bisabolol and Myocardial-Infarction

Emerging evidence demonstrates that NLRP3 inflammasome activation, lysosomal dysfunction, and impaired autophagic flux play a crucial role in the pathophysiology of myocardial infarction (MI). Therapeutic strategies targeting NLRP3 activation, lysosomal enzyme release and correcting autophagy have shown beneficial effects in suppressing early inflammatory responses in cardiovascular diseases. Thus, the agents, which inhibit NLRP3 activation and correct lysosome dysfunction and impaired autophagic flux, can be potential drugs for MI. The present study evaluated the effects and elucidated the NLRP3 inflammasome mediated mechanism of α-bisabolol, a dietary sesquiterpene alcohol in a rat model of isoproterenol (ISO)-induced MI. In the present study, male albino Wistar rats were pre- and co-treated with intraperitoneal injection of α-bisabolol (25 mg kg-1) daily for 10 days along with the subcutaneous injection of ISO (85 mg kg-1) at an interval of 24 h for two days (9th and 10th day). ISO injections induced MI as evidenced by the elevated cardiac marker enzyme in serum and altered oxidative stress markers in the total heart and lysosomal fractions. ISO also caused activation of NLRP3 inflammasomes mediating TLR4-NFκB/MAPK signaling pathways and lysosomal dysfunction along with induction and release of proinflammatory cytokines. Interestingly, treatment with α-bisabolol favorably corrected the morphological, histopathological, ultrastructural, biochemical and molecular abnormalities induced by ISO-induced MI in rats. Furthermore, the ultrastructural studies also confirmed the improvement in the autophagic mechanism. The findings of the present study clearly demonstrate that α-bisabolol attenuates oxidative stress and inflammation by inhibiting NLRP3 inflammasome activation and TLR4-NFκB/MAPK signaling pathways along with correcting lysosomal dysfunction and impaired autophagic flux. The underlying pharmacological and molecular mechanism of cardioprotection was attributed to its antioxidant, free radical scavenging and anti-inflammatory properties.

Topics: Adrenergic beta-Agonists; Animals; Anti-Inflammatory Agents; Antioxidants; Autophagy; Inflammasomes; Inflammation; Male; Monocyclic Sesquiterpenes; Myocardial Infarction; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Protective Agents; Rats; Rats, Wistar; Toll-Like Receptor 4

Mitochondrial dysfunction plays crucial role in the pathologenesis of myocardial infarction (MI). The present study evaluated the protective effect of α-bisabolol against isoproterenol (ISO)-induced mitochondrial dysfunction and apoptosis in rats. Male albino Wistar rats were pre- and co-treated with intraperitoneal injection of α-bisabolol (25 mg/kg body weight) daily for 10 days. To induce experimental MI, ISO (85 mg/kg body weight) was injected subcutaneously to the rats at an interval of 24 h for 2 days (9th and 10th day). ISO-induced MI was indicated by the decreased activities of heart creatine kinase and lactate dehydrogenase in rats. ISO administration also enhanced the concentrations of heart mitochondrial lipid peroxidation products and decreased the activities/concentrations of mitochondrial antioxidants, Kreb's cycle dehydrogenases and mitochondrial electron transport chain complexes I, II + III and IV in rats. Furthermore, ISO triggers calcium overload and ATP depletion in the rat's heart mitochondria followed by the mitochondrial cytochrome-C release and the activation of intrinsic pathway of apoptosis by upregulating the myocardial pro-apoptotic Bax, P

Topics: Animals; Apoptosis; Isoproterenol; Male; Mitochondria, Heart; Mitochondrial Proteins; Monocyclic Sesquiterpenes; Muscle Proteins; Myocardial Infarction; Rats; Rats, Wistar; Sesquiterpenes

The effect of α-bisabolol on hemodyanimcs, lipid peroxidation, and nonenzymatic antioxidants was evaluated in isoproterenol-induced myocardial infarction in rats. They were pre- and cotreated with α-bisabolol (25 mg/kg body weight) daily for 10 days along with the subcutaneous injection of isoproterenol (85 mg/kg body weight) at an interval of 24 hours for 2 days (9th and 10th days). Increased activities of serum creatine kinase and creatine kinase-MB along with altered levels/concentrations of lipid peroxidation products and nonenzymatic status were observed in the plasma and heart tissues of rats. Treatment with α-bisabolol showed protective effects by reversing the altered biochemical parameters and hemodynamics studied. The in vitro reducing power of α-bisabolol confirmed its potent antioxidant action. These biochemical benefits were translated into functional recovery by the maintenance of the hemodynamics in rats. The findings showed that α-bisabolol has the potential to protect against isoproterenol-induced myocardial infarction due to its potent antilipid peroxidation and antioxidant properties.

Topics: Adrenergic beta-Agonists; Animals; Antioxidants; Creatine Kinase; Creatine Kinase, MB Form; Hemodynamics; In Vitro Techniques; Isoproterenol; Lipid Peroxidation; Male; Monocyclic Sesquiterpenes; Myocardial Infarction; Oxidative Stress; Rats, Wistar; Sesquiterpenes