Effects of Dendrotrophe umbellate (Blume) Miq. MeOH Extracts on Acetylcholinesterase Activity and APP-related Protein Metabolism

Alzheimer's disease (AD) is the most common form of progressive neurodegenerative disease in the elderly and is characterized by memory and cognitive impairments. In patients with AD, memory and cognitive decline are associated with the formation of senile plaques, which are caused by the aggregation of β-amyloid (Aβ) peptides derived from amyloid precursor protein (APP). Additionally, AD patients exhibit reduced levels of acetylcholine, a neurotransmitter, due to the excessive production of acetylcholinesterase (AChE). In this study, we screened natural products for their inhibitory activities against Aβ secretion and AChE activity. The methanol extract of Dendrotrophe umbellata (Blume) Miq. (DUM) demonstrated inhibitory effects on both Aβ secretion and AChE activity. DUM reduced the secretion levels of Aβ42 and Aβ40 by 55% and 51%, respectively, at a concentration of 50 μg/mL. Furthermore, DUM exhibited a dose-dependent increase in sAPPα secretion and α-carboxy terminal fragment (CTF) levels at concentrations ranging from 10 μg/mL to 100 μg/mL. These results suggest that DUM inhibits β-secretase activity, thereby promoting the non-amyloidogenic pathway of APP metabolism at these concentrations. These findings reveal that DUM inhibits β-secretase, which competitively acts on APP, sharing the same substrate with α-secretase. Based on these results, we propose that DUM could serve as a natural resource to improve memory and cognition through β-secretase inhibition.