Dietary Sargassum fusiforme improves memory and reduces amyloid plaque load in an Alzheimer’s disease mouse model

Abstract

Activation of liver X receptors (LXRs) by synthetic agonists was found to improve cognition in Alzheimer’s disease (AD) mice. However, these LXR agonists induce hypertriglyceridemia and hepatic steatosis, hampering their use in the clinic. We hypothesized that phytosterols as LXR agonists enhance cognition in AD without affecting plasma and hepatic triglycerides. Phytosterols previously reported to activate LXRs were tested in a luciferase-based LXR reporter assay. Using this assay, we found that phytosterols commonly present in a Western type diet in physiological concentrations do not activate LXRs. However, a lipid extract of the 24(S)-Saringosterol-containing seaweed Sargassum fusiforme did potently activate LXRβ. Dietary supplementation of crude Sargassum fusiforme or a Sargassum fusiforme-derived lipid extract to AD mice significantly improved short-term memory and reduced hippocampal Aβ plaque load by 81%. Notably, none of the side effects typically induced by full synthetic LXR agonists were observed. In contrast, administration of the synthetic LXRα activator, AZ876, did not improve cognition and resulted in the accumulation of lipid droplets in the liver. Administration of Sargassum fusiforme-derived 24(S)-Saringosterol to cultured neurons reduced the secretion of Aβ42. Moreover, conditioned medium from 24(S)-Saringosterol-treated astrocytes added to microglia increased phagocytosis of Aβ. Our data show that Sargassum fusiforme improves cognition and alleviates AD pathology. This may be explained at least partly by 24(S)-Saringosterol-mediated LXRβ activation.

Neuroprotective Effect of Methanolic Extract of Sargassum Wightii on Haloperidol Induced Catalepsy and Tardive Dyskinesia in Albino Rats

“…Studies on neuroprotective and antioxidant activities of Sargassum species have substantiated the role of various phytoconstituents. Presence of phenols, phytosterols, flavonoids, carotenoids, fucoxanthin, polysaccharides (fucoidan) and tannins in Sargassum (seaweeds) contribute to their promising antioxidant, antiinflammatory and neuroprotective properties [35][36][37]. The plant of our research interest, Sargassum wightii contains the same phytoconstituents.…”

Identification of the fructose transporter GLUT5 (SLC2A5) as a novel target of nuclear receptor LXR

“…For example, LXRα-selective antagonists or inverse agonists might be efficacious in the treatment of NAFLD without affecting reverse cholesterol transport 55 . On the other hand LXRβ-selective agonists are potentially useful to improve cognition in Alzheimer’s disease while avoiding stimulation of hepatic lipogenesis by LXRα, the predominant isoform in the liver 56 . GLUT5 expression is increased in the intestine and in skeletal muscle of T2D patients but also in certain cancers that are highly dependent on fructose uptake and metabolism, providing an alternative route for energy delivery during insulin resistance or to match increased energy demand caused by uncontrolled proliferation, respectively 28,29 .…”

Seaweeds: An Extensive Review of Medicinal Values

“…Several studies reported neuroprotective role of astaxanthin and fucoxanthin [145, [282][283][284][285][286][287], Sargassum spp. [288][289][290][291][292][293][294][295], Saccorhiza polyschide [283], Codium tomentosum [296], Ulva spp [256,267,293,[297][298][299][300], Ecklonia maxima [256,[301][302][303], Gracilaria spp. (Figure 12) [296,[304][305][306][307][308][309][310][311], Gelidium pristoides [312,313], Halimeda incrassate [314,315], Bryothamniom triquetrum [316][317][318], Chondrus crispus ( Figure 13) [319,320], Hypnea valentiae (…”