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α-bisabolol protects against β-adrenergic agonist-induced myocardial infarction in rats by attenuating inflammation, lysosomal dysfunction, NLRP3 inflammasome activation and modulating autophagic flux

Abstract

Emerging evidence demonstrate that NLRP3 inflammasome activation, lysosomal dysfunction, and impaired autophagic flux plays crucial role in the pathophysiology of myocardial infarction (MI). Therapeutic strategies targeting NLRP3 activation, lysosomal enzymes 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 lysosomes dysfunction and autophagic flux can be potential drugs for MI. The present study evaluated the effects and elucidated 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) daily for 10 days along with the subcutaneous injection of ISO (85 mg/kg) at an interval of 24 h for two days (9th and 10th day). ISO injections induced MI as evidenced by elevated cardiac marker enzyme in serum and altered oxidative stress markers in the total heart and lysosomal fractions. ISO also caused activation of NLRP3 inflammasome 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 autophagic mechanism. The findings of the present study clearly demonstrate that α-bisabolol attenuate 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 attributed to its antioxidant, free radical scavenging and anti-inflammatory properties.

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Publication details

The article was received on 13 Mar 2019, accepted on 19 Nov 2019 and first published on 25 Nov 2019


Article type: Paper
DOI: 10.1039/C9FO00530G
Food Funct., 2019, Accepted Manuscript

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    α-bisabolol protects against β-adrenergic agonist-induced myocardial infarction in rats by attenuating inflammation, lysosomal dysfunction, NLRP3 inflammasome activation and modulating autophagic flux

    N. M. Mohamed Fizur, S. Azimullah, F. Laham, S. Tariq, S. Goyal, E. Adeghate and S. Ojha, Food Funct., 2019, Accepted Manuscript , DOI: 10.1039/C9FO00530G

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