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In searching for a promising candidate for treatment of Alzheimer’s disease (AD), the effects of ethanol extract (CE) and defatted ethanol extract (dCE) of Durio zibithinus cultivar “Mon Thong” on pathological cascade of AD were investigated by in vitro and cell culture models. The results exhibited that both of CE and dCE extracts could inhibit acetylcholinesterase function in bioautography assay. For thioflavin T assay which studies an effect on beta-amyloid (Aβ) aggregation indicated that both CE and dCE at the concentration of 10 mg/mL were able to inhibit Aβ aggregation with inhibitory percentage values of 44.96±3.50 and 36.91±5.50, respectively. From the neuroprotection study in cell culture revealed that both CE and dCE could reduce human neuroblastoma cell (SH-SY5Y) death induced by Aβ. Moreover, the result from Western blotting analysis indicated that CE inhibited Aβ- induced cell death via DR5 inhibition, resulting in inhibiting of cleave-caspase 8, cleave-caspase 3 activation and changing in the phosphorylation level of Akt (protein kinase B). The overall results indicated that the Durio zibithinus extract possesses multimode of action involved with AD pathology cascade including anti-Aβ aggregation, acetylcholinesterase inhibition, and neuroprotection against β-amyloid. Thus, the Durio zibithinus cultivar “Mon Thong” might be a potential candidate for further developing as a functional food or a drug for Alzheimer’s disease.
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