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Effects and Possible Mechanisms of Action of Acacetin on The Behavior and Eye Morphology of Drosophila Models of Alzheimer’s Disease
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- URLhttps://db.koreascholar.com/Article/Detail/313073
The human β-amyloid (Aβ) cleaving enzyme (BACE-1) is a target for Alzheimer’s disease (AD) treatments. This study was conducted to determine if acacetin extracted from the whole Agastache rugosa plants had anti-BACE-1 and behavioral activities in Drosophila AD models and to determine acacetin’s mechanism of action. Acacetin (100, 300, and 500 μM) rescued amyloid precursor protein (APP)/BACE1-expressing flies and kept them from developing both eye morphology (dark deposits, ommatidial collapse and fusion, and the absence of ommatidial bristles) and behavioral (motor abnormalities) defects. The RT-PCR and Western blot analysis revealed that the protective effect of acacetin on Aβ production is mediated by transcriptional regulation of BACE-1 and APP, resulting in decreased APP protein expression and BACE-1 activity, and reduced Aβ production by interfering with BACE-1 activity and APP synthesis, resulting in a decrease in the levels of the APP carboxy terminal fragments and the APP intracellular domain, and finally, resulting in a decrease in the number of amyloid plaques.
