β-Asarone Attenuates Aβ-Induced Neuronal Damage in PC12 Cells Overexpressing APPswe by Restoring Autophagic Flux

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory damage and cognitive dysfunction. Studies have shown that defective autophagic flux is associated with neuronal dysfunction. Modulating autophagic activity represents a potential method of combating AD. In Chinese medicine, Acori Tatarinowii Rhizoma is used to treat dementia and amnesia. β-Asarone, an active component of this rhizome can protect PC12 cells from Aβ-induced injury and modulate expression of autophagy factors. However, its cytoprotective mechanisms have yet to be discerned. It is unclear whether β-asarone affects autophagic flux and, if it does, whether this effect can alleviate Aβ cell damage. In the present study, we constructed APPswe-overexpressing PC12 cell line as a cell model of Aβ-induced damage and assessed expression of autophagic flux-related proteins as well as the number and morphology of autophagosomes and autolysosomes. Our results show that β-asarone decreases the expression levels of Beclin-1, p62, LC3-Ⅱ, and Aβ1-42. β-Asarone reduced the number of autophagosomes and increased the number of autolysosomes, as determined by confocal laser scanning microscopy and transmission electron microscopy. Our results suggest that β-asarone can protect PC12 cells from Aβ-induced damage by promoting autophagic flux, which may be achieved by enhancing autophagosome-lysosome fusion and/or lysosome function.

Aerobic Exercise Alleviates Abnormal Autophagy in Brain Cells of APP/PS1 Mice by Upregulating AdipoR1 Levels

“…In addition, this study found that the LC3-II/I ratio in the brain tissue of wild-type mice was downregulated by aerobic exercise, and the expression of the P62 protein showed a downward trend, but the expression of the P62 mRNA showed an upward trend. Consistently, related studies have shown that drug treatment downregulates cellular LC3-II, p62, and Aβ expression by enhancing lysosomal function, restores autophagic flux, and is associated with TFEB [ 47 , 48 ]. It is suggested that the downregulation of the LC3-II /I ratio and P62 protein level in the brains of wild-type mice and the decrease in the P62 protein levels in the brains of AD mice caused by aerobic exercise may be due to the enhanced lysosomal function that promotes autophagic degradation.…”

Yuan-Zhi decoction in the treatment of Alzheimer’s disease: An integrated approach based on chemical profiling, network pharmacology, molecular docking and experimental evaluation

“…was also used to treat Alzheimer’s disease ( Zhu et al, 2018 ). β -Asarone, a crucial compound of YZD, was reported to prevent amyloid β -induced apoptosis by regulating the PI3K/AKT pathway in PC-12 cells ( Li Z. et al, 2021 ; Meng et al, 2021 ). β -Asarone could also inhibit Amyloid deposition and reverse cognitive deficits in experimental animals ( Wang et al, 2021 ).…”

Potential of food-derived bioactive peptides in alleviation and prevention of Alzheimer's disease

“…Currently, the cell models commonly used to evaluate the neuroprotective efficacy of peptides that can treat AD mainly include the PC12 cell, SH-SY5Y cell, BV-2 microglial cell, hippocampal HT22 cell, and human neuroblastoma cell. [123][124][125][126][127] Some studies have verified that 0.11 mg ml −1 RSH can improve cell viability, alleviate mitochondrial dysfunction, and inhibit apoptosis by using the glutamate-induced PC12 cell model, which further reveals that RSH participates in neuroprotection by regulating the Bax/Bcl-2-related apoptotic pathway, Nrf2-mediated oxidative stress pathway, and CREBrelated neuronal survival pathway. 111 In addition to in vitro studies, animal models and human clinical trials using in vivo experiments are also common.…”