Olive Oil Industry By-Products as a Novel Source of Biophenols with a Promising Role in Alzheimer Disease Prevention.

This review explores the potential health benefits and applications of phenolic secoiridoids derived from olive oil by-products in the prevention of Alzheimer's disease (AD). As reviewed herein, polyphenols, such as epigallocatechin-3-gallate, epicatechin, and resveratrol, show in vitro and in vivo antioxidant, anti-inflammatory, and neuroprotective properties, and are particularly relevant in the context of AD, a leading cause of dementia globally. The olive oil industry, particularly in the Mediterranean region, produces significant amounts of waste, including leaves, pomace, and wastewater, which pose environmental challenges but also offer an untapped source of bioactive compounds. Despite promising in vitro and in vivo studies indicating that olive-derived polyphenols, such as oleuropein and hydroxytyrosol, may mitigate AD pathology, human clinical trials remain limited. The variability in extraction methods and the complex nature of AD further complicate research. Future studies should focus on standardizing the protocols and conducting robust clinical trials to fully assess the therapeutic potential of these compounds. This approach not only supports the development of new treatments for AD but also promotes environmental sustainability by valorizing olive oil industry waste.

Cholesteryl Phenolipids as Potential Biomembrane Antioxidants.

The lipophilization of polyphenols (phenolipids) may increase their affinity for membranes, leading to better antioxidant protection. Cholesteryl esters of caffeic, dihydrocaffeic, homoprotocatechuic and protocatechuic acids were synthetized in a one-step procedure with good to excellent yields of ~50-95%. After evaluation of their radical scavenging capacity by the DPPH method and establishing the anodic peak potential by cyclic voltammetry, their antioxidant capacity against AAPH-induced oxidative stress in soybean PC liposomes was determined. Their interaction with the liposomal membrane was studied with the aid of three fluorescence probes located at different depths in the membrane. The cholesteryl esters showed a better or similar radical scavenging capacity to that of α-tocopherol and a lower anodic peak potential than the corresponding parental phenolic acids. Cholesteryl esters were able to protect liposomes to a similar or greater extent than α-tocopherol. However, despite their antiradical capacity and being able to penetrate and orientate in the membrane in a parallel position to phospholipids, the antioxidant efficiency of cholesteryl esters was deeply dependent on the phenolipid polyphenolic moiety structure. When incorporated during liposome preparation, cholesteryl protocatechuate and caffeate showed more than double the activity of α-tocopherol. Thus, cholesteryl phenolipids may protect biomembranes against oxidative stress to a greater extent than α-tocopherol.

Anti-inflammatory effects of naringenin 8-sulphonate from Parinari excelsa Sabine stem bark and its semi-synthetic derivatives.

The inflammatory response is a vital mechanism for repairing damage induced by aberrant health states or external insults; however, persistent activation can be linked to numerous chronic diseases. The nuclear factor kappa ß (NF-κB) inflammatory pathway and its associated mediators have emerged as critical targets for therapeutic interventions aimed at modulating inflammation, necessitating ongoing drug development. Previous studies have reported the inhibitory effect of a hydroethanol extract derived from Parinari excelsa Sabine (Chrysobalanaceae) on tumour necrosis factor-alpha (TNF-α), but the phytoconstituents and mechanisms of action remained elusive. The primary objective of this study was to elucidate the phytochemical composition of P. excelsa stem bark and its role in the mechanisms underpinning its biological activity. Two compounds were detected via HPLC-DAD-ESI(Ion Trap)-MS2 analysis. The predominant compound was isolated and identified as naringenin-8-sulphonate (1), while the identity of the second compound (compound 2) could not be determined. Both compound 1 and the extract were assessed for anti-inflammatory properties using a cell-based inflammation model, in which THP-1-derived macrophages were stimulated with LPS to examine the treatments' effects on various stages of the NF-κB pathway. Compound 1, whose biological activity is reported here for the first time, demonstrated inhibition of NF-κB activity, reduction in interleukin 6 (IL-6), TNF-α, and interleukin 1 beta (IL-1ß) production, as well as a decrease in p65 nuclear translocation in THP-1 cells, thus highlighting the potential role of sulphur substituents in the activity of naringenin (3). To explore the influence of sulphation on the anti-inflammatory properties of naringenin derivatives, we synthesized naringenin-4'-O-sulphate (4) and naringenin-7-O-sulphate (5) and evaluated their anti-inflammatory effects. Naringenin derivatives 4 and 5 did not display potent anti-inflammatory activities; however, compound 4 reduced IL-1ß production, and compound 5 diminished p65 translocation, with both exhibiting the capacity to inhibit TNF-α and IL-6 production. Collectively, the findings demonstrated that the P. excelsa extract was more efficacious than all tested compounds, while providing insights into the role of sulphation in the anti-inflammatory activity of naringenin derivatives.

A biochemical perspective on the fate of virgin olive oil phenolic compounds in vivo.

The chemistry of the phenolic compounds found in virgin olive oil (VOO) is very complex due, not only to the different classes of polyphenols that can be found in it, but, above all, due to the existence of a very specific phenol class found only in oleaceae plants: the secoiridoids. Searching in the Scopus data base the keywords flavonoid, phenolic acid, lignin and secoiridoid, we can find a number of 148174, 79435, 11326 and 1392 research articles respectively, showing how little is devote to the latter class of compounds. Moreover, in contrast with other classes, that include only phenolic compounds, secoiridoids may include phenolic and non-phenolic compounds, being the articles concerning phenolic secoiridoids much less than the half of the abovementioned articles. Therefore, it is important to clarify the structures of these compounds and their chemistry, as this knowledge will help understand their bioactivity and metabolism studies, usually performed by researchers with a more health science's related background. In this review, all the structures found in many research articles concerning VOO phenolic compounds chemistry and metabolism was gathered, with a special attention devoted to the secoiridoids, the main phenolic compound class found in olives, VOO and olive leaf.

Unexpected Antioxidant Efficiency of Chlorogenic Acid Phenolipids in Fish Oil-in-Water Nanoemulsions: An Example of How Relatively Low Interfacial Concentrations Can Make Antioxidants to Be Inefficient.

Selecting effective antioxidants is challenging since their efficiency in inhibiting lipid oxidation depends on the rate constants of the chemical reactions involved and their concentration at the reaction site, i.e., at the interfacial region. Accumulation of antioxidants at the interface of emulsions is key to modulate their efficiency in inhibiting lipid oxidation but its control was not well understood, especially in emulsions. It can be optimized by modifying the physicochemical properties of antioxidants or the environmental conditions. In this work, we analyze the effects of surfactant concentration, droplet size, and oil to water ratio on the effective interfacial concentration of a set of chlorogenic acid (CGA) esters in fish oil-in-water (O/W) emulsions and nanoemulsions and on their antioxidant efficiency. A well-established pseudophase kinetic model is used to determine in the intact emulsified systems the effective concentrations of the antioxidants (AOs). The relative oxidative stability of the emulsions is assessed by monitoring the formation of primary oxidation products with time. Results show that the concentration of all AOs at the interfacial region is much higher (20-90 fold) than the stoichiometric one but is much lower than those of other phenolipid series such as caffeic or hydroxytyrosol derivatives. The main parameter controlling the interfacial concentration of antioxidants is the surfactant volume fraction, ΦI, followed by the O/W ratio. Changes in the droplet sizes (emulsions and nanoemulsions) have no influence on the interfacial concentrations. Despite the high radical scavenging capacity of CGA derivatives and their being concentrated at the interfacial region, the investigated AOs do not show a significant effect in inhibiting lipid oxidation in contrast with what is observed using other series of homologous antioxidants with similar reactivity. Results are tentatively interpreted in terms of the relatively low interfacial concentrations of the antioxidants, which may not be high enough to make the rate of the inhibition reaction faster than the rate of radical propagation.

Modeling Chemical Reactivity at the Interfaces of Emulsions: Effects of Partitioning and Temperature.

Bulk phase chemistry is hardly ever a reasonable approximation to interpret chemical reactivity in compartmentalized systems, because multiphasic systems may alter the course of chemical reactions by modifying the local concentrations and orientations of reactants and by modifying their physical properties (acid-base equilibria, redox potentials, etc.), making them-or inducing them-to react in a selective manner. Exploiting multiphasic systems as beneficial reaction media requires an understanding of their effects on chemical reactivity. Chemical reactions in multiphasic systems follow the same laws as in bulk solution, and the measured or observed rate constant of bimolecular reactions can be expressed, under dynamic equilibrium conditions, in terms of the product of the rate constant and of the concentrations of reactants. In emulsions, reactants distribute between the oil, water, and interfacial regions according to their polarity. However, determining the distributions of reactive components in intact emulsions is arduous because it is physically impossible to separate the interfacial region from the oil and aqueous ones without disrupting the existing equilibria and, therefore, need to be determined in the intact emulsions. The challenge is, thus, to develop models to correctly interpret chemical reactivity. Here, we will review the application of the pseudophase kinetic model to emulsions, which allows us to model chemical reactivity under a variety of experimental conditions and, by carrying out an appropriate kinetic analysis, will provide important kineticparameters.

Effects of Surfactant Volume Fraction on the Antioxidant Efficiency and on The Interfacial Concentrations of Octyl and Tetradecyl p-Coumarates in Corn Oil-in-Water Emulsions.

Surfactants have been used for decades in the food industry for the preparation of lipid-based emulsified food stuffs. They play two main roles in the emulsification processes: first they decrease the interfacial tension between the oil and water, facilitating droplet deformation and rupture; second, they reduce droplet coalescence by forming steric barriers. However, addition of surfactants to binary oil-water mixtures also brings up the formation of three-dimensional interfacial layers, surrounding each emulsion droplet, that significantly alter chemical reactivity. This is the case, for instance, in the inhibition reaction between antioxidants and the lipid radicals formed in the course of the spontaneous oxidation reaction of unsaturated lipids, which are commonly employed in the preparation of food-grade emulsions. The rate of the inhibition reaction depends on the effective concentrations of antioxidants, which are mostly controlled by the amount of surfactant employed in the preparation of the emulsion. In this work, we analyze the effects of the surfactant Tween 20 on the oxidative stability and on the effective concentrations of two model antioxidants derived from cinnamic acid, determining their interfacial concentrations in the intact emulsions to avoid disrupting the existing equilibria and biasing results. For this purpose, a recently developed methodology was employed, and experimental results were interpreted on the grounds of a pseudophase kinetic model.

An efficient one-pot synthesis of polyphenolic amino acids and evaluation of their radical-scavenging activity.

A simple and efficient procedure for the synthesis of N-acyl 4-hydroxy, 4-hydroxy-3-methoxy and 3,4-dihydroxy phenylglycine amides by a strategy based on the multicomponent Ugi reaction is proposed. Hydroxybenzaldehyde derivatives were reacted with 4-methoxybenzylamine, cyclohexyl isocyanide and benzoic acid or 2-naphthylacetic acid to give Ugi adducts that were treated with trifluoroacetic acid yielding N-acyl hydroxyphenylglycine amides in good yields. The same procedure using as acid component protocatechuic acid or hydrocaffeic acid gave N-catechoyl 3,4-dihydroxyphenylglycine amides. The use of N-benzyloxycarbonylglycine as acid component allowed the preparation of a 3,4-dihydroxyphenylglycyl dipeptide derivative. Radical-scavenging activity studies of the polyphenolic amino acid derivatives showed a sharp increase in activity with the increase in number of hydroxyl or catechol groups present. Cyclic voltammetry experiments established a correlation between oxidation peak potentials and the radical-scavenging activity.

Control of antioxidant efficiency of chlorogenates in emulsions: modulation of antioxidant interfacial concentrations.

BACKGROUND: Controlling the interfacial concentrations of antioxidants (AOs) in oil-in-water emulsions can be regarded as a unique approach for increasing the efficiency of AOs in inhibiting the oxidation of lipids. Classical methods to determine the AO distribution in binary systems cannot be employed and their distribution needs to be assessed in the intact emulsion. RESULTS: We have employed a well-established kinetic method to determine the distribution of a homologous series of AOs derived of chlorogenic acid in olive oil-in-water emulsions and analyse the effects of AO hydrophobicity on their distributions and their efficiencies. Results indicate that variations in the efficiency of chlorogenates in emulsions are due to differences in their interfacial concentrations. Their interfacial concentrations AOI were much higher (20- to 150-fold) than their stoichiometric concentrations. On the other hand, their concentrations in the oil region were 1.5- to 0.1-fold. Results also show the complex effect of the oil-to-water ratio employed in the preparation of the emulsions on the (AOI ) values. CONCLUSION: Results highlight the key role of the interfacial region and of its composition (interfacial AO molarity, emulsifier concentration, oil-to-water ratio) in interpreting the efficiency of AOs in inhibiting lipid oxidation in emulsions. Thus, a careful modulation of these parameters is necessary to ensure optimum AO efficiency. © 2019 Society of Chemical Industry.

In Vitro Anti-Inflammatory and Cytotoxic Effects of Aqueous Extracts from the Edible Sea Anemones Anemonia sulcata and Actinia equina.

Marine invertebrates have been attracting the attention of researchers for their application in nutrition, agriculture, and the pharmaceutical industry, among others. Concerning sea anemones (Cnidaria), little is known regarding their metabolic profiles and potential value as a source of pharmacologically-active agents. In this work, the chemical profiles of two species of sea anemones Actinia equina and Anemonia sulcata, were studied by high-performance liquid chromatography with diode-array detection (HPLC-DAD) and its impact upon immune and gastric cells was evaluated. In both species, the methylpyridinium alkaloid homarine was the major compound in aqueous extracts. The extracts were effective in reducing lipopolysaccharide (LPS)-induced levels of nitric oxide (NO) and intracellular reactive oxygen species (ROS) in a macrophage model of inflammation. Both the extracts and the alkaloid homarine were effective in inhibiting phospholipase A2 (PLA2), a pivotal enzyme in the initial steps of the inflammatory cascade. In order to mimic the oral consumption of these extracts; their effect upon human gastric cells was evaluated. While no caspase-9 activation was detected, the fact that the endoplasmic reticulum-resident caspase-4, and also caspase-3, were activated points to a non-classical mechanism of apoptosis in human gastric cells. This work provides new insights on the toxicity and biological potential of sea anemones increasingly present in human nutrition.

Physical evidence that the variations in the efficiency of homologous series of antioxidants in emulsions are a result of differences in their distribution.

BACKGROUND: The relationships between the hydrophilic-lipophilic balance (HLB) of antioxidants (AOs) and their distributions and efficiencies in emulsions are not fully understood. Recent reports indicate that, for series of homologous antioxidants of different hydrophobicity, the variation of their efficiency with the HLB of the AO increases with the alkyl chain length up to a maximum (C3 -C8 ester) followed by a decrease (cut-off effect). RESULTS: We determined the distributions of a series of caffeic acid derivatives in intact soybean emulsions by employing a specifically designed chemical probe located in the interfacial region of the emulsion. We also determined the AO efficiencies in the very same emulsions. We demonstrate that the variation of the percentage of AO in the interfacial region of soybean oil-in-water emulsions with the AO HLB parallels that of their antioxidant efficiency. CONCLUSION: The results provide physical evidence that the variations in the efficiency of homologous series of antioxidants in emulsions are the result of differences in their distribution. The results confirm that, with other things being equal, there is a direct relationship between the percentage of AO in the interfacial region of the emulsions and their efficiency, providing a natural explanation, based on molecular properties, of the cut-off effect. © 2016 Society of Chemical Industry.

Effects of the dietary incorporation of olive leaves on growth performance, digestibility, blood parameters and meat quality of growing pigs.

BACKGROUND: In a preliminary study the oxidative stability and tocopherol content of pork meat were shown to be improved by olive leaf (OL) feed supplementation at 50 and 100 g kg(-1) . However, growth performance was affected negatively. Therefore the objective of the present study was to assess the influence of OL supplementation at a lower level on feed digestibility, growth performance and meat quality. RESULTS: Pigs were fed a basal diet (control), a basal diet with 25 g OL kg(-1) (OL2.5) or a basal diet with 50 g OL kg(-1) (OL5). The incorporation of OL significantly decreased growth rates (P = 0.010) and backfat thickness (P = 0.035) and increased feed/gain ratio (P = 0.032) in the OL5 group. Feed/gain ratio increased more for females (P = 0.001). The incorporation of OL decreased the crude fat (P = 0.006) and protein (P = 0.037) digestibility of both OL diets. Nevertheless, OL was effective in increasing the tocopherol content of meat (P = 0.009). However, meat from pigs fed the OL diets showed similar conjugated diene content, pH and colour parameters to that from pigs fed the control diet, even after 6 days of storage at 4 °C. CONCLUSION: The data indicate that olive leaves may be included in pig diets at 25 g kg(-1) in order to improve the tocopherol content of meat without excessively compromising growth performance.

Analysis of the Efficiency of Antioxidants in Inhibiting Lipid Oxidation in Terms of Characteristic Kinetic Parameters.

In this work, we aim to find physical evidence demonstrating the crucial role that the effective concentration of antioxidants (AOs) present at the interfacial region of emulsions has in controlling the inhibition of the lipid oxidation reaction. We prepared a series of antioxidants of different hydrophobicities derived from chlorogenic and protocatechuic acids. We first monitored, in intact emulsions, the (sigmoidal) production of conjugated dienes and determined the corresponding induction times, tind. Independently, we determined the effective concentrations of the antioxidants in the same intact emulsions. Results show that both the length of the induction periods and the antioxidant interfacial concentrations parallel each other, with a maximum at the octyl-dodecyl derivatives. The ratio between the interfacial antioxidant concentrations and the induction periods remains constant for all AOs in the same series, so that the rates of initiation of lipid oxidation are the same regardless of the hydrophobicity of the antioxidant employed. The constancy in the rate of initiation provides strong experimental evidence for a direct relationship between interfacial concentrations and antioxidant efficiencies. Results suggest new possibilities to investigate lipid peroxidation under non-forced conditions and are of interest to formulators interested in preparing emulsions with antimicrobial properties.

In silico and in vitro chemometrics, cell toxicity and permeability of naringenin 8-sulphonate and derivatives.

Background: Sulphur containing natural compounds are among the most biologically relevant metabolites in vivo. Naringenin 8-sulphonate from Parinari excelsa Sabine was evaluated in a previous work, demonstrating ability to act as a natural anti-inflammatory. Although the interference of this molecule against different inflammatory mediators was described, there is no information regarding its potential toxicity and pharmacokinetics, which are essential for its capacity to reach its therapeutic targets. In fact, despite the existence of reports on naringenin ADMET properties, the influence of sulphation patterns on them remains unknown. Objectives: This work aims to assess the in vitro pharmacokinetic and toxicological behavior of naringenin 8-sulphonate, as well as to understand the importance of the presence and position of the sulphur containing group for that. Methods: Naringenin 8-sulphonate physicochemical and ADMET properties were investigated using in silico tools and cell-based in vitro models. At the same time, naringenin and naringenin 4'-O-sulphate were investigated to evaluate the impact of the sulphonate group on the results. ADMETlab 2.0 in silico tool was used to predict the compounds' physicochemical descriptors. Pharmacokinetic properties were determined experimentally in vitro. While MRC-5 lung fibroblasts and HaCaT keratinocytes were used to evaluate the cytotoxicity of samples through MTT and LDH assays, Caco-2 human intestinal epithelial cells were used for the determination of genotoxicity, through alkaline comet assay, and as a permeability model to assess the ability of compounds to cross biological barriers. Results: Experimental determinations showed that none of the compounds was cytotoxic. In terms of genotoxicity, naringenin 8-sulphonate and naringenin caused significant DNA fragmentation, whereas naringenin 4'-O-sulphate did not. When it comes to permeability, the two sulphur-containing compounds with a sulphur containing group were clearly less capable to cross the Caco-2 cell barrier than naringenin. Conclusion: In this study, we conclude that the sulphur containing group from naringenin 8-sulphonate is disadvantageous for the molecule in terms of ADMET properties, being particularly impactful in the permeability in intestinal barrier models. Thus, this work provides important insights regarding the role of flavonoids sulphation and sulphonation upon pharmacokinetics and toxicity.

A simple method for the determination of bioactive antioxidants in virgin olive oils.

BACKGROUND: The importance of olive polyphenols as bioactive compounds has grown in recent years as a result of intensive research on their anticancer, antiatherosclerotic and antihypertensive activities. However, there is currently no official method for determining the content of polyphenols in olive oils because of the technical difficulties in their determination. Here a simple method for the analysis of extra virgin olive oil o-diphenols by visible spectrometry is proposed and compared with the traditional method of solid phase extraction followed by colorimetric determination using sodium molybdate or Folin-Ciocalteu reagent or by high-performance liquid chromatography (HPLC) analysis using UV detection. This new approach to determining total o-diphenolic compounds exploits the oxidation of o-diphenols to quinones in a basic medium. RESULTS: Preliminary results showed a better correlation between the total o-diphenol determination by HPLC and by the proposed method (R(2) = 0.9229) than between the total o-diphenol determination by HPLC and by the molybdate colorimetric method (R(2) = 0.8689). A good correlation was also observed between the total phenolic content determined by HPLC and by the proposed method (R(2) = 0.8196), but this correlation was a little lower than the one obtained between the HPLC method and the Folin-Ciocalteu method (R(2) = 0.8752). CONCLUSION: The proposed method involves very little sample manipulation, requires inexpensive reagents and can be performed in less than 40 min for several samples at the same time, using olive oil samples of only 1-2 g.

Partitioning of Antioxidants in Edible Oil-Water Binary Systems and in Oil-in-Water Emulsions.

In recent years, partitioning of antioxidants in oil-water two-phase systems has received great interest because of their potential in the downstream processing of biomolecules, their benefits in health, and because partition constant values between water and model organic solvents are closely related to important biological and pharmaceutical properties such as bioavailability, passive transport, membrane permeability, and metabolism. Partitioning is also of general interest in the oil industry. Edible oils such as olive oil contain a variety of bioactive components that, depending on their partition constants, end up in an aqueous phase when extracted from olive fruits. Frequently, waste waters are subsequently discarded, but their recovery would allow for obtaining extracts with antioxidant and/or biological activities, adding commercial value to the wastes and, at the same time, would allow for minimizing environmental risks. Thus, given the importance of partitioning antioxidants, in this manuscript, we review the background theory necessary to derive the relevant equations necessary to describe, quantitatively, the partitioning of antioxidants (and, in general, other drugs) and the common methods for determining their partition constants in both binary (PWOIL) and multiphasic systems composed with edible oils. We also include some discussion on the usefulness (or not) of extrapolating the widely employed octanol-water partition constant (PWOCT) values to predict PWOIL values as well as on the effects of acidity and temperature on their distributions. Finally, there is a brief section discussing the importance of partitioning in lipidic oil-in-water emulsions, where two partition constants, that between the oil-interfacial, POI, and that between aqueous-interfacial, PwI, regions, which are needed to describe the partitioning of antioxidants, and whose values cannot be predicted from the PWOIL or the PWOCT ones.

Olive oil oleogels as strategy to confer nutritional advantages to burgers.

The effect of bovine back fat replacement by oleogels containing pork skin and olive oil on the oxidative stability, physicochemical, technological, nutritional, and sensory parameters of burgers was evaluated. Four different hamburger (H) were manufactured: with 90 % of lean beef and 10 % of bovine back fat (control, HC), or with 10 % of pork skin/water/virgin olive oil (HVOO), stripped olive oil added of an olive leaf extract (HESOO) or stripped olive oil (HSOO) oleogels, at 20:60:20 ratio. Physical-chemical stability was assessed after storage for 7 days at 4 °C and for 90 days at -20 °C, under non-vacuum and vacuum packaging. A reduction in the fat content by 80 % and in the energy content by 35 %, an increase in the protein content by 15 % and a better fatty acid profile were achieved in the oleogel containing burgers. After processing at 180 °C (grill), hardness, chewiness, sensory parameters and overall acceptability were high and comparable to control. All burgers were oxidative stable during 7 days at 4 °C. After storage for 90 days at -20 °C, only HSOO samples stored under non-vacuum packaging were oxidized. The antioxidant content in samples HVOO and HESOO efficiently prevented the oxidation of these samples.

Anti-Inflammatory Activity of Olive Oil Polyphenols-The Role of Oleacein and Its Metabolites.

The anti-inflammatory potential of oleacein, the main polyphenolic compound found in olive oil, and its main metabolites were characterized by their effects on RAW 264.7 macrophages challenged with lipopolysaccharide (LPS), and by their ability to inhibit enzymes of the arachidonic acid metabolism with a key role in the synthesis of pro-inflammatory lipid mediators. Oleacein at 12.5 µM significantly decreased the amount of L-citrulline and ●NO generated by LPS-stimulated macrophages. Hydroxytyrosol, hydroxytyrosol acetate and hydroxytyrosol acetate sulfate were also able to reduce the cellular amount of ●NO, although to a lesser extent. In contrast, hydroxytyrosol glucuronide and sulfate did not show detectable effects. Oleacein was also able to inhibit the coupled PLA2 + 5-LOX enzyme system (IC50 = 16.11 µM), as well as the 5-LOX enzyme (IC50 = 45.02 µM). Although with lower activity, both hydroxytyrosol and hydroxytyrosol acetate were also capable of inhibiting these enzymes at a concentration of 100 µM. None of the other tested metabolites showed a capacity to inhibit these enzymes. In contrast, all compounds, including glucuronides and sulfate metabolites, showed a remarkable capacity to inhibit both cyclooxygenase isoforms, COX-1 and COX-2, with IC50 values lower than 3 µM. Therefore, oleacein and its metabolites have the ability to modulate ●NO- and arachidonic acid-dependent inflammatory cascades, contributing to the anti-inflammatory activity associated with olive oil polyphenols.

Biochemistry of Antioxidants: Mechanisms and Pharmaceutical Applications.

Natural antioxidants from fruits and vegetables, meats, eggs and fish protect cells from the damage caused by free radicals. They are widely used to reduce food loss and waste, minimizing lipid oxidation, as well as for their effects on health through pharmaceutical preparations. In fact, the use of natural antioxidants is among the main efforts made to relieve the pressure on natural resources and to move towards more sustainable food and pharmaceutical systems. Alternative food waste management approaches include the valorization of by-products as a source of phenolic compounds for functional food formulations. In this review, we will deal with the chemistry of antioxidants, including their molecular structures and reaction mechanisms. The biochemical aspects will also be reviewed, including the effects of acidity and temperature on their partitioning in binary and multiphasic systems. The poor bioavailability of antioxidants remains a huge constraint for clinical applications, and we will briefly describe some delivery systems that provide for enhanced pharmacological action of antioxidants via drug targeting and increased bioavailability. The pharmacological activity of antioxidants can be improved by designing nanotechnology-based formulations, and recent nanoformulations include nanoparticles, polymeric micelles, liposomes/proliposomes, phytosomes and solid lipid nanoparticles, all showing promising outcomes in improving the efficiency and bioavailability of antioxidants. Finally, an overview of the pharmacological effects, therapeutic properties and future choice of antioxidants will be incorporated.

Distributions of α- and δ-TOCopherol in Intact Olive and Soybean Oil-in-Water Emulsions at Various Acidities: A Test of the Sensitivity of the Pseudophase Kinetic Model.

During the last years, the formalism of the pseudophase kinetic model (PKM) has been successfully applied to determine the distributions of antioxidants and their effective interfacial concentrations, and to assess the relative importance of emulsion and antioxidant properties (oil and surfactant nature, temperature, acidity, chemical structure, hydrophilic-liphophilic balance (HLB), etc.) on their efficiency in intact lipid-based emulsions. The PKM permits separating the contributions of the medium and of the concentration to the overall rate of the reaction. In this paper, we report the results of a specifically designed experiment to further test the suitability of the PKM to evaluate the distributions of antioxidants among the various regions of intact lipid-based emulsions and provide insights into their chemical reactivity in multiphasic systems. For this purpose, we employed the antioxidants α- and δ-TOCopherol (α- and δ-TOC, respectively) and determined, at different acidities well below their pKa, the interfacial rate constants kI for the reaction between 16-ArN2+ and α- and δ-TOC, and the antioxidant distributions in intact emulsions prepared with olive and soybean oils. Results show that the effective interfacial concentration of δ-TOC is higher than that of α-TOC in 1:9 (v/v) soybean and 1:9 olive oil emulsions. The effective interfacial concentrations of tocopherols are much higher (15-96-fold) than the stoichiometric concentrations, as the effective interfacial concentrations of both δ-TOC and α-TOC in soybean oil emulsions are higher (2-fold) than those in olive oil emulsions. Overall, the results demonstrate that the PKM grants an effective separation of the medium and concentration effects, demonstrating that the PKM constitutes a powerful non-destructive tool to determine antioxidant concentrations in intact emulsions and to assess the effects of various factors affecting them.