Astragalin actives autophagy and inhibits apoptosis of astrocytes in AD mice via down-regulating Fas/Fasl-VDAC1 pathway

Abstract

Alzheimer's disease (AD) as a common neurodegenerative disease, which characterized by amyloid Aβ deposition and neurofibrillary tangles. Astragalin (AST), a natural flavonoid, has anti-inflammatory, antioxidant, anti-cancer, and other pharmacological effects. Astrocytes can phagocytize and degrade Aβ in their vicinity. In this study, we used the AD mice model established by injecting the mixture of Aβ1-42 and Aβ25-35 into the CA1 region of the hippocampus, and C8D1A cells injured by Aβ1-42 to explore the neuroprotective effects of AST. Our findings showed that AST enhances learning and cognitive ability of AD mice, reduces Aβ deposition and neurofibrillary tangles in the brain, and improves the structural morphology of hippocampal nerve cells. Furthermore, AST promoted autophagy and suppressed apoptosis of astrocytes in the AD model. Additionally, AST inhibited the expression of proteins associated with the Fas/Fasl-VDAC1 signaling pathway, while autophagy inhibitor chloroquine (CQ) or apoptosis agonist phenoxodiol reversed above change. Interestingly, consistent with the action of pathway Fas inhibitor KR-33493, AST could activate autophagy of Aβ1-42 injured C8D1A cells while inhibit their apoptosis. In conclusion, AST activated autophagy and inhibited apoptosis of hippocampal astrocytes in AD mice, ameliorating animal cognitive deficits by down-regulating Fas/Fasl-VDAC1 signaling pathway. Thus, this study provided a new perspective and experimental foundation for developing AD treatment drugs.