ß-caryophyllene blocks reactive oxygen species-mediated hyperlipidemia in isoproterenol-induced myocardial infarcted rats.

Myocardial infarction (MI) is a leading cause of death. Lipid-lowering interventions have been shown to decrease coronary events and mortality of MI and heart failure. In this investigation, we assessed the anti-hyperlipidemic effects of ß-caryophyllene in isoproterenol-induced myocardial infarcted rats. ß-Caryophyllene (20 mg/kg body weight) pre-and co-treatment was given to rats orally, daily, for 3 weeks. Isoproterenol (100 mg/kg body weight) was administered to rats to induce MI. The levels of serum cardiac troponins T and I, serum and heart total cholesterol, triglycerides, free fatty acids, and the levels of serum low-density and very low-density lipoprotein-cholesterols were augmented, and the level of serum high-density lipoprotein-cholesterol was lessened in myocardial infarcted rats. Further, the activity/levels of liver 3-hydroxy-3-methylglutaryl-coenzyme A reductase and plasma thiobarbituric acid reactive substances were amplified and the activity/levels of heart glutathione -S- transferase, vitamin C, and vitamin E were lessened by isoproterenol. A down-regulated expression of liver sterol regulatory element-binding protein-2 and liver low-density lipoprotein-receptor genes was observed by a reverse transcription-polymerase chain reaction study. Moreover, histopathology of Sudan III staining revealed an accumulation of fats in the heart of isoproterenol-induced rats. Nevertheless, ß-caryophyllene pre-and co-treatment blocked alterations in all the parameters examined in isoproterenol-induced rats and inhibited the risk of MI. Moreover, the in vitro study revealed the potent free radical scavenging and antioxidant effects of ß-caryophyllene. ß-Caryophyllene's antioxidant and anti-hyperlipidemic properties are the possible mechanisms for the observed protective effects in this investigation.

Protective effects of ß-caryophyllene on mitochondrial damage and cardiac hypertrophy pathways in isoproterenol-induced myocardial infarcted rats.

The cardiac mitochondrial damage and cardiac hypertrophy pathways are intimately associated with the pathology of myocardial infarction (MI). The protective effects of ß-caryophyllene on mitochondrial damage and cardiac hypertrophy pathways in isoproterenol-induced myocardial infarcted rats were investigated. Isoproterenol (100 mg/kg body weight) was administered to induce MI. The ST-segment, QT interval, and T wave were widened, and the QRS complex and P wave were shortened in the electrocardiogram (ECG) and the serum cardiac diagnostic markers and heart mitochondrial lipid peroxidation products, calcium ions, and reactive oxygen species (ROS) were elevated and the heart mitochondrial antioxidants, tricarboxylic acid cycle, and respiratory chain enzymes were lessened in isoproterenol-induced myocardial infarcted rats. The heart mitochondrial damage was noted in the transmission electron microscopic study. The whole heart weight was increased and the subunits of nicotinamide adenine dinucleotide phosphate - oxidase 2 (Nox 2) genes such as cybb and p22-phox and cardiac hypertrophy genes such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), ß -myosin heavy chain (ß-MHC), and actin alpha skeletal muscle-1(ACTA-1) were highly expressed in the rat's heart by reverse transcription-polymerase chain reaction study. The ß-caryophyllene (20 mg/kg body weight) pre- and co-treatment orally, daily for 21 days reversed changes in ECG and lessened cardiac diagnostic markers, ROS, and whole heart weight and ameliorated mitochondrial damage and Nox/ANP/BNP/ß-MHC/ACTA-1cardiac hypertrophy pathways in isoproterenol-induced myocardial infarcted rats. The observed effects might be due to the antioxidant, anti-mitochondrial damaging, and anti-cardiac hypertrophic mechanisms of ß-caryophyllene.

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.