Abstract
Alzheimer’s disease (AD) is a progressive, neurodegenerative brain disorder associated with loss of memory and cognitive function. Beta-amyloid (Aβ) aggregates, in particular, are known to be highly neurotoxic and lead to neurodegeneration. Therefore, blockade or reduction of Aβ aggregation is a promising therapeutic approach in AD. We have previously reported an inhibitory effect of the methanol extract of Perilla frutescens (L.) Britton (Lamiaceae) and its hexane fraction on Aβ aggregation. Here, the hexane fraction of P. frutescens was subjected to diverse column chromatography based on activity-guided isolation methodology. This approach identified five asarone derivatives including 2,3-dimethoxy-5-(1E)-1-propen-1-yl-phenol (1), β-asarone (2), 3-(2,4,5-trimethoxyphenyl)-(2E)-2-propen-1-ol (3), asaronealdehyde (4), and α-asarone (5). All five asarone derivatives efficiently reduced the aggregation of Aβ and disaggregated preformed Aβ aggregates in a dose-dependent manner as determined by a Thioflavin T (ThT) fluorescence assay. Furthermore, asarone derivatives protected PC12 cells from Aβ aggregate-induced toxicity by reducing the aggregation of Aβ, and significantly reduced NO production from LPS-stimulated BV2 microglial cells. Taken together, these results suggest that asarone derivatives derived from P. frutescens are neuroprotective and have the prophylactic and therapeutic potential in AD.
Highlights
Alzheimer’s disease (AD) is a chronic, progressive neurodegenerative brain disorder associated with declining memory and cognitive function, occurring in middle or late life [1]
In order to isolate the active constituents of these extracts responsible for inhibiting amyloid β-peptide (Aβ) aggregation, the hexane fraction of P. frutescens was subjected to diverse column chromatographic separation using silica-gel, Sephadex LH-20, and C18 as stationary phases to isolate the active compounds based on the bioassay-guided isolation method
Senile plaques composed of Aβ peptides, one of the pathologic hallmarks of AD, are generated by proteolytic fragmentation of amyloid precursor protein (APP)
Summary
Alzheimer’s disease (AD) is a chronic, progressive neurodegenerative brain disorder associated with declining memory and cognitive function, occurring in middle or late life [1]. The etiology of AD is poorly understood, many experts suggest that the disease results from a complex interplay of multiple factors rather than any one overriding cause. The predominant “amyloid cascade” hypothesis for AD development proposes that extracellular amyloid β-peptide (Aβ) deposits are fundamental to the pathology of AD [2]. Molecules 2019, 24, 4297 and γ-secretase to form the Aβ peptide. Aβ peptides can stimulate glial cells to produce cytotoxic molecules such as nitric oxide (NO), reactive oxygen species (ROS), and other pro-inflammatory cytokines which significantly contribute to neuronal damage and death [5,6]. Blockade or reduction of Aβ aggregation is a promising therapeutic approach
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
