Entry #: 43
Date: 25 March 2018
Section: Phenolic compounds
Topic: Hydroxytyrosol and derivative uptake in brain
Type: In vivo model
OliveNetTM Journal Club
Expert review of literature related to olives and olive oil
D. Elizabeth McCord, Nancy B. Ray and Tom C. Karagiannis
In vivo striatal measurement of hydroxytyrosol, and its metabolite (homovanillic alcokol), compared with its derivative nitrohydroxytyrosol
Gallardo et al
Citation / Year
(1) / 2014
Hydroxytyrosol, homovanillic alcohol, nitrohydroxytyrosol, brain penetration, brain microdialysis
Accumulating evidence indicates that adherence to the Mediterranean diet with a relatively high consumption of extra-virgin olive oil is associated with improved cognition and protection against neurodegenerative conditions (2, 3). While initial studies focussed on the beneficial effects of the major fatty acid component of olive oil (e.g. oleic acid), it is becoming apparent that the minor constituents, such as the potent anti-inflammatory and antioxidant, polyphenols are important for the beneficial health effects (4). In the context of cognition and neurodegenerative conditions, hydroxytyrosol is particularly important. Hydroxytyrosol is found in the brain as an endogenous catabolite of the catecholamine neurotransmitters dopamine and norepinephrine (5). Further, the 3-O-methylated derivative, homovanillic alcohol, produced by the activity of catechol-O-methyltransferase, is the major identifiable metabolite of hydroxytyrosol in humans (6, 7). Apart from understanding biological activity of hydroxytyrosol and derivatives, bioavailability and ability to cross the blood-brain-barrier are important aspects of investigation. In this study the phenolic compounds hydroxytyrosol, homovanillic alcohol, and the derivative nitro-hydroxytyrosol were measured in live rat brains by in vivo microdialysis coupled with high performance liquid chromatography and electrochemical detection.
Key points and implications
Firstly, although the methodology employed in this paper allowed for exquisite specificity at the femtogram level, basal endogenous levels of hydroxytyrosol were not detectable in rat striatum. The key findings indicated that administration of hydroxytyrosol (20 and 40 mg/kg intraperitoneal) resulted in a clear increase in the concentration of the compound in the rat striatum. The concentration peaked at approximately one hour and rapidly decreased to baseline at approximately two hours. The increase in concentration of hydroxytyrosol was accompanied an increase in the concentration of the major metabolite homovanillic alcohol. Similar findings – an increase in levels of homovanillic alcohol – was observed when 20 μM hydroxytyrosol was perfused through the microdialysis cannula. It is also noteworthy that saturation of catechol-O-methyltransferase activity was observed as conversion to homovanillic alcohol was not linear with administered dose of hydtroxytyrosol. The concentration of the hydroxytyrosol derivative, nitro-hydroxytyrosol also increased in rat striatum following intraperitoneal administration (20 and 40 mg/kg), however, it was one order of magnitude lower than concentrations reached with hydroxytyrosol. Given the biological activity of hydroxytyrosol and structurally related analogues, understanding the bioavailability including metabolic profiles and how they cross the blood-brain-barrier is of paramount importance. This study using a highly sensitive method to detect phenolic compounds has provided insights, indicating relatively high penetration of hydroxytyrosol into the brain striatum.
- E. Gallardo, R. Palma-Valdes, J. L. Espartero, M. Santiago, In vivo striatal measurement of hydroxytyrosol, and its metabolite (homovanillic alcohol), compared with its derivative nitrohydroxytyrosol. Neuroscience letters 579, 173-176 (2014).
- F. Sofi, R. Abbate, G. F. Gensini, A. Casini, Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis. The American journal of clinical nutrition 92, 1189-1196 (2010).
- I. Tasset, A. J. Pontes, A. J. Hinojosa, R. de la Torre, I. Tunez, Olive oil reduces oxidative damage in a 3-nitropropionic acid-induced Huntington’s disease-like rat model. Nutritional neuroscience 14, 106-111 (2011).
- F. Perez-Jimenez, J. Ruano, P. Perez-Martinez, F. Lopez-Segura, J. Lopez-Miranda, The influence of olive oil on human health: not a question of fat alone. Molecular nutrition & food research 51, 1199-1208 (2007).
- I. Lamensdorf et al., Metabolic stress in PC12 cells induces the formation of the endogenous dopaminergic neurotoxin, 3,4-dihydroxyphenylacetaldehyde. Journal of neuroscience research 60, 552-558 (2000).
- K. L. Tuck, P. J. Hayball, I. Stupans, Structural characterization of the metabolites of hydroxytyrosol, the principal phenolic component in olive oil, in rats. Journal of agricultural and food chemistry 50, 2404-2409 (2002).
- C. Manna et al., Transport mechanism and metabolism of olive oil hydroxytyrosol in Caco-2 cells. FEBS letters 470, 341-344 (2000).