p < 0.05) upregulated, whereas cardiac oxido-nitrosative stress, ANP, BNP, cTn-I, TNF-α, IL-1, TGF-β, Bax, and caspase-3 mRNA levels were effectively (p < 0.05) downregulated compared to the IRI control. It markedly (p < 0.05) reduced the number of apoptotic cells in cardiac tissue, as determined by flow cytometric analysis. Western blot analysis revealed that bisacurone therapy reduced IRI-induced myocardial apoptosis, as evidenced by a significant (p < 0.05) decrease in CHOP and GRP78-protein expression. Bisacurone also improved IRI-induced histological and ultrastructural aberrations in cardiac tissue.
The findings of this study suggest that bisacurone exerts its cardioprotective effects by inhibiting oxido-nitrosative stress, inflammatory release (TNF-α, IL-1β, and TGF-β), apoptosis (Bax and Caspase-3), and by regulating the expression of CHOP and GRP78.
心肌梗死是由持续性缺血伴或不伴再灌注引起的。姜黄素中的一种萜类化合物双香豆素具有心脏保护特性，可减轻心脏肥大和糖尿病性心肌病。然而，其对心肌缺血再灌注损伤（MIRI）的影响尚未得到评估。因此，本研究旨在评估双香豆素对实验大鼠MIRI的潜在心脏保护机制。
雄性Sprague-Dawley大鼠（200-220克）分别给予溶媒、地尔硫䓬（10毫克/千克）或双香豆素（25、50和100微克/千克），持续14天，随后通过左前降支部分结扎诱导MIRI并进行后续再灌注损伤。
双香豆素（50和100微克/千克）显著（p<0.05）减轻了IRI诱导的心脏损伤，心电图、血流动力学和左心室功能测试的改善证明了这一点。此外，心脏线粒体酶水平以及HO-1和Bcl-2 mRNA表达显著（p<0.05）上调，而与IRI对照组相比，心脏氧化亚硝化应激、ANP、BNP、cTn-I、TNF-α、IL-1、TGF-β、Bax和caspase-3 mRNA水平有效（p<0.05）下调。通过流式细胞术分析确定，它显著（p<0.05）减少了心脏组织中凋亡细胞的数量。蛋白质免疫印迹分析显示，双香豆素治疗减少了IRI诱导的心肌细胞凋亡，CHOP和GRP78蛋白表达显著（p<0.05）降低证明了这一点。双香豆素还改善了IRI诱导的心脏组织组织学和超微结构异常。
本研究结果表明，双香豆素通过抑制氧化亚硝化应激、炎症释放（TNF-α、IL-1β和TGF-β）、细胞凋亡（Bax和Caspase-3）以及调节CHOP和GRP78的表达发挥其心脏保护作用。
