β-sitosterol inhibits high cholesterol-induced platelet β-amyloid release

Abstract

Recently, increasing evidence has linked high cholesterol to the pathogenesis of Alzheimer's disease (AD), suggesting that cholesterol may be a target for developing new compounds to prevent or treat AD. Plant sterols, a group of sterols enriched in plant oils, nuts, and avocados, have the structure very similar to that of cholesterol, and have been widely used to reduce blood cholesterol. Due to their cholesterol-lowering property, plant sterols such as β-sitosterol may also influence cholesterol-depending functions including its role in AD development. Using human platelets, a type of peripheral blood cells containing the most circulating amyloid precursor protein (APP), this study investigated the effect of β-sitosterol on high cholesterol-induced secretion of β amyloid protein (Aβ). It was found that β-sitosterol effectively inhibited high cholesterol-driven platelet Aβ release. In addition, β-sitosterol prevented high cholesterol-induced increase of activities of β- and γ-secretase, two APP cleaving enzymes to generate Aβ. Additional experiments showed that high cholesterol up-regulated lipid raft cholesterol. This effect of cholesterol could be suppressed by β-sitosterol. These findings suggest that β-sitosterol is able to inhibit high cholesterol-induced Aβ release probably through maintenance of membrane cholesterol homeostasis. Given that dietary plant sterols have the potential of penetrating the blood-brain barrier (BBB), these data suggest that plant sterols such as β-sitosterol may be useful in AD prevention.

Systems Pharmacology-based strategy to screen new adjuvant for hepatitis B vaccine from Traditional Chinese Medicine Ophiocordyceps sinensis

“…Sito is a functional phytosterol with a chemical structure similar to that of cholesterol55. Sito alone or combined with other plant sterols is known to reduce blood cholesterol levels by blocking cholesterol absorption5657. Sito has also been reported to possess antimicrobial activity58.…”

Plant sterols: Friend or foe in CNS disorders?

“…3a and c) [166]. Moreover, in a platelet-model for Ab production, sitosterol inhibits high cholesterol-induced Ab release, likely through maintenance of membrane cholesterol homeostasis [139]. Similarly, it was found that stigmasterol significantly reduces cholesterol and presenilin distribution in lipid rafts.…”

“…Phytosterols have been shown to beneficially modulate molecular processes involved in AD, such as APP processing and amyloid beta plaque formation in several in vitro and in vivo experimental setups [137][138][139]. In the next paragraphs, we discuss three theoretical models on how plant sterols may modulate AD on the molecular level.…”

Incorporation of β-sitosterol into the membrane prevents tumor necrosis factor-α-induced nuclear factor-κB activation and gonadotropin-releasing hormone decline

“…Plasma membranes were isolated by sucrose density gradient centrifugation as in our previous studies [8][9][10]. Quantitative analysis of BS and cholesterol was performed as in our previous studies [10][11].…”