Hydroxytyrosol: from laboratory investigations to future clinical trials

Granados-Principal, Sergio; Quiles, José L.; Ramírez-Tortosa, César L.; Sánchez‐Rovira, Pedro; Ramírez-Tortosa, M. C.

doi:10.1111/j.1753-4887.2010.00278.x

Cited by 269 publications

(208 citation statements)

References 141 publications

(324 reference statements)

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“…It is necessary to bear in mind that hydroxytyrosol is a product derived from hydrolysis of oleuropein (Granados-Principal, Quiles, Ramirez-Tortosa, Sanchez-Rovira, & Ramirez-Tortosa, 2010). For this reason, both oleuropein and hydroxytyrosol exhibit similar evolution during the ripening process and similar response to ABA.…”

Section: Resultsmentioning

confidence: 99%

Abscisic Acid Sprayed on Olive Tree (Olea europaea L.) Affects the Phenolic Composition of Olive Fruit Cultivars

Blanch¹,

Flores²,

Gómez-Jiménez³

et al. 2018

JAS

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The aim of this research was to study the effect of abscisic acid pre-harvest treatment on the phenolic composition of olive fruits. To that end we applied abscisic acid (i.e., 50 mg/L and 100 mg/L) on Arbequina and Picual olive trees. Two different days of harvesting (i.e., day 3 and 6 after treatment) were also included in the study. Although the results obtained depended on the cultivar and on the day of harvesting a general trend was established. The treatment with 50 mg/L of abscisic acid resulted in higher total phenol content but significant decrease in the DPPH activity. In contrast, olives treated with 100 mg/L abscisic acid resulted in higher total phenol content, DPPH activity and contents of oleuropein, hydroxytyrosol and phenolic acids as compared with controls. The best values of total phenol content and IC 50 were obtained for treated Picual olives (727.75 mg gallic kg -1 and 889.72 µg/ml, respectively) whereas the highest values of oleuropein and hydroxytyrosol were measured for treated Arbequina olives (508.94 and 559.67 mg kg -1 , respectively). Phenolic acid content was also higher in Picual olives treated with 100 mg/L of abscisic acid. Particulary, values ranged from 7.26 mg kg -1 for caffeic acid to 92.38 mg kg -1 for chlorogenic acid. Exogenous abscisic acid applied to olive trees is a promising agronomic practice to obtain olives enriched in antioxidants.

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Section: Resultsmentioning

confidence: 99%

Abscisic Acid Sprayed on Olive Tree (Olea europaea L.) Affects the Phenolic Composition of Olive Fruit Cultivars

Blanch¹,

Flores²,

Gómez-Jiménez³

et al. 2018

JAS

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“…To determine whether ROS were involved in POM1 neurotoxicity in vivo, we administered the enterically activated antioxidant, acetylated hydroxytyrosol 21 (AcHyt) to tga20 mice. Five of six untreated, but only one of six AcHyt-treated, tga20 mice developed cerebellar lesions upon scFv POM1 injection ( Fig.…”

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confidence: 99%

The toxicity of antiprion antibodies is mediated by the flexible tail of the prion protein

Sonati

Reimann

Falsig

et al. 2013

Nature

196

289

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Prion infections cause lethal neurodegeneration. This process requires the cellular prion protein (PrP(C); ref. 1), which contains a globular domain hinged to a long amino-proximal flexible tail. Here we describe rapid neurotoxicity in mice and cerebellar organotypic cultured slices exposed to ligands targeting the 1 and 3 helices of the PrP(C) globular domain. Ligands included seven distinct monoclonal antibodies, monovalent Fab1 fragments and recombinant single-chain variable fragment miniantibodies. Similar to prion infections, the toxicity of globular domain ligands required neuronal PrP(C), was exacerbated by PrP(C) overexpression, was associated with calpain activation and was antagonized by calpain inhibitors. Neurodegeneration was accompanied by a burst of reactive oxygen species, and was suppressed by antioxidants. Furthermore, genetic ablation of the superoxide-producing enzyme NOX2 (also known as CYBB) protected mice from globular domain ligand toxicity. We also found that neurotoxicity was prevented by deletions of the octapeptide repeats within the flexible tail. These deletions did not appreciably compromise globular domain antibody binding, suggesting that the flexible tail is required to transmit toxic signals that originate from the globular domain and trigger oxidative stress and calpain activation. Supporting this view, various octapeptide ligands were not only innocuous to both cerebellar organotypic cultured slices and mice, but also prevented the toxicity of globular domain ligands while not interfering with their binding. We conclude that PrP(C) consists of two functionally distinct modules, with the globular domain and the flexible tail exerting regulatory and executive functions, respectively. Octapeptide ligands also prolonged the life of mice expressing the toxic PrP(C) mutant, PrP(Δ94-134), indicating that the flexible tail mediates toxicity in two distinct PrP(C)-related conditions. Flexible tail-mediated toxicity may conceivably play a role in further prion pathologies, such as familial Creutzfeldt-Jakob disease in humans bearing supernumerary octapeptides. (Fig. 1b). None of three high-affinity antibodies to the octapeptide repeats (OR, residues 50-90 embedded within the FT) were neurotoxic (Fig. 1b). Antibodies POM3 and D13, which bind the "charged cluster-2" 11 (CC2, residues 95-110), were innocuous at 67 nM but neurotoxic at 200 nM (Fig. 1b). None of the tested antibodies were toxic to Prnp o/o COCS ( Supplementary Fig. 2a). The identity of the targeted epitopes appeared to be a better predictor of PrP C antibody toxicity than their affinity to PrP C , suggesting that neurotoxicity resulted from the interaction of antibodies with specific PrP C domains (Supplementary Table 2).The mechanisms of neurotoxicity were further explored using POM1, a highly toxic antibody targeting the GD. Wild-type (wt) and tga20 COCS lost most granule cells (CGC) within 28 and 14 days post-exposure (dpe) to POM1, respectively (Fig. 2a-c). Controls included POM1-treated Prnp o/o COCS 12 , t...

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“…The effects of LACHI MIX HT were examined on oxidative stress levels, chloride and potassium channel conductances and excitability of the sarcolemma, calcium homeostasis and contractile function, muscle atrophy, and muscle force, all of which are sensitive to the activity of ROS. The effects of LACHI MIX HT were compared with those of purified HT, already proposed in different therapies, i.e., anticancer or cardioprotective (Granados-Principal et al 2010;Warleta et al 2011;Castañer et al 2012). …”

Section: Introductionmentioning

confidence: 99%

An olive oil-derived antioxidant mixture ameliorates the age-related decline of skeletal muscle function

Pierno

Tricarico

Liantonio

et al. 2013

AGE

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Age-related skeletal muscle decline is characterized by the modification of sarcolemma ion channels important to sustain fiber excitability and to prevent metabolic dysfunction. Also, calcium homeostasis and contractile function are impaired. In the aim to understand whether these modifications are related to oxidative damage and can be reverted by antioxidant treatment, we examined the effects of in vivo treatment with an waste water polyphenolic mixture (LACHI MIX HT) supplied by LACHIFARMA S.r.l. Italy containing hydroxytirosol (HT), gallic acid, and homovanillic acid on the skeletal muscles of 27-month-old rats. After 6-week treatment, we found an improvement of chloride ClC-1 channel conductance, pivotal for membrane electrical stability, and of ATP-dependent potassium channel activity, important in coupling excitability with fiber metabolism. Both of them were analyzed using electrophysiological techniques. The treatment also restored the resting cytosolic calcium concentration, the sarcoplasmic reticulum calcium release, and the mechanical threshold for contraction, an index of excitation-contraction coupling mechanism. Muscle weight and blood creatine kinase levels were preserved in LACHI MIX HT-treated aged rats. The antioxidant activity of LACHI MIX HT was confirmed by the reduction of malondialdehyde levels in the brain of the LACHI MIX HT-treated aged rats. In comparison, the administration of purified HT was less effective on all the parameters studied. Although muscle function was not completely recovered, the present study provides evidence of the beneficial effects of LACHI MIX HT, a natural compound, to ameliorate skeletal muscle functional decline due to aging-associated oxidative stress.

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Hydroxytyrosol: from laboratory investigations to future clinical trials

Cited by 269 publications

References 141 publications

Abscisic Acid Sprayed on Olive Tree (Olea europaea L.) Affects the Phenolic Composition of Olive Fruit Cultivars

Abscisic Acid Sprayed on Olive Tree (Olea europaea L.) Affects the Phenolic Composition of Olive Fruit Cultivars

The toxicity of antiprion antibodies is mediated by the flexible tail of the prion protein

An olive oil-derived antioxidant mixture ameliorates the age-related decline of skeletal muscle function

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