stigmasterol and Alzheimer-Disease

Our previous anti-Alzheimer's studies on crude extracts, essential oils and isolated compounds including β-sitostrol from

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid Precursor Protein Secretases; Animals; Aspartic Acid Endopeptidases; Ligands; Molecular Docking Simulation; Monoamine Oxidase; Parkinson Disease; Phytosterols; Polygonum; Stigmasterol

The number of patients diagnosed with Alzheimer's disease (AD) increases each year, and there are currently few treatment strategies to decrease the symptoms of AD; furthermore, these strategies are not sufficient to reduce memory loss in AD patients. In this work

Topics: Alzheimer Disease; Amyloid beta-Peptides; Humans; Peptide Fragments; Sargassum; Stigmasterol

In the current super-aging society, the establishment of methods for prevention and treatment of Alzheimer's disease (AD) is an urgent task. One of the causes of AD is thought to be a decrease in the revel of nerve growth factor (NGF) in the brain. Compounds showing NGF-mimicking activity and NGF-enhancing activity have been examined as possible agents for improving symptoms. In the present study, sunflower seed extract was found to have neurite outgrowth-promoting activity, which is an NGF-enhancing activity, in PC12 cells. To investigate neurite outgrowth-promoting compounds from sunflower seed extract, bioassay-guided purification was carried out. The purified active fraction was obtained by liquid-liquid partition followed by some column chromatographies. Proton nuclear magnetic resonance and gas chromatography-mass spectrometry analyses of the purified active fraction indicated that the fraction was a mixture of β-sitosterol, stigmasterol and campesterol, with β-sitosterol being the main component. Neurite outgrowth-promoting activities of β-sitosterol, stigmasterol, campesterol and cholesterol were evaluated in PC12 cells. β-Sitosterol and stigmasterol showed the strongest activity of the four sterol compounds (β-sitosterol ≈ stigmasterol > campesterol > cholesterol), and cholesterol did not show any activity. The results indicated that β-sitosterol was the major component responsible for the neurite outgrowth-promoting activity of sunflower seeds. Results of immunostaining also showed that promotion by β-sitosterol of neurite formation induced by NGF was accompanied by neurofilament expression. β-Sitosterol, which showed NGF-enhancing activity, might be a candidate ingredient in food for prevention of AD.

Topics: Alzheimer Disease; Animals; Brain; Cholesterol; Gene Expression Regulation; Helianthus; Humans; Nerve Growth Factor; Neurites; Neuronal Outgrowth; PC12 Cells; Phytosterols; Plant Extracts; Rats; Seeds; Sitosterols; Stigmasterol

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 Aβ

Topics: Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Animals; Astrocytes; Cognition; Culture Media, Conditioned; Disease Models, Animal; Gene Expression Regulation; Genes, Reporter; Hippocampus; Humans; Liver X Receptors; Luciferases; Male; Memory, Short-Term; Mice; Mice, Transgenic; Microglia; Neuroprotective Agents; Peptide Fragments; Plaque, Amyloid; Sargassum; Signal Transduction; Stigmasterol; Thiazoles

Amyloid-β (Aβ), major constituent of senile plaques in Alzheimer's disease (AD), is generated by proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretase. Several lipids, especially cholesterol, are associated with AD. Phytosterols are naturally occurring cholesterol plant equivalents, recently been shown to cross the blood-brain-barrier accumulating in brain. Here, we investigated the effect of the most nutritional prevalent phytosterols and cholesterol on APP processing. In general, phytosterols are less amyloidogenic than cholesterol. However, only one phytosterol, stigmasterol, reduced Aβ generation by (1) directly decreasing β-secretase activity, (2) reducing expression of all γ-secretase components, (3) reducing cholesterol and presenilin distribution in lipid rafts implicated in amyloidogenic APP cleavage, and by (4) decreasing BACE1 internalization to endosomal compartments, involved in APP β-secretase cleavage. Mice fed with stigmasterol-enriched diets confirmed protective effects in vivo, suggesting that dietary intake of phytosterol blends mainly containing stigmasterol might be beneficial in preventing AD.

Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Blotting, Western; Brain Chemistry; Cell Line, Tumor; Cholesterol; Enzyme-Linked Immunosorbent Assay; Flame Ionization; Gas Chromatography-Mass Spectrometry; Humans; Male; Membrane Microdomains; Mice; Mice, Inbred C57BL; Phytosterols; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Stigmasterol

The Herb Rhinacanthus nasutus (L.) Kurz, which is native to Thailand and Southeast Asia, has become known for its antioxidant properties. Neuronal loss in a number of diseases including Alzheimer's disease is thought to result, in part, from oxidative stress. Glutamate causes cell death in the mouse hippocampal cell line, HT-22, by unbalancing redox homeostasis, brought about by a reduction in glutathione levels, and amyloid-β has been shown to induce reactive oxygen species (ROS) production. Here in, we show that ethanol extracts of R. nasutus leaf and root are capable of dose dependently attenuating the neuron cell death caused by both glutamate and amyloid-β treatment. We used free radical scavenging assays to measure the extracts antioxidant activities and as well as quantifying phenolic, flavonoid and sterol content. Molecules found in R. nasutus, lupeol, stigmasterol and β-sitosterol are protective against glutamate toxicity.

Topics: Acanthaceae; Alzheimer Disease; Amyloid beta-Peptides; Animals; Antioxidants; Cell Line; Glutamic Acid; Glutathione; Hippocampus; Mice; Neuroprotective Agents; Neurotoxicity Syndromes; Oxidative Stress; Pentacyclic Triterpenes; Plant Extracts; Plant Leaves; Plant Roots; Reactive Oxygen Species; Sitosterols; Stigmasterol