This study is to investigate the potential of wolfberry water extracts for the treatment of Alzheimer’s disease (AD) and the relationship between their anti-AD property and the geographic locations in China. Total extracts of all wolfberry samples showed the potent to decrease self-induced A β 1-42 aggregation and Cu 2+ -induced A β 1-42 aggregation and the antioxidant capacity as well as the bioactivity for binding bio-metal. A transgenic drosophila model assay revealed that TE of S1 and S6 (S1-TE and S6-TE) at 100 μg/mL demonstrated the potent rescue effect on memory loss compared to the positive control memantine at 20 μg/mL. Further study also revealed the polysaccharide extracts could contribute to their anti-AD property, and the anti-AD activity conspicuously depends on growing environment. Wolfberry samples S1 and S6 showed much more potent anti-AD property. Meanwhile this study demonstrated that the Chinese commonly consumed wolfberry in boiling water might have the beneficial function to prevent AD pathology.
Yang Xiu,Li Xu,Liu Le,Chen Yuan-Hao,You Yue,Gao Yin,Liu Yue-Ying,Yang Li,Tong Kun,Chen Di-Shi,Hao Jing-Ru,Sun Nan,Zhao Zi-Ming,Gao Can
Alzheimer’s disease (AD) is characterized by aberrant accumulation of extracellular β-amyloid (Aβ) peptides in the brain. Soluble Aβ oligomers are thought to be the most neurotoxic species and are correlated with cognitive dysfunction in early AD. However, there is still no effective treatment so far. We determined that Pep63, a small peptide, had a neuroprotective effect on synaptic plasticity and memory in our previous study. Here, we developed novel and multifunctional liposomes targeting both Aβ oligomers and fibrils based on a liposome delivery system. Transferrin-Pep63-liposomes (Tf-Pep63-Lip), possessing the ability for blood-brain barrier targeting, were also incorporated with phosphatidic acid (PA) and loaded with neuroprotective Pep63. We discovered that administration of Tf-Pep63-Lip could significantly reduce the Aβ burden in the hippocampus, and improve cognitive deficits in 6-month-old APP/PS1 mice in the Morris-Water maze task and fear-conditioning test with the combined effects of PA and Pep63. Tf-Pep63-Lip could capture Aβ oligomers or fibrils and then facilitated microglial chemotaxis nearby for clearance. Simultaneously, Tf-Pep63-Lip hindered Aβ1-42 aggregation and disaggregated Aβ1-42 assembly due to multivalent PA-Aβ. Pep63 effectively inhibited the binding between EphB2 and Aβ oligomers after release from liposomes and rescued NMDA receptors trafficking, the basis of synaptic plasticity. No side effects were observed in either APP/PS1 or wild-type mice, indicating that Tf-Pep63-Lip might be safe under the dosing regimen used in our experiment. Taken together, our results suggested that Tf-Pep63-Lip may serve as a safe and efficient agent for AD combination therapy.
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