3,4-Dihydroxyphenylglycol

A study of the precursors of the natural antioxidant phenol 3,4-dihydroxyphenylglycol in olive oil waste.[Pubmed:23578627]

Food Chem. 2013 Sep 1;140(1-2):154-60.

3,4-Dihydroxyphenylglycol (DHPG) is a potent antioxidant recently found in the free form in olive oil and table olives. DHPG can be recovered from olive oil solid waste by a hydrothermal treatment. It was observed that an increase in the concentration of DHPG occurred when alperujo aqueous extracts were subjected to mild thermal conditions (post-treatment). This fact indicates that certain solubilized compounds or precursors containing DHPG which is released with the post-treatment. In the present study, the precursors of DHPG were identified and characterized after extraction from alperujo using thermal treatment and purification by fractionation on Amberlite(R) XAD16 polyamide and semi-preparative reverse-phase HPLC columns. Their structures were elucidated using HPLC coupled to diode array detector (DAD) and electrospray ionization mass spectrometry (ESI-MS). The results identified three compounds as precursors, and their structures can be attributed to the diastereoisomeric forms of the two beta-hydroxy derivatives of verbascoside and isoverbascoside (beta-hydroxyacteoside and beta-hydroxyisoacteoside), and 2''-hydroxyoleuropein, all of which contain a DHPG moiety, potentially explaining the increases in the concentration of this phenolic compound in olive oil waste.

Pharmacodynamics of norepinephrine reuptake inhibition: Modeling the peripheral and central effects of atomoxetine, duloxetine, and edivoxetine on the biomarker 3,4-dihydroxyphenylglycol in humans.[Pubmed:26011686]

J Clin Pharmacol. 2015 Dec;55(12):1422-31.

Norepinephrine, a neurotransmitter in the autonomic sympathetic nervous system, is deaminated by monoamine oxidase to 3,4-Dihydroxyphenylglycol (DHPG). Inhibition of the NE transporter (NET) using DHPG as a biomarker was evaluated using atomoxetine, duloxetine, and edivoxetine as probe NET inhibitors. Pharmacokinetic and pharmacodynamic data were obtained from healthy subjects (n = 160) from 5 clinical trials. An indirect response model was used to describe the relationship between drug plasma concentration and DHPG concentration in plasma and cerebrospinal fluid (CSF). The baseline plasma DHPG concentration (1130-1240 ng/mL) and Imax (33%-37%) were similar for the 3 drugs. The unbound plasma drug IC50 (IC50U ) based on plasma DHPG was 0.973 nM for duloxetine, 0.136 nM for atomoxetine, and 0.041 nM for edivoxetine. The baseline CSF DHPG concentration (1850-2260 ng/mL) was similar for the 3 drugs, but unlike plasma DHPG, the Imax for DHPG was 38% for duloxetine, 53% for atomoxetine, and75% for edivoxetine. The IC50U based on CSF DHPG was 2.72 nM for atomoxetine, 1.22 nM for duloxetine, and 0.794 nM for edivoxetine. These modeling results provide insights into the pharmacology of NET inhibitors and the use of DHPG as a biomarker.

Naturally occurring hydroxytyrosol derivatives: hydroxytyrosyl acetate and 3,4-dihydroxyphenylglycol modulate inflammatory response in murine peritoneal macrophages. Potential utility as new dietary supplements.[Pubmed:25526103]

J Agric Food Chem. 2015 Jan 28;63(3):836-46.

This work evaluated the effects of extra virgin olive oil (EVOO) phenols, hydroxytyrosyl acetate (2) and 3,4-Dihydroxyphenylglycol (3), as well as two new acyl derivatives of 3, 4-(1,2-di(butanoyloxy)ethyl)benzene-1,2-diol (7) and 4-(1,2-di(lauroyloxy)ethyl)benzene-1,2-diol (8), on LPS-stimulated murine peritoneal macrophages in comparison with hydroxytyrosol (HTy, 1). Compounds 2, 3, 7, and 8 showed a strong reactive oxygen species (ROS)-scavenging activity, reducing significantly nitrite levels with a significant decrease on iNOS expression [2 (50 muM, 0.44 +/- 0.03; 100 muM, 0.44 +/- 0.01; p < 0.01); 3 (50 muM, 0.37 +/- 0.03; 100 muM, 0.37 +/- 0.01; p < 0.001); 7 (50 muM, 0.45 +/- 0.06; p < 0.01)] . However, only 2 and 3 down-regulated COX-2 expression [2 (50 muM, 0.72 +/- 0.04, p < 0.05; 100 muM, 0.54 +/- 0.06, p < 0.01); 3 (50 muM, 0.56 +/- 0.05, p < 0.05; 100 muM, 0.37 +/- 0.04; p < 0.001)] and prevented IKBalpha degradation [2 (100 muM, 1.63 +/- 0.14, p < 0.01); 3 (100 muM, 1.82 +/- 0.09; p < 0.01)] ; the diacylated compounds 7 and 8 showed worse anti-inflammatory activity than the parent 3. In conclusion, 2 and 3 phenolic derivatives could play an important role in the anti-inflammatory effect of EVOO. The implication of this study for the nutrition and general health of the population rests in the possible use of natural HTy derivatives with better hydrophilic/lipophilic balance, thus improving its pharmacodynamic and pharmacokinetic profiles, as new dietary supplements in foods.

Plasma 3,4-dihydroxyphenylglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are insensitive indicators of alpha 2-adrenoceptor mediated regulation of norepinephrine release in healthy human volunteers.[Pubmed:1646924]

Life Sci. 1991;49(1):75-84.

The usefulness of the plasma concentrations of two major metabolites of norepinephrine (NE), 3,4-Dihydroxyphenylglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG), as indicators of neuronal NE release was investigated. The potent alpha 2-adrenoceptor agonist, dexmedetomidine, induced only about 15% maximal reductions in the metabolite concentrations, in spite of almost total inhibition of neuronal NE release, as evidenced by 90% reductions in plasma NE concentrations. Similarly, administration of the alpha 2-adrenoceptor antagonist atipamezole was followed by only small increases in plasma DHPG and no change in MHPG levels, in spite of almost six-fold, albeit short-lasting, increases in plasma NE. In contrast, a single dose of the reversible monoamine oxidase type A (MAO-A) inhibitor moclobemide reduced plasma DHPG levels by 78% and MHPG levels by 51%. It is concluded that the plasma concentrations of DHPG and MHPG are largely determined by intraneuronal, MAO-A-dependent metabolism of NE, and do not accurately reflect acute alterations in neuronal NE release. The concentration of NE in venous plasma is clearly a more sensitive indicator of alpha 2-adrenoceptor-mediated regulation of NE release.

Alperujo extract, hydroxytyrosol, and 3,4-dihydroxyphenylglycol are bioavailable and have antioxidant properties in vitamin E-deficient rats--a proteomics and network analysis approach.[Pubmed:22648667]

Mol Nutr Food Res. 2012 Jul;56(7):1137-47.

SCOPE: Olive products are rich in phenolic compounds, which are natural antioxidants in vitro. We tested the in vivo effects of alperujo, an olive production by-product, as well as hydroxytyrosol and 3,4-Dihydroxyphenylglycol (DHPG) isolated from alperujo, on indices and pathways of oxidative and metabolic stress in a vitamin E-deficient rat model. METHODS AND RESULTS: Rats were fed a vitamin E-deficient diet for 10 weeks, followed by this diet supplemented with either 100 mg/kg diet dalpha-tocopherol, alperujo extract, hydroxytyrosol, or 10 mg/kg diet DHPG, for a further 2 weeks. We detected alperujo phenolics in tissues and blood, indicating they are bioavailable. Alperujo extract partially ameliorated elevated plasma levels of thiobarbituric acid reactive substances and also lowered plasma cholesterol levels, whereas hydroxytyrosol increased plasma triglyceride levels. Proteomics and subsequent network analysis revealed that hepatic mitochondrial aldehyde dehydrogenase (ALDH2), of which protein and activity levels were regulated by dalpha-tocopherol and olive phenolics, represents a novel central regulatory protein hub affected by the dietary interventions. CONCLUSION: The in vivo free radical scavenging properties of olive phenolics appear relatively modest in our model. But alternative mechanisms, including regulation of ALDH2, may represent relevant antioxidant mechanisms by which dietary olive phenolics could have beneficial impact on cardiovascular health.