β-caryophyllene modulates B-cell lymphoma gene-2 family genes and inhibits the intrinsic pathway of apoptosis in isoproterenol-induced myocardial infarcted rats; A molecular mechanism

Abstract

Myocardial infarction (MI) is one of the top causes of morbidity and mortality in the world. Prevention/treatment of MI is of utmost importance. This study planned to appraise the molecular mechanisms of β-caryophyllene on the intrinsic pathway of cardiomyocyte apoptosis in isoproterenol-induced myocardial infarcted rats. Rats were induced MI by isoproterenol (100 mg/kg body weight). The serum cardiac diagnostic markers, heart lipid hydroperoxides, heart lysosomal thiobarbituric acid reactive substances, and serum/heart lysosomal enzymes were considerably (P < 0.05) augmented, while heart antioxidants, heart lysosomal β-glucuronidase and cathepsin-D were considerably (P < 0.05) lessened in isoproterenol-induced myocardial infarcted rats. A reverse transcription-polymerase chain reaction study revealed altered expressions of B-cell lymphoma gene-2, B-cell lymphoma – extra-large, B-cell lymphoma-2 associated-x, and B-cell lymphoma-2 associated death promoter genes. Further, transmission electron microscopic study depicted damaged heart lysosomal structure. Histological study revealed mononuclear cell infiltration and congested dilated blood capillaries in between affected cardiac muscle fibres. Further, 2,3,5-triphenyl tetrazolium chloride staining showed a larger myocardial infarct size. The β-caryophyllene (20 mg/kg body weight) pre-and co-treatment orally, daily, for 21 days considerably (P < 0.05) ameliorated all these altered biochemical, transmission electron microscopic, molecular and histological parameters evaluated in myocardial infarcted rats. Thus, β-caryophyllene inhibited oxidative stress and lysosomal leakage, preserved the heart, and heart lysosomal structure, and prevented the intrinsic pathway of apoptosis. Moreover, it reduced infarct size. The antioxidant effects of β-caryophyllene are the possible mechanism for the observed anti-oxidative stress, anti-lysosomal damage, anti-apoptotic, and myocardial infarct size limiting effects.