iridoids and elenolic-acid

Olive fruit is a significant and promising source of potential bioactive compounds such as oleuropein and hydroxytyrosol. Oleuropein is the ester of elenolic acid and 3,4-dihydroxyphenyl ethanol (HT). It is the main glycoside in olives, the degradation of which results in the formation of hydroxytyrosol in olive oil. Both plays a significant role in the reduction of coronary heart diseases and a certain type of cancers. Both olive oil phenols have an effective role counter to cell proliferation, cell growth, migration, invasion, and angiogenesis. They down regulate the expression of BCL-2 and COX-2 proteins, and reduced DNA damage. Hydroxytyrosol and oleuropein inhibited the multiple stages in colon carcinogenesis; initiation, promotion, and metastasis. They also provide protection against various human cancers including colorectal, skin, breast, thyroid, digestive, lung, brain, blood, and cervical. This review article discusses the anticancer perspectives and mechanisms of oleuropein and hydroxytyrosol in cell cultures and animal and human studies.

Topics: Animals; Antineoplastic Agents; Cell Movement; Cell Proliferation; Coronary Disease; DNA Damage; Humans; Iridoid Glucosides; Iridoids; Neoplasm Invasiveness; Neoplasms; Neovascularization, Pathologic; Olea; Olive Oil; Phenylethyl Alcohol; Pyrans

The antimicrobial activity of phenolic compounds from Olea (O.) europaea Linné (L.) is part of the scientific discussion regarding the use of natural plant extracts as alternative food preservative agents. Although, the basic knowledge on the antimicrobial potential of certain molecules such as oleuropein, hydroxytyrosol or elenolic acid derivatives is given, there is still little information regarding their applicability for food preservation. This might be primarily due to the lack of information regarding the full antimicrobial spectrum of the compounds, their synergisms in natural or artificial combinations and their interaction with food ingredients. The present review accumulates available literature from the past 40 years, investigating the antimicrobial activity of O. europaea L. derived extracts and compounds in vitro and in food matrices, in order to evaluate their food applicability. In summary, defined extracts from olive fruit or leaves, containing the strongest antimicrobial compounds hydroxytyrosol, oleacein or oleacanthal in considerable concentrations, appear to be suitable for food preservation. Nonetheless there is still need for consequent research on the compounds activity in food matrices, their effect on the natural microbiota of certain foods and their influence on the sensorial properties of the targeted products.

Topics: Aldehydes; Anti-Infective Agents; Food Preservatives; Fruit; Iridoid Glucosides; Iridoids; Olea; Phenols; Phenylethyl Alcohol; Plant Extracts; Plant Leaves; Pyrans

The bitter taste of olives is mainly caused by the phenolic compound named oleuropein and the mechanism of its hydrolysis during the processing of natural green olives was studied. First, a rapid chemical hydrolysis of oleuropein takes place at a high temperature of 40°C and at a low pH value of 2.8, but the chemical hydrolysis of the bitter compound is slow at the common range of pH for these olives (3.8-4.2). However, decarboxymethyl elenolic acid linked to hydroxytyrosol and hydroxytyrosol have been found in a high concentration during the elaboration of natural green olives. When olives were heated at 90°C for 10min before brining, these compounds are not formed. Hence, the debittering process in natural green olives is due to the activity of β-glucosidase and esterase during the first months of storage and then a slow chemical hydrolysis of oleuropein happens throughout storage time.

Topics: beta-Glucosidase; Esterases; Food Handling; Food Storage; Hot Temperature; Hydrogen-Ion Concentration; Hydrolysis; Iridoid Glucosides; Iridoids; Olea; Phenols; Phenylethyl Alcohol; Pyrans; Salts; Taste

Oleuropein (OE), the main polyphenol in olive leaf extract, is likely to decompose into hydroxytyrosol (HT) and elenolic acid under the action of light, acid, base, high temperature. In the enzymatic process, the content of OE in olive leaf extract and enzyme are key factors that affect the yield of HT. A selective enzyme was screened from among 10 enzymes with a high OE degradation rate. A single factor (pH, temperature, time, enzyme quantity) optimization process and a Box-Behnken design were studied for the enzymatic hydrolysis of 81.04% OE olive leaf extract. Additionally, enzymatic hydrolysis results with different substrates (38.6% and 81.04% OE) were compared and the DPPH antioxidant properties were also evaluated. The result showed that the performance of hydrolysis treatments was best using hemicellulase as a bio-catalyst, and the high purity of OE in olive extract was beneficial to biotransform OE into HT. The optimal enzymatic conditions for achieving a maximal yield of HT content obtained by the regression were as follows: pH 5, temperature 55 °C and enzyme quantity 55 mg. The experimental result was 11.31% ± 0.15%, and the degradation rate of OE was 98.54%. From the present investigation of the antioxidant activity determined by the DPPH method, the phenol content and radical scavenging effect were both decreased after enzymatic hydrolysis by hemicellulase. However, a high antioxidant activity of the ethyl acetate extract enzymatic hydrolysate (IC50 = 41.82 μg/mL) was demonstated. The results presented in this work suggested that hemicellulase has promising and attractive properties for industrial production of HT, and indicated that HT might be a valuable biological component for use in pharmaceutical products and functional foods.

Topics: Antioxidants; Biotransformation; Hydrolysis; Iridoid Glucosides; Iridoids; Olea; Phenylethyl Alcohol; Plant Extracts; Plant Leaves; Pyrans

With the aim to enhance characterization of virgin olive oil (VOO), high resolution mass spectrometry (HRMS) and high resolution tandem mass spectrometry (HRMS/MS), in positive and negative electrospray ionization (ESI) modes, coupled to fused-core reverse phase chromatography, were applied to distinct VOO phenolic extracts after the optimization of chromatographic conditions, ESI and fragmentation parameters. HRMS, but also HRMS/MS resulted fundamental to progress in secoiridoids structural elucidation. The former revealed that the secoiridoid composition of VOO was far more complicated than previously reported, while the latter helped clarify product ion elemental composition allowing new fragmentations, in addition to those reported in the literature, to be put forward. In particular, for the first time, different product ions with the same nominal mass were unequivocally identified in the spectra of secoiridoid compounds, confirming the greater capacity of HRMS/MS to clarify structure than low-resolution MS. Furthermore, and differing from previous studies, the multiple isomers of the main VOO secoiridoids could be differentiated on the basis of their HR product ion spectra in positive mode.

Topics: Chromatography, Reverse-Phase; Glucosides; Iridoid Glucosides; Iridoids; Isomerism; Olive Oil; Oxygen; Plant Oils; Pyrans; Tandem Mass Spectrometry

In this work, high-performance liquid chromatography (HPLC) coupled to electrospray time-of-flight mass spectrometry (ESI-TOF-MS) and electrospray ion trap multiple-stage tandem mass spectrometry (ESI-IT-MS(2)) has been applied to screen phenolic compounds in olive leaf extracts. The use of a small particle size C18 column (1.8 micro) provided great resolution and made separation of a lot of isomers possible. The structural characterization was based on accurate mass data obtained by ESI-TOF-MS, and the nature of fragmentation ions were further confirmed by ESI-IT-MS(2) when possible. In addition, we employed tetrazolium salt (MTT)-based assays to assess the effects of olive leaf extracts on the growth of human tumor-derived cells. Upon this approach, we achieved an accurate profile of olive leaf phenolics along with the identification of several important isomers of secoiridoids and flavonoids. This will allow a better understanding of the complete composition of olive-leaf-bioactive compounds as well as their involvement in Olea europaea L. biochemical pathways. Importantly, olive leaf extracts exhibited dose-dependent inhibitory effects on the metabolic status (cell viability) of three breast cancer models in vitro. Since the tumoricidal activity of the extracts should be mainly attributed to the identified olive leaf phenolics, these findings warrant further investigation at the structure-function molecular level to definitely establish the anticancer value of these phytochemicals.

Topics: Antineoplastic Agents, Phytogenic; Breast Neoplasms; Carcinoma; Cell Survival; Chromatography, High Pressure Liquid; Cinnamates; Female; Flavonoids; Humans; Iridoid Glucosides; Iridoids; Olea; Phenols; Plant Leaves; Pyrans; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

Recent experimental study found that OLE (olive leaf extract) has anti-HIV activity by blocking the HIV virus entry to host cells [Lee-Huang, S., Zhang, L., Huang, P.L., Chang, Y. and Huang, P.L. (2003) Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment. Biochem. Biophys. Res. Commun. 307, 1029; Lee-Huang, S., Huang, P.L., Zhang, D., Lee, J.W., Bao, J., Sun, Y., Chang, Y.-Tae, Zhang, J.Z.H. and Huang, P.L. (2007) Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol. Biochem. Biophys. Res. Commun. 354, 872-878, 879-884]. As part of a joint experimental and theoretical effort, we report here computational study to help identify and characterize the binding complexes of several main compounds of OLE (olive leaf extract) to HIV-1 envelop protein gp41. A number of possible binding modes are found by docking oleuropein and its metabolites, aglycone, elenolic acid and hydroxytyrosol, onto the hydrophobic pocket on gp41. Detailed OLE-gp41 binding interactions and free energies of binding are obtained through molecular dynamics simulation and MM-PBSA calculation. Specific molecular interactions in our predicted OLE/gp41 complexes are identified and hydroxytyrosol is identified to be the main moiety for binding to gp41. This computational study complements the corresponding experimental investigation and helps establish a good starting point for further refinement of OLE-based gp41 inhibitors.

Topics: Antiviral Agents; Computer Simulation; HIV Envelope Protein gp41; HIV-1; Humans; Hydrogen Bonding; Iridoid Glucosides; Iridoids; Models, Molecular; Molecular Structure; Olea; Phenylethyl Alcohol; Plant Extracts; Plant Leaves; Protein Binding; Pyrans; Thermodynamics

The inhibitors involved in the lactic acid fermentation of table olives were investigated in aseptic olive brines of the Manzanilla and Gordal varieties. Phenolic and oleosidic compounds in these brines were identified by high-performance liquid chromatography with ultraviolet and electrospray ionization mass spectrometry detection, and several substances were also characterized by nuclear magnetic resonance. Among these compounds, the dialdehydic form of decarboxymethyl elenolic acid linked to hydroxytyrosol showed the strongest antilactic acid bacteria activity, and its presence in brines could explain the growth inhibition of these microorganisms during olive fermentation. However, it was found that the dialdehydic form of decarboxymethyl elenolic acid, identified for the first time in table olives, and an isomer of oleoside 11-methyl ester were also effective against Lactobacillus pentosus and can, therefore, contribute to the antimicrobial activity of olive brines. It must also be stressed that the three new inhibitors discovered in table olive brines exerted a more potent antibacterial activity than the well-studied oleuropein and hydroxytyrosol.

Topics: Anti-Bacterial Agents; Chromatography, High Pressure Liquid; Fermentation; Iridoid Glucosides; Iridoids; Lactobacillus; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Olea; Phenylethyl Alcohol; Pyrans; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Ultraviolet

A capillary zone electrophoresis method has been carried out to determine and quantitate some compounds of the polyphenolic fraction of virgin olive oil which have never previously been determined before using capillary electrophoresis, such as elenolic acid, ligstroside aglycon, oleuropein aglycon, and (+)-pinoresinol. The compounds were identified using standards obtained by semipreparative high-performance liquid chromatography (HPLC). A detailed method optimization was performed to separate the phenolic compounds present in olive oil using a methanol-water extract of Picual extra-virgin olive oil, and different extraction systems were compared (C18-solid phase extraction (SPE), Diol-SPE, Sax-SPE and liquid-liquid extraction). The optimized parameters were 30 mM sodium tetraborate buffer (pH 9.3) at 25 kV with 8 s hydrodynamic injection, and the quantitation was carried out by the use of two reference compounds at two different wavelengths.

Topics: Chromatography, High Pressure Liquid; Electrophoresis, Capillary; Flavonoids; Furans; Glucosides; Iridoid Glucosides; Iridoids; Lignans; Olive Oil; Phenols; Phenylethyl Alcohol; Plant Oils; Polyphenols; Pyrans

Epidemiology suggests that Mediterranean diets are associated with reduced risk of cardiovascular disease. Because monocyte adhesion to the endothelium is crucial in early atherogenesis, we evaluated whether typical olive oil and red wine polyphenols affect endothelial-leukocyte adhesion molecule expression and monocyte adhesion.. Phytochemicals in olive oil and red wine, including oleuropein, hydroxytyrosol, tyrosol, elenolic acid, and resveratrol, with or without antioxidant activity, were incubated with human umbilical vein endothelial cells for 30 minutes, followed by co-incubation with bacterial lipopolysaccharide or cytokines to trigger adhesion molecule expression. At nutritionally relevant concentrations, only oleuropein, hydroxytyrosol, and resveratrol, possessing a marked antioxidant activity, reduced monocytoid cell adhesion to stimulated endothelium, as well as vascular cell adhesion molecule-1 (VCAM-1) mRNA and protein by Northern analysis and cell surface enzyme immunoassay. Reporter gene assays with deletional VCAM-1 promoter constructs indicated the relevance of nuclear factor-kappaB, activator protein-1, and possibly GATA binding sites in mediating VCAM-1 transcriptional inhibition. The involvement of nuclear factor-kappaB and activator protein-1 was finally demonstrated at electrophoretic mobility shift assays.. Olive oil and red wine antioxidant polyphenols at nutritionally relevant concentrations transcriptionally inhibit endothelial adhesion molecule expression, thus partially explaining atheroprotection from Mediterranean diets.

Topics: Animals; Antioxidants; Arteriosclerosis; Cattle; Cell Adhesion; Cells, Cultured; Diet; Endothelium, Vascular; Flavonoids; Gene Expression Regulation; Humans; Iridoid Glucosides; Iridoids; NF-kappa B; Olive Oil; Phenols; Phenylethyl Alcohol; Plant Oils; Polyphenols; Pyrans; Resveratrol; RNA, Messenger; Stilbenes; Transcription Factor AP-1; Transcription, Genetic; U937 Cells; Vascular Cell Adhesion Molecule-1; Wine

This study presents the phenolic compounds profile of commercial Cornicabra virgin olive oils from five successive crop seasons (1995/1996 to 1999/2000; n = 97), determined by solid phase extraction reversed phase high-performance liquid chromatography (SPE RP-HPLC), and its relationship with oxidative stability, processing conditions, and a preliminary study on variety classification. The median of total phenols content was 38 ppm (as syringic acid), although a wide range was observed, from 11 to 76 ppm. The main phenols found were the dialdehydic form of elenolic acid linked to tyrosol (p-HPEA-EDA; 9 +/- 7 ppm, as median and interquartile range), oleuropein aglycon (8 +/- 6 ppm), and the dialdehydic form of elenolic acid linked to hydroxytyrosol (3,4-DHPEA-EDA; 5 +/- 8 ppm). In many cases the correlation with oxidative stability was higher when the sum of the dialdehydic form of elenolic acid linked to hydroxytyrosol (3,4-DHPEA-EDA) and oleuropein aglycon (r (2) = 0.91-0.96) or the sum of these two and hydroxytyrosol (r (2) = 0.90-0.97) was considered than was observed with HPLC total phenols (r (2)= 0.91-0.95) and especially with colorimetric determination of total polyphenols and o-diphenols (r (2) = 0.77-0.95 and 0.78-0.92, respectively). 3,4-DHPEA-EDA, p-HPEA-EDA, the aglycons of oleuropein and ligstroside, and HPLC total phenols content presented highly significant differences (p = 0.001-0.010) with respect to the dual- and triple-phase extraction systems used, whereas colorimetric total polyphenols content did not (p = 0.348) and o-diphenols showed a much lower significant difference (p = 0.031). The five variables that most satisfactorily classified the principal commercial Spanish virgin olive oil varieties were 1-acetoxypinoresinol, 4-(acetoxyethyl)-1,2-dihydroxybenzene (3,4-DHPEA-AC), ligstroside aglycon, p-HPEA-EDA, and RT 43.3 contents.

Topics: Chromatography, High Pressure Liquid; Colorimetry; Drug Stability; Flavonoids; Iridoid Glucosides; Iridoids; Olive Oil; Oxidation-Reduction; Phenols; Phenylethyl Alcohol; Plant Oils; Polymers; Polyphenols; Pyrans; Seasons