24(S)-Saringosterol Prevents Cognitive Decline in a Mouse Model for Alzheimer’s Disease

Abstract

We recently found that dietary supplementation with the seaweed Sargassum fusiforme, containing the preferential LXRβ-agonist 24(S)-saringosterol, prevented memory decline and reduced amyloid-β (Aβ) deposition in an Alzheimer’s disease (AD) mouse model without inducing hepatic steatosis. Here, we examined the effects of 24(S)-saringosterol as a food additive on cognition and neuropathology in AD mice. Six-month-old male APPswePS1ΔE9 mice and wildtype C57BL/6J littermates received 24(S)-saringosterol (0.5 mg/25 g body weight/day) (APPswePS1ΔE9 n = 20; C57BL/6J n = 19) or vehicle (APPswePS1ΔE9 n = 17; C57BL/6J n = 19) for 10 weeks. Cognition was assessed using object recognition and object location tasks. Sterols were analyzed by gas chromatography/mass spectrometry, Aβ and inflammatory markers by immunohistochemistry, and gene expression by quantitative real-time PCR. Hepatic lipids were quantified after Oil-Red-O staining. Administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice without affecting the Aβ plaque load. Moreover, 24(S)-saringosterol prevented the increase in the inflammatory marker Iba1 in the cortex of APPswePS1ΔE9 mice (p < 0.001). Furthermore, 24(S)-saringosterol did not affect the expression of lipid metabolism-related LXR-response genes in the hippocampus nor the hepatic neutral lipid content. Thus, administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice independent of effects on Aβ load and without adverse effects on liver fat content. The anti-inflammatory effects of 24(S)-saringosterol may contribute to the prevention of cognitive decline.

Phytosterols: Potential Metabolic Modulators in Neurodegenerative Diseases

“…It also reduced the in vivo expression of ionized calcium-binding adapter molecule 1 (Iba1), a marker for microglial activation and inflammation. No effect was detected on the amount of Aβ plaques, hence suggesting the neuroinflammatory effects of 24(S)-saringosterol in the deterrence of cognitive decline or limited penetration through BBB [77].…”

Hizikia fusiformis: Pharmacological and Nutritional Properties

“…The total fucosterol concentrations in normal H. fusiformis extract (NH) and modified H. fusiformis extract (EH) were 0.249 and 1.067 mg/g, respectively [ 70 ]. Furthermore, fucosterol is an additional liver X receptor (LXR) agonist that may also play a role in the gene expression profile resulting from H. fusiforme supplementation [ 84 ]. Liver X receptors (LXRs), LXRα (NR1H3), and LXRβ (NR1H2) are nuclear receptors that control the metabolism of a variety of essential lipids, such as cholesterol and bile acids [ 85 ].…”

The Role of Dietary Lipids in Cognitive Health: Implications for Neurodegenerative Disease

“…Another sterol compound derived from seaweed with similar neuroprotective properties is saringosterol, derived from Sargassum fusiforme. In AD model mice, dietary supplementation with 24(S) saringosterol prevented memory decline and reduced Aβ deposition [ 156 ]. Thus, phytosterols also represent an important source of anti-inflammatory lipids that can be adopted as part of a dietary regimen to combat neuroinflammation.…”