ß-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.

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 ß-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 ß-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 ß-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, ß-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 ß-caryophyllene are the possible mechanism for the observed anti-oxidative stress, anti-lysosomal damage, anti-apoptotic, and myocardial infarct size limiting effects.

ß-Caryophyllene inhibits Fas- receptor and caspase-mediated apoptosis signaling pathway and endothelial dysfunction in experimental myocardial infarction.

We planned to appraise the effects of ß-caryophyllene on Fas- receptor and caspase-mediated apoptosis signaling pathway and endothelial dysfunction in rats infarcted with isoproterenol. Rats were induced myocardial infarction by using isoproterenol (100 mg/kg body weight [b.w]). Serum creatine kinase-MB, serum cardiac troponin-T, heart weight, heart rate, and heart lipid peroxidation were greatly (p < 0.05) augmented, while heart enzymatic antioxidants and plasma nonenzymatic antioxidants were greatly (p < 0.05) lessened in isoproterenol-treated rats. Reverse transcription-polymerase chain reaction study revealed augmented expressions of Fas-receptor and caspases 8, 9, and 3 genes in myocardial infarcted rats. Furthermore, iNOS protein expression was amplified and eNOS protein was lessened in the myocardial infarcted heart. Three weeks pre- and cotreatment with ß-caryophyllene (20 mg/kg b.w) greatly (p < 0.05) protected isoproterenol-treated rats against these altered structural, biochemical, molecular, and immunohistochemical parameters, by its anti-cardiac hypertrophic, anti-tachycardial, antioxidant, anti-apoptotic, and anti-endothelial dysfunction effects. In conclusion, these findings projected the use of ß-caryophyllene for the therapy of human myocardial infarction after clinical trials.