Euxanthone improves cognitive impairment by attenuating mitochondrial fragmentation and suppressing oxidative stress

Mitophagy and Apoptosis significantly contribute to the dynamics of mitochondria and their associated disorders. Euxanthone (EUX) is a xanthone derivative that exhibits several therapeutic effects at a preclinical level. However, its impact in a cerebral ischemia and reperfusion model has not been investigated. The investigation aimed to determine the protective effect of EUX in cerebral ischemia and cognitive impairment and explore its underlying mechanism. A bilateral common carotid artery occlusion (BCCAO) model was employed in the present work. Forty male ICR mice were divided into four groups - Sham, BCCAO, EUX30 (BCCAO + EUX 30 mg/kg) and EUX60 (BCCAO + EUX 60 mg/kg). The mice were then subjected to a Morris water maze study for investigation of learning and memorizing capabilities. The hippocampal specimens of mice were quantified for the presence of oxidative markers. Homogenized hippocampal fractions were determined for the levels of Beclin-1, LC3, p53, Bax, Caspase-3, Bnip3, DRP1 and Nrf2. The present investigation revealed that BCCAO caused oxidative stress in mitochondria and led to mitochondrial breakdown. EUX administration markedly attenuated BCCAO triggered mitochondrial stress and related breakdown. EUX treatment normalized Bnip3, Beclin1, Pink1, Parkin, p53, Bax, Caspase-3, and LC3 II/I. Altogether, EUX treatment modulated Mitophagy and Apoptosis induced by mitochondrial stress mediated by mitochondrial fragmentation, due to cerebral ischemia and reperfusion injury.

cerebral ischemia; cognitive impairment; euxanthone; mitophagy; reperfusion injury.