Hydroxytyrosol Acetate Improves the Cognitive Function of APP/PS1 Transgenic Mice in ERβ‐dependent Manner

Abstract

ScopeAlzheimer's disease (AD) is the most prevalent form of dementia in the aging population; however, no effective therapy has been established. It has been previously demonstrated that daily intake of hydroxytyrosol (HT), a polyphenol in olive oil, at a daily dietary level mildly improves cognition in AD mice. In the present study, HT acetate (HT‐ac), which is a natural derivative of HT in olive oil that exhibits better bioactivity than HT improves cognition.Methods and ResultsHT‐ac to APP/PS1 is orally administered to transgenic mice and used Aβ‐treated neuronal cultures to explore the neuroprotective effects of HT‐ac in preventing AD progression. It is found that HT‐ac remarkably improved the escape latency, escape distance, and the number of platform crossings of AD mice in the water maze test by ameliorating neuronal apoptosis and decreasing inflammatory cytokine levels. It is further demonstrated that HT‐ac stimulated the transcription of ERβ and enhanced neuronal viability and electrophysiological activity in primary neurons but that these beneficial effects of HT‐ac are abolished upon ERβ deficiency.ConclusionsThis study suggests that as the bioactive component of olive oil, HT‐ac is a promising neuroprotective nutrient that may be used to alleviate AD‐related cognitive dysfunction.

Recovery of Hydroxytyrosol from Olive Mill Wastewater Using the Promiscuous Hydrolase/Acyltransferase PestE

“…[36][37][38] HTA-enriched functional foods could have neuroprotective, anticoagulant, arthritis preventive and other health-promoting properties. [4,8,39,40] For example, olive oil that contains 250 mg kg À 1 hydroxytyrosol derivatives can be called healthpromoting according to an EU regulation (EU Commission Regulation No. 432/2012).…”

“…The phenols of olives have several healthpromoting properties, e. g., neuroprotective, which are associated with their antioxidant and anti-inflammatory benefits. [4][5][6][7][8] Several methods have been developed to facilitate the degradation or extraction of phenolic compounds, such as chemical oxidation, solvent extraction, membrane systems or adsorbents. [9][10][11][12][13][14][15][16][17][18][19][20] However, all these systems require several laborious steps.…”

“…[11] Lipophilization of HT by acetylation could facilitate the extraction and increase the bioavailability of the extracted health-promoting 3-hydroxytyrosol acetate (HTA). [4,21] However, acetylation/transesterification in an aqueous medium is challenging, as the hydrolysis of the formed ester and acyl donor is thermodynamically favored and thus pure organic solvents must be used for lipase-catalyzed acetylation. [22] As an alternative, promiscuous acyltransferases are able to catalyze the acetylation of nucleophiles with an acyl donor in a kinetically controlled manner in an aqueous system, thus favoring acetylation over hydrolysis.…”

Protection against Amyloid-β Oligomer Neurotoxicity by Small Molecules with Antioxidative Properties: Potential for the Prevention of Alzheimer’s Disease Dementia

“…Notably, AβOi-induced abnormalities in PI3K/Akt1, ERK/MAPK/RSK2, JAK2/STAT3, and JNK/p38 signaling pathways were reversed by HT. A recent study also reported that oral administration of HT acetate (50 mg/kg) into APP/PS1 mice for 3 months (from 3.5 to 6.5 months old) attenuated apoptosis in the cortex and hippocampus and improved cognitive function, measured using T-maze and MWM tests [ 29 ].…”

Tailored Functionalization of Natural Phenols to Improve Biological Activity

“…The promising pharmacological activities of hydroxytyrosol (as cardioprotective, anticancer, neuroprotective and antimicrobial agent) have been recently reviewed [ 79 , 244 ]. Analogously, hydroxytyrosol acetate (2-(3,4-dihydroxyphenyl)ethylacetate), a diphenolic constituent of olive oil, is characterized by peculiar biological activities [ 245 , 246 , 247 , 248 ]. Several hydroxytyrosol derivatives have been explored over the past decades, to extend its biological applications [ 249 , 250 , 251 , 252 ].…”