Involvement of bilitranslocase and beta-glucuronidase in the vascular protection by hydroxytyrosol and its glucuronide metabolites in oxidative stress conditions

Peyrol, Julien; Meyer, Grégory; Obert, Philippe; Dangles, Olivier; Pechère, Laurent; Amiot, Marie-Josèphe; Riva, Catherine

doi:10.1016/j.jnutbio.2017.09.009

Cited by 21 publications

(16 citation statements)

References 53 publications

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“…The pharmacokinetic analysis in rats indicated an extensive and fast uptake of these compounds by different organs including skeletal muscle, kidneys, liver, lungs, and heart [42]. A recent study by Peyrol et al [43] highlighted the importance of bilitranslocase in endothelial cell internalization of HT and its glucuronide metabolite. Moreover, it has been demonstrated that HT and its metabolites HT sulfate and HT acetate sulfate [40], as well as Tyr [44], are able to pass the blood brain barrier in rats and undergo brain uptake.…”

Section: Olive Oilmentioning

confidence: 99%

“…Indeed, several research groups pointed out that sulfate and glucuronide moieties can be deconjugated once they get intracellular environment, thus actually acting as free parent compounds and not as metabolites [50]. For example, Peyrol et al [43] showed that HT glucuronide exerted the same antioxidant activity of HT in endothelial cells: however, this was due to the intracellular β-glucuronidase action which favored deconjugation, leading to the formation of free HT. Moreover, Atzeri et al [60] observed that HT and Tyr sulfate, entered intestinal Caco-2 cells from 30 min of incubation and underwent an extensive metabolization, giving rise to a pool of metabolites, mainly sulfate and methyl-sulfate HT and Tyr.…”

Section: Activity Of Polyphenols Metabolitesmentioning

confidence: 99%

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Biological Relevance of Extra Virgin Olive Oil Polyphenols Metabolites

2018

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Extra virgin olive oil (EVOO) polyphenols beneficial effects have widely been debated throughout the last three decades, with greater attention to hydroxytyrosol and tyrosol, which are by far the most studied. The main concern about the evaluation of EVOO phenols activities in vitro and in vivo is that the absorption and metabolism of these compounds once ingested lead to the production of different metabolites in the human body. EVOO phenols in the ingested forms are less concentrated in human tissues than their glucuronide, sulfate and methyl metabolites; on the other hand, metabolites may undergo deconjugation before entering the cells and thus act as free forms or may be reformed inside the cells so acting as conjugated forms. In most in vitro studies the presence of methyl/sulfate/glucuronide functional groups does not seem to inhibit biological activity. Parent compounds and metabolites have been shown to reach tissue concentrations useful to exert beneficial effects others than antioxidant and scavenging properties, by modulating intracellular signaling and improving cellular response to oxidative stress and pro-inflammatory stimuli. This review aims to give an overview on the reported evidence of the positive effects exerted by the main EVOO polyphenols metabolites in comparison with the parent compounds.

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Section: Olive Oilmentioning

confidence: 99%

Section: Activity Of Polyphenols Metabolitesmentioning

confidence: 99%

Biological Relevance of Extra Virgin Olive Oil Polyphenols Metabolites

2018

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“…This protein is expressed in all cell types, with high expression in macrophages, and its activity is highest in the liver. β-glucuronidase activity increases in inflammation [176], and a low-grade inflammatory state is associated with ageing and age-related disease. It can be assumed that local concentrations of curcumin can differ from that detected in serum, as described for other polyphenols in tumor tissue [177].…”

Section: Curcuminmentioning

confidence: 99%

The Role of Curcumin in the Modulation of Ageing

Bielak-Żmijewska

Grabowska

Ciolko

et al. 2019

IJMS

108

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It is believed that postponing ageing is more effective and less expensive than the treatment of particular age-related diseases. Compounds which could delay symptoms of ageing, especially natural products present in a daily diet, are intensively studied. One of them is curcumin. It causes the elongation of the lifespan of model organisms, alleviates ageing symptoms and postpones the progression of age-related diseases in which cellular senescence is directly involved. It has been demonstrated that the elimination of senescent cells significantly improves the quality of life of mice. There is a continuous search for compounds, named senolytic drugs, that selectively eliminate senescent cells from organisms. In this paper, we endeavor to review the current knowledge about the anti-ageing role of curcumin and discuss its senolytic potential.

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“…Our results indicated that the activity of β-glucuronidase increased in senescent VSMCs (independently of the manner of senescence induction). The activity of β -glucuronidase increases during inflammation (Peyrol et al 2018). This enzyme can be released from granulocytes, including neutrophils (Marshall et al 1988).…”

Section: Discussionmentioning

confidence: 99%

Curcumin induces multiple signaling pathways leading to vascular smooth muscle cell senescence

et al. 2019

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Curcumin, a phytochemical present in the spice named turmeric, and one of the promising anti-aging factors, is itself able to induce cellular senescence. We have recently shown that cells building the vasculature senesced as a result of curcumin treatment. Curcumin-induced senescence was DNA damage-independent; however, activation of ATM was observed. Moreover, neither increased ROS production, nor even ATM were indispensable for senescence progression. In this paper we tried to elucidate the mechanism of curcumin-induced senescence. We analyzed the time-dependence of the level and activity of numerous proteins involved in senescence progression in vascular smooth muscle cells and how inhibition p38 or p38 together with ATM, two proteins involved in canonical signaling pathways, influenced cell senescence. We showed that curcumin was able to influence many signaling pathways of which probably none was dominant and sufficient to induce senescence by itself. However, we cannot exclude that the switch between initiation and progression of senescence is the result of the impact of curcumin on signaling pathways engaging AMPK, ATM, sirtuin 1 and p300 and on their reciprocal interplay. Cytostatic concentration of curcumin induced cellular stress, which exceeded the adaptive response and, in consequence, led to cellular senescence, which is triggered by time dependent activation of several signaling pathways playing diverse roles in different phases of senescence progression. We also showed that activity of β-glucuronidase, the enzyme involved in deconjugation of the main metabolites of curcumin, glucuronides, increased in senescent cells. It suggests a possible local elevation of curcumin concentration in the organism.Electronic supplementary materialThe online version of this article (10.1007/s10522-019-09825-2) contains supplementary material, which is available to authorized users.

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Involvement of bilitranslocase and beta-glucuronidase in the vascular protection by hydroxytyrosol and its glucuronide metabolites in oxidative stress conditions

Cited by 21 publications

References 53 publications

Biological Relevance of Extra Virgin Olive Oil Polyphenols Metabolites

Biological Relevance of Extra Virgin Olive Oil Polyphenols Metabolites

The Role of Curcumin in the Modulation of Ageing

Curcumin induces multiple signaling pathways leading to vascular smooth muscle cell senescence

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