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.