Elsevier

Food Research International

Volume 92, February 2017, Pages 56-63
Food Research International

Evaluation of an olive leaf extract as a natural source of antiglycative compounds

https://doi.org/10.1016/j.foodres.2016.12.017Get rights and content

Highlights

  • An olive leaf extract obtained by acid extraction was characterized.

  • The antiglycative activity of the extract is mainly exerted at the advanced stage.

  • Carboxymethyllysine was more efficiently inhibited than argpyrimidine.

  • The main mechanism of action is mediated by direct trapping of dicarbonyl compounds.

Abstract

Advanced Glycation End-products (AGEs) have been associated to diabetes, neurodegenerative and cardiovascular diseases. Mitigating the formation of AGEs is a strategy to avoid detrimental physiopathological effects of age-related chronic diseases. An olive leaf extract (OLE), obtained under acidic conditions, and two fractions, obtained by solid-phase extraction, were characterized by LC–MS/MS. Antiglycative capacity of OLE and fractions were investigated in different in vitro models. The OLE significantly inhibited the formation of Amadori products at the early stage as well as the formation of fluorescent AGEs at the advanced stage of the glycation. Carboxymethyllysine was significantly inhibited by the OLE but it showed weaker activity against argpyrimidine and carboxyethyllysine. The antiglycative activity of each OLE fraction independently did not explain the activity reached in the whole extract, being necessary the compounds present in both fractions. OLE and its fractions were highly effective for trapping reactive dicarbonyl compounds (glyoxal, methylglyoxal, 3-deoxyglucosone and 3-deoxygalactosone). Different adducts resulting from the conjugation of methylglyoxal and hydroxytyrosol in OLE were identified. Results pointed out that OLE exert a broad-spectrum in vitro antiglycative activity.

Section snippets

Chemical compounds

Hydroxytyrosol (PubChem CID: 82755)

3,4-dihydroxyphenylacetic acid (PubChem CID: 547)

Methylglyoxal (PubChem CID: 880)

Aminoguanidine (PubChem CID: 2146)

3-deoxyglucosone (PubChem CID: 114839)

3-deoxygalactosone (PubChem CID: 102601182);

Carboxymethyllysine (PubChem CID: 123800)

Carboxyethyllysine (PubChem CID: 23400779)

Argpyrimidine (PubChem CID: 75098600)

Chemicals

Olive leaves (Olea Europaea, Picual variety, Córdoba, Spain), d (+)-glucose (GLC), bovine serum albumin (BSA), methylglyoxal (MGO) and glyoxal (GO) (40% aqueous solution), pyridoxamine (PM), aminoguanidine (AG), 5-methylquinoxaline (5-MQ), nitrotetrazolium blue chloride (NBT), o-phenylenediamine (OPD), sodium borohydride, perfluoropentanoic acid (purity > 97%), heptafluorobutyric acid (HFBA) and standards of phenolic compounds were supplied by Sigma (St Louis, MO, USA). 3-deoxyglucosone (3-DG,

Identification of phenolic compounds in the extract

Thirty compounds were identified in the acid-treated OLE eluted at 12–24 min with an increasing ACN gradient from 25 to 57% (Fig. 1a). Chemical characterization involved high-resolution QTOF to determine the exact mass of each compound as confirmed by the MS/MS spectra, the NIST standard reference database and previously reported data (Kawaguchi et al., 2011, Peralbo-Molina et al., 2012, Quirantes-Piné et al., 2013). HT, oleuropein, rutin, verbascoside and tyrosol were further confirmed by

Conclusion

An OLE obtained under acidic conditions proved an effective inhibition of glycation under physiological conditions by hindering the formation of fluorescent AGEs and specific AGEs, such as CML, and in a lesser extent, CEL and ArgP. The antiglycative activity of OLE fractions separately did not explain the activity obtained for the whole extract. Although the compounds present in each fraction will contribute to the antiglycative activity, they could act synergistically to reach the highest rate

Funding

This work was funded by the Regional Government of Madrid and the European Regional Development Fund programme [S2013/ABI-3028-AVANSECAL], as well as by Spanish National Research Council [CSIC-201370E027]. M. Navarro was additionally supported by the JAE programme (Spanish National Research Council).

Conflict of interest

The authors declare no conflict of interest.

Acknowledgements

The authors thank Ms. I. Alvarez and Mr. M.A. Martinez for technical assistance, and Professor Monika Pischetsrieder for kindly supplying the standards of C6 dicarbonyl compounds.

References (28)

  • J.R. Baker et al.

    Chemistry of the fructosamine assay: D-glucosone is the product of oxidation of Amadori compounds

    Clinical Chemistry

    (1994)
  • D. Chandler et al.

    Effects of plant-derived polyphenols on TNF-a and nitric oxide production induced by advanced glycation endproducts

    Molecular Nutrition & Food Research

    (2010)
  • T. Hu et al.

    Hydroxytyrosol and its potential therapeutic effects

    Journal of Agricultural and Food Chemistry

    (2014)
  • K. Kawaguchi et al.

    Effects of antioxidant polyphenols on TNF-alpha-related diseases

    Current Topics in Medicinal Chemistry

    (2011)
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