Bisacurone ameliorates myocardial ischemia/reperfusion injury in rats: regulation of inflammatory and apoptosis pathways via CHOP/GRP78 proteins

Abstract

Background: 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.

Materials and methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Curcuma longa; Apoptosis; Bisacurone; CHOP; GRP78; Myocardial ischemia; cTn-I.