Abstract
According to the cholinergic hypothesis, memory impairment in patients with Alzheimer’s disease (AD) is associated with the deficit of cholinergic function in the brain. In addition, microglial activation plays an important role in AD by producing pro-inflammatory cytokines, nitric oxide (NO), and prostaglandin E2 (PGE2). It was noted that lipopolysaccharide (LPS) and β-amyloid (Aβ) induced microglial activation leading to neuroinflammation and ultimately neuronal cell death. Fucosterol, a plant sterol found in brown algae, has been reported to exhibit several bioactivities. This study aimed to investigate the anti-cholinesterase activities of fucosterol and its effects on the release of pro-inflammatory mediators by LPS- and Aβ-induced microglial cells. Cholinesterase inhibition was determined using the modified Ellman colorimetric method. Expression of pro-inflammatory mediators was determined using RT-PCR and ELISA. The NO content was determined using the Griess test. Fucosterol exhibited dose-dependent inhibitory activities against both acetylcholinesterase and butyrylcholinesterase. It significantly inhibited the production of cytokines, namely interleukins (IL-6, IL-1β), tumor necrosis factor-α (TNF-α), NO, and PGE2 in LPS- or Aβ-induced microglial cells. Fucosterol provided protective effects against Aβ-mediated neuroinflammation by inhibiting the production of pro-inflammatory mediators. These findings provided insights into the development of fucosterol as a potential drug candidate for AD, a multifactorial neurodegenerative disorder.
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We gratefully acknowledge the Ministry of Science, Technology and Innovation, Malaysia (E-Science Project no. 02-02-09-SF0017), the Ministry of Higher Education (FRGS/1/2013/ST03/IMU/02/1), and IMU Pharmacy Research Project (BP I-01/13(04)2016) for funding the research work.
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Wong, C.H., Gan, S.Y., Tan, S.C. et al. Fucosterol inhibits the cholinesterase activities and reduces the release of pro-inflammatory mediators in lipopolysaccharide and amyloid-induced microglial cells. J Appl Phycol 30, 3261–3270 (2018). https://doi.org/10.1007/s10811-018-1495-1
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DOI: https://doi.org/10.1007/s10811-018-1495-1