A method based on high-performance liquid chromatography (HPLC) with a diode array detection system was developed and validated aiming at the simultaneous determination of oleuropein (OE) and its metabolites, hydroxytyrosol (HT) and tyrosol (T), in human plasma. These phenolic components are believed to play a vital role in the prevention of coronary artery disease and atherosclerosis. The proposed method includes a clean-up solid-phase extraction procedure (using a C(18) column) with high recovery efficiency (85-100%). The statistical evaluation of the method reveals good linearity, accuracy and reproducibility for all the compounds analyzed with RSD values less than 6.5%, while the detection limit is 50 ng/ml for both OE and T and 75 ng/ml for HT. This assay can be employed in bioavailability studies of olive oil phenolic compounds, thus assisting the evaluation of their pharmacological role.

A current trend in olive mill wastewater (OMWW) management is to not only decrease environmental pollution but also to extract and utilize valuable by-products. Therefore, the objectives of this study were to explore different techniques for drying a phenolic-rich membrane filtration fraction of OMWW and compare the techniques in terms of the dried product quality and feasibility of the process. The OMWW from 2 (3-phase and 2-phase) California mills was subjected to a 2-step membrane filtration process using a novel vibratory system. The reverse osmosis retentate (RO-R) is a phenolic-rich coproduct stream, and the reverse osmosis permeate is a near-pure water stream that could be recycled into the milling process. Spray-, freeze-, and infrared-drying were applied to obtain solid material from the RO-R. Drying of the RO-R was made possible only with addition of 10% maltodextrin as a carrier. The total soluble phenolics in dried RO-R were in the range 0.15 to 0.58 mg gallic acid equivalents/g of dry weight for 2-phase RO-R, and 1.38 to 2.17 mg gallic acid equivalents/g of dry weight for the 3-phase RO-R. Spray-dried RO-R from 3-phase OMWW showed remarkable antioxidant activity. Protocatechuic acid, tyrosol, vanillic acid, and p-coumaric acid were quantified in all dried RO-R, whereas 3-hydroxytyrosol was found in 3-phase dried RO-R. This combination of separation and drying technologies helps to add value and shelf-stability to an olive oil by-product and increase environmental sustainability of its production.

Seven new polyketides, phomaketides A-E (1-5) and pseurotins A3 (6) and G (7), along with the known compounds FR-111142, pseurotins A, A1, A2, D, and F2, 14-norpseurotin A, α-carbonylcarbene, tyrosol, cyclo(-l-Pro-l-Leu), and cyclo(-l-Pro-l-Phe), were purified from the fermentation broth and mycelium of the endophytic fungal strain Phoma sp. NTOU4195 isolated from the marine red alga Pterocladiella capillacea. The structures were established through interpretation of spectroscopic data. The antiangiogenic and anti-inflammatory effects of 1-7 and related analogues were evaluated using human endothelial progenitor cells (EPCs) and lipopolysaccharide (LPS)-activated murine macrophage RAW264.7 cells, respectively. Of the compounds tested, compound 1 exhibited the most potent antiangiogenic activity by suppressing the tube formation of EPCs with an IC50 of 8.1 μM, and compound 3 showed the most selective inhibitory activity of LPS-induced NO production in RAW264.7 macrophages with an IC50 value of 8.8 μM.

An analytical method for the simultaneous determination of hydroxytyrosol and tyrosol in different types of olive extract raw materials and cosmetic cream samples has been developed. The determination was performed by liquid chromatography with UV spectrophotometric detection. Different chromatographic parameters, such as mobile phase pH and composition, oven temperature and different sample preparation variables were studied. The best chromatographic separation was obtained under the following conditions: C18 column set at 35°C and isocratic elution of a mixture ethanol: 1% acetic acid solution at pH 5 (5:95, v/v) as mobile phase pumped at 1 mL min(-1). The detection wavelength was set at 280 nm and the total run time required for the chromatographic analysis was 10 min, except for cosmetic cream samples where 20 min runtime was required (including a cleaning step). The method was satisfactorily applied to 23 samples including solid, water-soluble and fat-soluble olive extracts and cosmetic cream samples containing hydroxytyrosol and tyrosol. Good recoveries (95-107%) and repeatability (1.1-3.6%) were obtained, besides of limits of detection values below the μg mL(-1) level. These good analytical features, as well as its environmentally-friendly characteristics, make the presented method suitable to carry out both the control of the whole manufacture process of raw materials containing the target analytes and the quality control of the finished cosmetic products.

A gas chromatographic-mass spectrometric (GC-MS) method for qualitative and subsequent quantitative analysis of phenolic antioxidants compounds, presents in olive oil, in rat cerebrospinal fluid (CSF) after oral administration of compounds is proposed. The procedure involves the extraction of compounds from the samples by a traditional microliquid-liquid extraction method, followed by a silylation step before the GC-MS analysis. The chromatographic separation was performed by using a low bleed DB5-MS fused-silica capillary column. The presence of 21 phenolic compounds was tested in CSF extracts and only free tyrosol, hydroxytyrosol and ferulic acid were detected. Those compounds were then quantitatively determined using the proposed methology. The molecular ion for silylated compounds appears at 370 m/z for hydroxytyrosol, 282 m/z for tyrosol and 338 m/z for ferulic acid respectively, while the base peak appears at 267 m/z, 179 m/z and 338 m/z. alpha-Naphthol was used as a surrogate (216 and 201 m/z). The detection capabilities obtained were 74, 92 and 79 ng/mL respectively. The method was applied to the determination of trace amounts of compounds in rat cerebrospinal fluid after oral administration. The animals were fed with a standard chow diet (free of phenolic antioxidants) in order to avoid the influence of any other component of the diet on the CSF of the animals.

We report results from a detailed computer simulation study for the nano-sorption and mobility of four different small molecules (water, tyrosol, vanillic acid, and p-coumaric acid) inside smooth single-wall carbon nanotubes (SWCNTs). Most of the results have been obtained with the molecular dynamics (MD) method, but especially for the most narrow of the CNTs considered, the results for one of the molecules addressed here (water) were further confirmed through an additional Grand Canonical (μVT) Monte Carlo (GCMC) simulation using a value for the water chemical potential μ pre-computed with the particle deletion method. Issues addressed include molecular packing and ordering inside the nanotube for the four molecules, average number of sorbed molecules per unit length of the tube, and mean residence time and effective axial diffusivities, all as a function of tube diameter and tube length. In all cases, a strong dependence of the results on tube diameter was observed, especially in the way the different molecules are packed and organized inside the CNT. For water for which predictions of properties such as local structure and packing were computed with both methods (MD and GCMC), the two sets of results were found to be fully self-consistent for all types of SWCNTs considered. Water diffusivity inside the CNT (although, strongly dependent on the CNT diameter) was computed with two different methods, both of which gave identical results. For large enough CNT diameters (larger than about 13 Å), this was found to be higher than the corresponding experimental value in the bulk by about 55%. Surprisingly enough, for the rest of the molecules simulated (phenolic), the simulations revealed no signs of mobility inside nanotubes with a diameter smaller than the (20, 20) tube. This is attributed to strong phenyl-phenyl attractive interactions, also to favorable interactions of these molecules with the CNT walls, which cause them to form highly ordered, very stable structures inside the nanotube, especially under strong confinement. The interaction, in particular, of the methyl group (present in tyrosol, vanillic acid, and p-coumaric acid) with the CNT walls seems to play a key role in all these compounds causing them to remain practically immobile inside nanotubes characterized by diameters smaller than about 26 Å. It is only for larger-diameter CNTs that tyrosol, vanillic acid, and p-coumaric acid were observed to demonstrate appreciable mobility.

BACKGROUND

Aculus olearius Castagnoli is a recently recorded species that damages olive fruits in the Mediterranean basin of Turkey. Thus, the effects of Eriophyid mites (Aculus olearius Castagnoli and Aceria oleae (Nalepa) (Acarina: Eriophyidae) on the olive fruits from Ayvalık variety in southern Turkey were studied for the first time in terms of some physical parameters and chemical constituents including some individual phenolics.

RESULTS

The Eriophyid damaged fruits had higher L* values (lighter colour) and tyrosol level (37.53 mg kg(-1) ) than the undamaged fruits (28.51 mg kg(-1) ) in August. In contrast, Eriophyid damaged fruits were darker in colour and had lower levels (25.77 mg kg(-1) ) of tyrosol than those of undamaged fruits (79.14 mg kg(-1) ) in October. Eriophyid damaged samples had higher values of vanillic acid than the undamaged samples. An increase in the average concentrations of hydroxytyrosol and p-coumaric acid was observed in the fruits harvested in August, whilst the oleuropein content decreased.

CONCLUSIONS

The harvest in October can be recommended regarding the higher dimensional values, total oil, dry matter and oleuropein contents. But the interaction between harvest time and Eriophyid damage was found effective in terms of tyrosol content and skin colour; as tyrosol values were lower in the fruits harvested in October and the fruits were darker. The resistance of undamaged fruits against Eriophyid damage can be linked to high tyrosol content of these fruits.

Extra virgin olive oil (EVOO) and red wine (RW) are two basic elements that form part of the so-called Mediterranean diet. Both stand out because of their high phenolic compound content and their potential related health benefits. The present study is focused on the metabolic disposition of resveratrol (RESV), tyrosol (TYR), and hydroxytyrosol (HT) following the consumption of EVOO, RW, and a combination of both. In this study, 12 healthy volunteers consumed a single dose of 25 mL of EVOO, 150 mL of RW, and a combination of both in a crossover randomized clinical trial. Urinary recovery of RESV, TYR, and HT was analysed in urine samples collected over a 6-h period following the intake of each treatment. Higher HT levels were observed following EVOO compared to RW (3788 ± 1751 nmols and 2308 ± 847 nmols respectively). After the combination of EVOO and RW, the recovery of TYR and HT metabolites increased statistically compared to their separate consumption (4925 ± 1751 nmols of TYR and 6286 ± 3198 nmols of HT). EVOO triggered an increase in glucuronide conjugates, while RW intake raised sulfate metabolites. Marginal effects were observed in RESV increased bioavailability after the combination of RW with the fat matrix provided by EVOO.

Alongside the French paradox, the REGICOR Study (Girona, Spain) has shown another paradox in the Mediterranean area: a high prevalence of cardiovascular risk factors with low incidence of myocardial infarction in the population of Girona, Spain. The antioxidant effects associated with olive oil consumption could explain part of this 'Mediterranean Paradox'. Virgin olive oils processed by two centrifugation phases and with low fruit ripeness have the highest levels of antioxidant content. The total content of phenolic compounds (PC) from virgin olive oil could delay LDL oxidation. The content and nature of olive oil PC have a high influence in the antioxidant capacity of an olive oil. PC from diet could bind human LDL in non-supplemented volunteers. PC from virgin olive oil could bind LDL and tyrosol is bioavailable in humans from ingestion of virgin olive oil in its natural form.

Endophyte is a factor that affects the physiology and metabolism of plant. However, limited information is available on the mechanism of interaction between endophyte and plant. To investigate the effects of endophytic fungus ZPRs-R11, that is, Trimmatostroma sp., on salidroside and tyrosol accumulations in Rhodiola crenulata, signal transduction, enzyme gene expression, and metabolic pathway were investigated. Results showed that hydrogen peroxide (H2O2), nitric oxide (NO), and salicylic acid (SA) involved in fungus-induced salidroside and tyrosol accumulations. NO acted as an upstream signal of H2O2 and SA. No up- or down-stream relationship was observed, but mutual coordination existed between H2O2 and SA. Rate-limiting enzyme genes with the maximum expression activities were UDP-glucosyltransferase, tyrosine decarboxylase (TYDC), monoamine oxidase, phenylalanine ammonialyase (PAL), and cinnamic-4-hydroxylase sequentially. Nevertheless, the genes of tyrosine transaminase and pyruvate decarboxylase only indicated slightly higher activities than those in control. Thus, TYDC and PAL branches were the preferential pathways in ZPRs-R11-induced salidroside and tyrosol accumulation. Trimmatostroma sp. was a potential fungus for promoting salidroside and tyrosol accumulations. The present data also provided scientific basis for understanding complex interaction between endophytic fungus and R. crenulata.

The activation of signals in fluorescent nanosensors upon interaction with their targets is highly desirable. To this aim, several molecularly imprinted nanogels have been synthetized for the recognition of tyrosol, hydroxytyrosol and oleuropein in aqueous extracts using the non-covalent approach. Two of them contain fluorescein derivatives as co-monomers, and their fluorescence emission is switched on upon binding of the target phenols. The selection of functional monomers was previously done by analyzing the interactions by nuclear magnetic resonance (NMR) in deuterated dimethylsulfoxide (DMSO-d₆) of the monomers with tyrosol and hydroxytyrosol. Polymers were synthetized under high dilution conditions to obtain micro- and nano-particles, as verified by transmission electron microscopy (TEM). 1,4-Divinylbenzene (DVB) was used in the fluorescent polymers in order to enhance the interactions with the aromatic ring of the templates tyrosol and hydroxytyrosol by π-π stacking. The results were fully satisfactory as to rebinding: DVB-crosslinked molecularly imprinted polymers (MIPs) gave over 50 nmol/mg rebinding. The sensitivity of the fluorescent MIPs was excellent, with LODs in the pM range. The sensing polymers were tested on real olive leaves extracts, with very good performance and negligible matrix effects.

Keywords: fluorescence; imprinted nanogel; olive leaf extracts; phenols.

Τoward a harmonized and standardized procedure for the determination of total hydroxytyrosol and tyrosol content in virgin olive oil (VOO), the pros of a recently published in house validated ultra high performance liquid chromatography (UHPLC) protocol are discussed comparatively with those of other procedures that determine directly or indirectly the compounds hosted under the health claim on "olive oil polyphenols" (EC regulation 432/2012). Authentic VOOs were analyzed with five different liquid chromatographic separation protocols and ¹H-NMR one in five different laboratories with expertise in VOO phenol analysis within three months. Data comparison indicated differences in absolute values. Method comparison using appropriate tools (Passing-Bablok regression and Bland Altman analyses) for all protocols vs. the UHPLC one indicated slight or statistically significant differences. The results were also discussed in terms of cost effectiveness, detection means, standard requirements and ways to calculate the total hydroxytyrosol and tyrosol content. Findings point out that the in-house validated fit for the purpose UHPLC protocol presents certain pros that should be exploited by the interested parties. These are the simplicity of sample preparation, fast elution time that increase the number of samples analyzed per day and integration of well-resolved peaks with the aid of only two commercially available external standards. Importance of correction factors in the calculations is stressed.

A simple screening method for discrimination between commercial extra virgin olive oils and their blends with other vegetable oils was developed. Squalene, which was contained relatively high amounts in virgin olive oil, was determined by HPLC after a simple pretreatment that was carried out by dilution of oil samples with 2-propanol. Tyrosol, which was contained at relatively high concentration in virgin olive oil among phenolic compounds, was determined by HPLC after a simple liquid-liquid extraction. When using squalene and tyrosol contents as axes, extra virgin olive oils could be discriminated from pure olive oils, blended oils (extra virgin olive oils with sunflower oil or grapeseed oil) and other vegetable oils. These results suggest that determining squalene and tyrosol in seed oil samples could be useful in distinguishing between extra virgin olive oil and blended oils as a screening method.

Keywords: HPLC; adulteration; extra virgin olive oil; squalene; tyrosol.

In experiments on rats with left coronary artery occlusion, p-tyrosol (20 mg/kg, intravenously) showed the ability to decrease myocardial electric instability in phase 1b of ventricular arrhythmias: a fraction of rats without arrhythmia was increased by 36%, and the mean value of ventricular arrhythmia index exhibited a 3-fold decrease.

We demonstrated in experiments on rats with left coronary artery occlusion that intravenous administration of 20 mg/kg n-tyrosol during ischemia limited manifestations of oxidative stress in myocardial tissue during early post reperfusion period: content of diene and triene conjugates lowered 16 and 20%, respectively. This was associated with higher preservation of cardiomyocytes and reduction of the infarction zone.

Disposal of organic plant wastes and by-products from the food or pharmaceutical industries usually involves high costs. In the present study, 42 samples derived from such by-products were screened in vitro against Cryptosporidium parvum, a protozoan parasite that may contaminate drinking water and cause diarrhoea. The novel bioassay was previously established in the microtitre plate format. Human ileocaecal adenocarcinoma (HCT-8) cell cultures were seeded with C. parvum oocysts and parasite development was monitored by an indirect fluorescent antibody technique (IFAT) and microscopic assessment for clusters of secondary infection (CSI). Minimum inhibitory concentrations (MICs) and potential detrimental effects on the host cells were determined. An ethanolic extract from olive (Olea europaea) pomace, after oil pressing and phenol recovery, reproducibly inhibited C. parvum development (MIC = 250-500 μg mL(-1), IC50 = 361 (279-438) μg mL(-1), IC90 = 467 (398-615) μg mL(-1)). Accordingly, tyrosol, hydroxytyrosol, trans-coniferyl alcohol and oleuropein were selected as reference test compounds, but their contributions to the observed activity of the olive pomace extract were insignificant. The established test system proved to be a fast and efficient assay for identifying anti-cryptosporidial activities in biological waste material and comparison with selected reference compounds.

Metabolic engineering of Saccharomyces cerevisiae for high level production of aromatic chemicals has received increasing attention in recent years. Tyrosol production from glucose by S. cerevisiae is considered an environmentally sustainable and safe approach. However, the production of tyrosol and salidroside by engineered S. cerevisiae has been reported to be lower than 2 g/L to date. In this study, S. cerevisiae was engineered with a push-pull-restrain strategy to efficiently produce tyrosol and salidroside from glucose. The biosynthetic pathways of ethanol, phenylalanine and tryptophan were restrained by disrupting PDC1, PHA2 and TRP3. Subsequently, tyrosol biosynthesis was enhanced with a metabolic pull strategy of introducing PcAAS and EcTyrA^M53I/A354V . Moreover, a metabolic push strategy was implemented with the heterologous expression of phosphoketolase (Xfpk), and then Erythrose 4-phosphate was synthesized simultaneously by two pathways, the Xfpk-based pathway and the pentose phosphate pathway, in S. cerevisiae. Furthermore, the heterologous expression of Xfpk alone in S. cerevisiae efficiently improved tyrosol production compared with the coexpression of Xfpk and phosphotransacetylase. Finally, the tyrosol yield increased by approximately 135-folds, compared with that of parent strain. The total amount of tyrosol and salidroside with glucose fed-batch fermentation was over 10 g/L and reached levels suitable for large-scale production. This article is protected by copyright. All rights reserved.

Candida albicans is generally one of the most commonly isolated fungal pathogen from human body. It is a frequent cause of nosocomial infections, bloodstream infections, urinary infections and mucosal infections of oral cavity and vagina C. albicans can grow as hyphae, pseudohyphae, or budding yeast. Morphological conversion of a yeast form to pseudohyphal or hyphal one is often characterized by the change of commensal status to an invasive form. Farnesol and tyrosol can participate in these transformation processes as quorum sensing molecules together with some physical-chemical factors. A new analytical method for identification and quantification of biologically active substances farnesol and tyrosol using ultra high performance liquid chromatography (UHPLC) in connection with tandem mass spectrometry was developed. The analytes were separated on Acquity BEH C18 analytical column using binary mobile phase consisting of acetonitrile and formic acid 0.075% (75:25) at flow-rate 0.20 ml/min. SRM (selected reaction monitoring) mode was applied in order to ensure sufficient selectivity and sensitivity using the first most intensive transition as a quantitative (121>77 and 205>121) and second one for the confirmation purposes (121>93 and 205>109). The method was validated in terms of linearity (>0.9994), precision (0.5-3.8% RSD), accuracy (78.9-106.0%), LOD (limit of detection) and LOQ (limit of quantitation). The method can serve as an analytical tool for the detection and determination of quorum-sensing molecules in biological samples.

Hydroxytyrosol and tyrosol, the strong antioxidant present in large amount in virgin olive oil have been assayed by LC-MS/MS under MRM condition and isotope dilution method, using d(2)-labelled internal standards obtained by simple synthetic procedures. The assay has been performed under MRM condition monitoring two transitions for each analyte to improve the specificity. This paper deals with a modern approach for assaying the content of this polyphenols in virgin olive oil down to a limit of a few hundreds of parts per billion. Tyrosol and hydroxytyrosol ranged from 10 to 47ppm and from 5 to 25ppm in commercial olive oil, respectively. The accuracy (98-107%) and analytical parameters values confirm the reliability of the proposed approach. The method can be extended to any natural matrices, including mill wastes, after a simple step of sample preparation.

This work reports the survival (challenge tests) of foodborne pathogen species (Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, and Salmonella enterica) in Aloreña de Málaga table olive brines. The inhibitions were fit using a log-linear model with tail implemented in GInaFIT excel software. The olive brine had a considerable inhibitory effect on the pathogens. The residual (final) populations (Fp) after 24 h was below detection limit (<1.30 log10 cfu/mL) for all species assayed. The maximum death rate (kmax) was 9.98, 51.37, 38.35 and 53.01 h(-1), while the time for 4 log10 reductions (4Dr) was 0.96, 0.36, 0.36 and 0.24 h for E. coli, S. aureus, L. monocytogenes and S. enterica, respectively. Brine dilutions increased Fp and 4Dr, while decreased kmax. A cluster analysis showed that E. coli had an overall quite different behaviour being the most resistant species, but the others bacteria behaved similarly, especially S. aureus and S. enterica. Partial Least Squares regression showed that the most influential phenols on microbial survival were EDA (dialdehydic form of decarboxymethyl elenolic acid), HyEDA (EDA linked to hydroxytyrosol), hydroxytyrosol 4-glucoside, tyrosol, and oleoside 11-methyl ester. Results confirm the adverse habitats of table olives for foodborne pathogenic microorganisms.

In this article, we proposed very simple procedures to analyze important phenolic compounds in olive oil samples from different olive varieties. A nonaqueous CE method has been employed. The main phenolic alcohols in virgin olive oil (tyrosol and hydroxytyrosol) and some among the most abundant secoiridoid aglycone derivatives (dialdehydic form of decarboxymethyl elenoic acid linked to hydroxytyrosol, an isomer of oleuropein aglycone and the dialdehydic form of decarboxymethyl elenoic acid linked to tyrosol) were determined by a direct injection into the capillary of the olive oil dissolved in 1-propanol 1:1 v/v. For the determination of compounds present at lower concentrations, a very simple liquid-liquid extraction method with ethanol has been proposed. The extraction was performed using a relationship 5:1 w/v olive oil/ethanol to achieve the necessary preconcentration of the analytes and the ethanolic extracts were directly injected into the capillary to obtain a very important time reduction. Good recoveries were obtained with both the procedures, using an internal standard. Finally, these procedures were applied to the analysis of these compounds in extra virgin olive oil samples from different varieties of olive.

The concentration of different phenolic compounds was measured in Spanish Albariño and Portuguese Alvarinho and Loureiro white wines by capillary zone electrophoresis (CZE), in order to characterize them. Although all samples presented the same qualitative pattern (characterized by tyrosol; (-)-epicatechin; syringic acid; ferulic acid; p-coumaric acid; caffeic acid, gallic acid; 3,4-dihydroxybenzoic acid; cis-coumaroyl tartaric acid (COUTA); trans-COUTA; trans-caffeoyl tartaric acid (CAFTA), and hydroxycinnamic esters), some quantitative differences were observed. When samples were analyzed by high-performance liquid chromatography (HPLC), in order to compare the results obtained by both techniques, no significant qualitative or quantitative differences were obtained. Nevertheless, CZE proved to be a more convenient technique for the routinary analyses of these wines, due to better separation of the different compounds, better peak shapes, and higher speed than HPLC.

Phenolic compounds in Spanish virgin olive oil were analyzed by GC-MS after an SPE diol cartridge extraction and clean-up procedure. Posterior derivatization to trimethylsilyl (TMS) ethers using a mixture of hexamethyldisilazane:dimethylclorosilane (HMDS:DMCS) in pyridine (3:1:9) was performed. Several compounds were detected and 21 of them were identified. Free phenols such as hydroxytyrosol, tyrosol, tyrosyl and hydroxytyrosyl acetate, and aldehydic and dialdehydic forms of elenolic acid linked to tyrosol and hidroxytyrosol were the most abundant compounds. Likewise, oxidation products coming from the aldehydic and dialdehydic forms of elenolic acid, and of ligstroside and oleuropein aglycons, were detected, and their structure confirmed by other mass spectrometry technique, i.e., HPLC-APCI-MS. Individual oxidation products were isolated from an oxidized sample by preparative HPLC, converted to TMS ethers and re-analyzed by GC-MS. When necessary and for identification purposes, selective ion monitoring, namely, GC-MS-SIM, was employed. This is the first time that structures of oxidized forms are determined by GC-MS.

Artichoke is a relevant source of health-promoting compounds such as polyphenols and sesquiterpene lactones. In this study, the bioaccessibility and gut bioavailability of artichoke constituents were evaluated by combining in vitro digestion and large intestine fermentation, metabolomics, and Caco-2 human intestinal cells model. Moreover, the ability of artichoke polyphenols to modulate the in vitro starch digestibility was also explored. An untargeted metabolomic approach based on liquid chromatography quadrupole-time-of-flight (UHPLC/QTOF) mass spectrometry coupled with multivariate statistics was used to comprehensively screen the phytochemical composition of raw, digested, and fermented artichoke. Overall, a large abundance of phenolic acids and sesquiterpene lactones was detected, being 13.77 and 11.99 mg·g^-1, respectively. After 20 h of in vitro large intestine fermentation, a decrease in polyphenols and sesquiterpene lactones content was observed. The most abundant compounds characterizing the raw material (i.e., chlorogenic acid and cynaropicrin equivalents) showed an average % bioaccessibility of 1.6%. The highest % bioaccessibility values were recorded for flavonoids such as anthocyanin and flavone equivalents (on average, 13.6%). However, the relatively high bioavailability values recorded for flavonols, phenolic acids, and sesquiterpene lactones (from 71.6% up to 82.4%) demonstrated that these compounds are able to be transported through the Caco-2 monolayer. The phenolic compounds having the highest permeation rates through the Caco-2 model included low molecular weight phenolics such as tyrosol and 4-ethylcatechol; the isoflavonoids 3'-O-methylviolanone, equol 4'-O-glucuronide, and hydroxyisoflavone; together with the methyl and acetyl derivatives of glycosylated anthocyanins. Therefore, although human in vivo confirmatory trials are deemed possible, current findings provide insights into the mechanistic effects underlying artichoke polyphenols and sesquiterpenoids bioavailability following gastrointestinal and large intestine processes.