Abstract
β-Asarone is the main constituent of Acorus tatarinowii Schott and exhibits important effects in diseases such as neurodegenerative and neurovascular diseases. Icariin (ICA) is a major active ingredient of Epimedium that has attracted increasing attention because of its unique pharmacological effects in degenerative disease. In this paper, we primarily explored the effects of the combination of β-asarone and ICA in clearing noxious proteins and reversing cognitive deficits. The accumulation of damaged mitochondria and mitophagy are hallmarks of aging and age-related neurodegeneration, including Alzheimer's disease (AD). Here, we provide evidence that autophagy/mitophagy is impaired in the hippocampus of APP/PS1 mice and in Aβ1-42-induced PC12 cell models. Enhanced mitophagic activity has been reported to promote Aβ and tau clearance in in vitro and in vivo models. Meanwhile, there is growing evidence that treatment of AD should be preceded by intervention before the formation of pathological products. The efficacy of the combination therapy was better than that of the individual therapies applied separately. Then, we found that the combination therapy also inhibited cell and mitochondrial damage by inducing autophagy/mitophagy. These findings suggest that impaired removal of defective mitochondria is a pivotal event in AD pathogenesis, and that combination treatment with mitophagy inducers represents a potential strategy for therapeutic intervention.
Highlights
Introduction βAsarone (1,2,4-trimethoxy-5-[(Z)-prop-1-enyl]benzene) is an essential component of Acorus tatarinowii Schott volatile oil that can pass through the blood-brain barrier
To uncover the cellular and molecular causes of mitochondrial impairment and the accumulation of damaged mitochondria in Alzheimer’s disease (AD), we examined the changes in mitochondria in the hippocampus of APP/PS1 mice and in the PC12 cell model
Combined with the results of our previously published articles, we have demonstrated that autophagy is inhibited in these AD models, but we need to systematically examine the protein levels of major factors involved in mitochondrial metabolism and mitophagy
Summary
Asarone (1,2,4-trimethoxy-5-[(Z)-prop-1-enyl]benzene) is an essential component of Acorus tatarinowii Schott volatile oil that can pass through the blood-brain barrier. Our group has been working on β-asarone for nearly 30 years, and we found that it has a very good pharmacodynamic effect in AD. This monomer improved the behavioural symptoms of Alzheimer’s rats and improved learning and memory abilities by inhibiting the PI3K/Akt/mTOR pathway [1–3]. We treated Aβ42-induced PC12 cells with Icariin and β-asarone at gradient concentrations. By exploring the effects of drug concentration and combination treatment, we found that the combination treatment had better therapeutic outcomes than the individual treatments [6]. Just like a blood pressure medication that combines calcium channel blockers with diuretics
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