Methanol extract from miracle fruit seeds mitigates Alzheimer's disease and enhance autophagy via suppressing the AKT/mTOR signal pathway.

Background

Alzheimer's disease (AD) is a neurodegenerative disease. In previous study, we discovered that methanol extract of miracle fruits seeds (MFSs) had a therapeutic effect on AD model mice.

Objective

In this research, we aimed to study the role of MFSs in alleviating amyloid-β (Aβ) deposition and further explore the possible mechanism of action of MFSs.

Methods

We used behavioral tests and various immunolabeling techniques on two AD model (Aβ transgenic model strain CL4176 of Caenorhabditis elegans and the 3 × Tg-AD mice).

Results

In CL4176, MFSs (10 μg/mL) could effectively alleviate the paralysis caused by Aβ, the Aβ plaques were significantly reduced, the transcription levels of Aβ, age-1, akt-1 and mTOR genes were significantly downregulated, and the transcription of autophagy-related gene lgg-1 was enhanced. The cognitive function of mice in the MFSs group was improved, which was related to reduced synapse loss and Aβ-positive neurons in the brain. Meanwhile, the transcription levels of amyloid-β protein precursor (AβPP), Tau, Akt and mTOR were significantly reduced. The protein expressions of PSD95, SYN1, LC3II/I and Beclin-1 were significantly increased, and the value of p62/SQSTM1, p-AKT/AKT, p-mTOR/mTOR were reduced.

Conclusions

MFSs significantly alleviates Aβ deposition in CL4176 and mice. The mechanism by which it improves cognitive function in AD mice may be related to enhanced autophagy regulated by the Akt/mTOR signaling pathway.