On the Oleuropein, the Bitter Principle of Olives 1

J. Am. Soc. Mass Spectrom.

Bergquist

Markides

et al. 2008

Abnormal accumulation and aggregation of amyloid-␤-peptide (A␤) eventually lead to the formation and cerebral deposition of amyloid plaques, the major pathological hallmark in Alzheimer's disease (AD). Oleuropein (OE), an Olea europaea L. derived polyphenol, exhibits a broad range of pharmacological properties, such as antioxidant, anti-inflammatory, and antiatherogenic, which could serve as combative mechanisms against several reported pathways involved in the pathophysiology of AD. The reported noncovalent interaction between A␤ and OE could imply a potential antiamyloidogenic role of the latter on the former via stabilization of its structure and prevention of the adaptation of a toxic ␤-sheet conformation. The established ␤-sheet conformation of the A␤ hydrophobic carboxy-terminal region and the dependence of its toxicity and aggregational propensity on its secondary structure make the determination of the binding site between A␤ and OE highly important for assessing the role of the interaction. In this study, two different proteolytic digestion protocols, in conjunction with high-sensitivity electrospray ionization mass spectrometric analysis of the resulting peptide fragments, were used to determine the noncovalent binding site of OE on A␤ and revealed the critical regions for the interaction. and its aggregational properties depend on both the peptide concentration and conformation, as well as on the solution conditions and pH [2,3]. It has been reported that reduction of the A␤ production, by controlling the cleavage of the larger transmembrane amyloid precursor protein (APP), or inhibition of its aggregation by using small molecules, which may interact noncovalently with A␤ and stabilize its structure, could serve as preventive or therapeutic approaches against AD [4]. In general, interruption of noncovalent interactions between protein and peptides, or even more between proteins/peptides and ligands can cause abnormalities, which often lead to diseases [5]. One interaction of this kind has been established between the Olea europaea derived bioactive compound, oleuropein (OE), and A␤ by means of electrospray ionization mass spectrometry (ESI-MS) [6]. This interaction could prove potent in inhibiting its aggregation.OE is a polyphenol extracted from the fruits and leaves of Olea europaea L. and possesses a wide range of pharmacological properties, such as antioxidant [7][8][9], anti-inflammatory [10, 11], antiatherogenic [12-14], antibacterial [15][16][17], and anticancer [18,19]. Moreover, OE and its metabolites have been shown to be potent against contemporary diseases, such as HIV [20,21] and osteoporosis [22,23]. Interestingly, in vitro [24] and epidemiological [25] studies demonstrated the positive impact of polyphenols on the onset of age-related disorders, such as dementia [26,27].It is regarded that the pathophysiology of AD is tangled and many theories have been proposed to illumine its mechanism. Free radical reactions and oxidative stress [28,29], as well as unregulated immune response [30,3...

Section: Resultsmentioning

confidence: 99%

Section: Sample Preparationmentioning

confidence: 99%

Localization of the noncovalent binding site between amyloid-β-peptide and oleuropein using electrospray ionization FT-ICR mass spectrometry

J. Am. Soc. Mass Spectrom.

Bergquist

Markides

et al. 2008

“…OE and EA were isolated from olive tree (O. europea, var. Koroneiki) leaves (Shasha and Leibowitz, 1961;Gariboldi et al, 1986) and were generously donated from the Division of Pharmacognosy and Natural Products Chemistry, School of Pharmacy, University of Athens. The purity of all organic substances used was checked by HPLC and NMR prior to their use and was greater than 99%.…”

Section: Reagents and Chemicalsmentioning

confidence: 99%

Simultaneous quantification of oleuropein and its metabolites in rat plasma by liquid chromatography electrospray ionization tandem mass spectrometry

Biomedical Chromatography

Gikas

Tsarbopoulos

2009

Oleuropein (OE) is the cardinal bioactive compound derived from Olea europaea and possesses numerous beneficial properties for human health. However, despite the plethora of analytical methods that have studied the biological fate of olive oil-derived bioactive compounds, no validated methodology has been published to date for the simultaneous determination of OE, along with all its major metabolites. In this study, a liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI MS/MS) method has been developed and validated for the quantification of OE, simultaneously with its main metabolites hydroxytyrosol, 2-(3,4-dihydroxyphenyl)acetic acid, 4-(2-hydroxyethyl)-2-methoxy-phenol or homovanillyl alcohol, 2-(4-hydroxy-3-methoxyphenyl)acetic acid or homovanillic acid, and elenolic acid in rat plasma matrix. Samples were analyzed by LC-ESI MS/MS prior to and after enzymatic treatment. A solid-phase extraction step with high mean recovery for all compounds was performed as sample pretreatment. Calibration curves were linear for all bioactive compounds over the range studied, while the method exhibited good accuracy, intra- and inter-day precision. The limit of detection was in the picogram range (per milliliterof plasma) for HT and OE and in the nanogram range (per milliliter of plasma) for the other analytes, and the method was simple and rapid. The developed methodology was successfully applied for the simultaneous quantification of OE and its aforementioned metabolites in rat plasma samples, thus demonstrating its suitability for pharmacokinetics, as well as bioavailability and metabolism studies.

“…OE was isolated from the leaves of Olea europea var. koroneiki, according to a previously described procedure [42] with greater than 99% purity, as it was assessed by NMR analysis. All solvents used were of analytical grade purity.…”

Section: Sample Preparationmentioning

confidence: 99%

Noncovalent interaction between amyloid-β-peptide (1–40) and oleuropein studied by electrospray ionization mass spectrometry

J. Am. Soc. Mass Spectrom.

Bergquist

Markides

et al. 2006

Beta amyloid peptide (Abeta) is the major proteinaceous component of senile plaques formed in Alzheimer's disease (AD) brain. The aggregation of Abeta is associated with neurodegeneration, loss of cognitive ability, and premature death. It has been suggested that oxidative stress and generation of free radical species have implications in the fibrillation of Abeta and its subsequent neurotoxicity. For this reason, it is proposed that antioxidants may offer a protective or therapeutic alternative against amyloidosis. This study is the first report of the formation of the noncovalent complex between Abeta or its oxidized form and the natural derived antioxidant oleuropein (OE) by electrospray ionization mass spectrometry (ESI MS). ESI MS allowed the real time monitoring of the complex formation between Abeta, OE, and variants thereof. Several experimental conditions, such as elevated orifice potential, low pH values, presence of organic modifier, and ligand concentration were examined, to assess the specificity and the stability of the formed noncovalent complexes.