Search Results (91)

Background/Objectives. Prostate cancer (PCa) is the second leading cause of cancer-related mortality among men in the United States. Treatment with second-generation androgen receptor (AR) inhibitors, such as enzalutamide, can trigger lineage plasticity, promoting the transdifferentiation of PCa cells into an AR-independent, poorly differentiated neuroendocrine phenotype (NEPC). The receptor tyrosine kinase EPHA3 is a critical driver for NEPC. It is overexpressed in PCa, particularly in androgen-independent and neuroendocrine subtypes. EPHA3 activates c-Myc signaling to enhance EZH2 expression, promoting histone H3K27 trimethylation. The neural transcription factor BRN2 functions upstream of both EZH2 and ASCL1. The latter regulates the Notch pathway ligand DLL3, thereby orchestrating neuroendocrine differentiation. Elevated expression of classical neuroendocrine markers CHGA and SYP is characteristic of the NEPC phenotype. This study reports the novel usage of the olive phenolic S-(-)-hydroxyoleocanthal (HOC, oleacein) to effectively control NEPC by targeting the EPHA3–BRN2–EZH2–ASCL1–DLL3–SYP–CHGA oncogenic network. Methods. Cell viability assays were conducted to assess in vitro effects. To model NEPC progression and recurrence, NCI-H660-Luc cells were xenografted into male athymic nude mice. RNA-sequencing was performed to compare the differentially expressed genes between placebo control and treated tumors. Results. HOC significantly attenuated the proliferation of NEPC NCI-H660 cells in vitro. Daily oral administration of HOC at 10 mg/kg body weight markedly suppressed the progression of NEPC NCI-H660-Luc tumors. Continued HOC treatments after surgical excision of the primary tumors substantially reduced locoregional recurrence. HOC significantly downregulated the expression of EPHA3, BRN2, EZH2, ASCL1, DLL3, SYP, and CHGA in treated primary and recurrence tumors versus placebo control. Conclusions. These findings establish HOC as a multifaceted therapeutic entity capable of disrupting key NEPC oncogenic networks, highlighting its potential as a novel lead intervention for aggressive NEPC. Full article

This research focuses on the additional valorization of olive leaves, a by-product of regular olive pruning, by increasing their secondary metabolite content through the combined application of biochar and a phenolic extract from olive leaves. A suspension of biochar, obtained by the pyrolysis of grapevine pruning residues, was prepared by mixing it in demineralized water (1.5 g; 5 L; 24 h). The phenolic extract was obtained by extracting lyophilized and ground olive leaves in demineralized water (50 g; 5 L; 24 h), while the combined preparation was obtained in an analogous manner (1.5 g biochar; 50 g olive leaf powder; 5 L water; 24 h). Treatments were applied at the beginning of July, 50 days after anthesis (May 16th) and included the following: (i) control treatment (demineralized water), (ii) biochar solution, (iii) phenolic extract solution, and (iv) a combined aqueous preparation of biochar and phenolic extract, all with the addition of a wetting agent. Trees of the olive cultivars Leccino and Istarska bjelica were sprayed with the corresponding preparation until runoff. Olive leaves were sampled three weeks after treatment (July 26th) and, after washing and drying, and were prepared for LC-MSMS analysis. Both biochar-based treatments induced the most potent effects, although responses differed between cultivars. In particular, apigenin derivatives, hydroxytyrosol, luteolin-7-rutinoside, and the secoiridoid oleacein showed apparent differences between biochar treatments and the control. Overall, higher concentrations of the sum of detected secoiridoids were observed in the leaf samples of ‘Istarska bjelica’ under BCH and BCH+PH treatments, whereas no such differences were found for ‘Leccino’ cultivar. Further research is needed to clarify the cultivar-dependent response of secondary metabolism in these olive cultivars and the mechanisms by which biochar foliar application modulates metabolite profiles. Full article

The bioactive properties of a phenolic extract (PE) obtained from olive mill vegetation water (OVW) in powder formulation were utilized to enrich a meat analog composed of lentils and champignon mushrooms. The primary phenolic compounds in this extract were oleacein, verbascoside, and hydroxytyrosol. The effects on the final product were assessed over eight days of storage at 4 °C ± 2 under 12 h of light. The control samples were compared with two meat analogs enriched with ascorbic acid (AA) at 5 g kg⁻¹ and one enriched with PE at 30 g kg⁻¹. The physicochemical parameters (pH, aw, color, texture, and total phenol content), antioxidant activity, microbial assessment, and sensory evaluations of meat analog samples were evaluated at three different time points (T0, T4, T8) during shelf life. The PE-enriched meat analogs maintained a relatively high and stable phenolic concentration throughout their shelf life, significantly enhancing the antioxidant activities of the final product. The addition of PE also influenced the growth of Enterococcus spp., Lactococcus spp., and Lactobacillus spp. during storage. The results of the triangular test indicated perceptible differences between AA and PE meat analogs. Meanwhile, the quantitative descriptive analysis (QDA) emphasized notable enhancements in odor and texture characteristics for PE-enriched samples. Plant-based meat analogs can benefit from the effective use of PE (antioxidant and sensory properties), supporting the sustainable reuse of olive oil by-products. Full article

Olive oil, a cornerstone of the Mediterranean diet, is increasingly recognized not only for its cardiovascular benefits but also for its potential role in cancer prevention and therapy. Among its bioactive constituents, several phenolic compounds—tyrosol, hydroxytyrosol, oleuropein, oleacein, and oleocanthal—have demonstrated promising anticancer activities in various experimental models. These compounds act synergistically through diverse mechanisms, including antioxidant, anti-inflammatory, and immunomodulatory effects, as well as modulation of cell proliferation, apoptosis, angiogenesis, and metastasis. Notably, oleocanthal selectively induces cancer cell death via lysosomal membrane permeabilization, while hydroxytyrosol and oleuropein exhibit potent radical-scavenging and anti-proliferative properties. This review synthesizes findings from in vitro, in vivo, and clinical studies on the anticancer potential of these polyphenols, with emphasis on their mechanisms of action and possible applications in cancer prevention and adjunctive therapy. Given the established link between obesity and cancer development, clinical studies examining the metabolic, anti-inflammatory, and immunomodulatory effects of olive polyphenols in populations with obesity or prediabetes provide valuable insights into their potential to influence cancer-related pathways indirectly. However, direct clinical evidence in cancer patients remains limited and preliminary, underscoring the need for focused, well-controlled trials with cancer-specific endpoints. Furthermore, it critically evaluates the translational relevance of these findings, highlighting gaps in clinical research and future directions. Literature was retrieved from Google Scholar, PubMed, and ScienceDirect using keywords such as cancer, immunomodulatory, anti-inflammatory, olive, tyrosol, hydroxytyrosol, oleuropein, oleacein, and oleocanthal. Given the rising global cancer burden and the favorable safety profiles of these natural molecules, elucidating their molecular actions may support the development of novel integrative therapeutic strategies. Full article

Olive oil, a cornerstone of the Mediterranean diet, contains a saponifiable lipid fraction rich in oleic acid, and a non-saponifiable fraction composed of minor bioactive constituents such as squalene, vitamin E, oleuropein aglycone, hydroxytyrosol, oleocanthal, and oleacein, among other phenolic and triterpenic compounds. These components are well-documented for their cardiovascular, anti-inflammatory, antioxidant, and neuroprotective activities. This review explores the physiological relevance of olive oil lipids and their derivatives on cellular membranes and ion transport systems, by combining biochemical and electrophysiological insights. We discuss how oleic acid and its metabolites influence membrane lipid composition, modulate fluidity, and reorganize lipid rafts—key elements for the proper localization and function of ion channels. Additionally, we examine evidence showing that several olive oil components regulate ion channels such as TRP, potassium, calcium, and chloride channels, as well as other transporters, thereby influencing ionic homeostasis, oxidative balance, and signal transduction in excitable and non-excitable cells. By combining these findings, we propose a conceptual framework in which olive oil lipids and their derivatives act as multimodal regulators of bioelectrical signaling. By modulating cell membrane dynamics, these functional molecules help maintain cellular communication and homeostasis. This integrative view not only strengthens our understanding of olive oil’s health-promoting effects but also opens new avenues for targeting ion-regulatory mechanisms in metabolic, cardiovascular, and neurological diseases. Full article

Background: Osteosarcopenic obesity (OSO) is an emerging syndrome characterized by the coexistence of obesity, sarcopenia, and osteoporosis, primarily affecting aging populations. Nutrition, especially polyphenol-rich foods like extra virgin olive oil (EVOO), may play a preventive or therapeutic role in OSO. This review aims to critically examine evidence from in vitro, in vivo, and human studies on the effects of olive oil polyphenols on OSO-related biological domains. Methods: This systematic review followed PRISMA guidelines. Studies were identified from PubMed and Google Scholar using MeSH terms related to olive oil, polyphenols, and OSO-associated conditions. In vitro and in vivo studies (both in animal and human models) published in the last ten years were included. The study protocol was registered with PROSPERO (CRD420251077836). Results: Fifteen studies were included: eight in vitro, four in vivo on animal models, and three human trials. Phenolic compounds such as hydroxytyrosol, oleuropein, oleocanthal, and oleacein demonstrated antioxidant, anti-inflammatory, anti-adipogenic, and osteo-/myo-protective effects. These compounds modulated key metabolic pathways and gene expression related to adipogenesis, bone metabolism, and muscle integrity. Conclusions: Olive oil polyphenols exhibit promising biological effects on the tissues involved in OSO. Although evidence is mostly preclinical, selected compounds (notably hydroxytyrosol and oleuropein) may serve as adjuncts in nutritional strategies for OSO prevention. Full article

The health benefits of extra virgin olive oil (EVOO), including improved cardiovascular health and metabolic function, are linked to its phenolic content. This study evaluated how storage duration and packaging affect the phenolic composition and sensory quality of Corbella EVOO. Oils were analyzed at production and after 6 and 12 months of storage in two types of packaging: bag-in-box; stainless steel containers with a nitrogen headspace. UPLC-MS/MS profiling quantified 23 phenolic compounds, predominantly secoiridoids such as oleuropein and ligstroside aglycones. Oleuropein aglycone increased over time, whereas ligstroside aglycone peaked mid-storage before declining, likely converting to oleocanthal. Lignans and flavonoids degraded during storage, although luteolin increased, potentially due to glucoside hydrolysis. Bag-in-box packaging better preserved phenolic content than stainless steel. A sensory analysis corroborated the chemical findings, with oils stored in stainless steel showing greater reductions in pungency and astringency. A Pearson correlation linked bitterness with oleuropein aglycone (r = 0.44) and oleacein (r = 0.66), pungency with oleocanthal (r = 0.81), and astringency with oleacein (r = 0.86) and oleocanthal (r = 0.71). These findings highlight the importance of packaging in preserving the phenolic composition responsible for the sensory qualities of EVOO over time. Full article

Storage conditions significantly impact the quality and functional properties of extra-virgin olive oil (EVOO). This study investigated the impact of light and dark storage on the nutritional quality of Umbrian EVOO and its effectiveness in tissue repair. The research aimed to simulate real-world conditions occurring during transport, retail, and domestic storage. Light exposure accelerated EVOO oxidation, significantly affecting peroxide levels (ranging from 5.19 to 24.30 meq O₂/kg of oil), total antioxidant capacity (measured spectrophotometrically, collectively ranging from 399.47 to 684.63 mg TE/kg of oil), and phenolic compound concentrations, particularly secoiridoids, lignans, and flavonoids (measured by HPLC, collectively ranging from 41.92 to 169.74 mg/kg of oil). Statistically significant differences (p < 0.01) were recorded between the control sample and the others in almost all cases, after storage. For instance, both light and dark exposure over a 24-month period resulted in a marked reduction (p < 0.01) in oleocanthal, pinoresinol, luteolin, and apigenin. Pigment levels were also affected, representing a rapid and cost-effective indicator of product oxidative degradation. The loss of phenolic compounds (especially oleacein and oleocanthal, which showed the most significant reductions of approximately 75% and 60%, respectively), impaired the EVOO’s wound-healing properties, affecting key tissue regeneration processes such as keratinocyte migration, hyaluronic acid synthesis, and angiogenesis. Notably, oleocanthal and oleacein, present at higher concentrations in fresh extracts, emerged as the primary contributors to the observed dermal effects and wound-healing processes, demonstrating a significant highest efficacy (p < 0.0001) in promoting wound closure. These findings underscore the critical role of EVOO storage in preserving its sensory properties and labile components with tissue repair and regeneration functions. Full article

Near-infrared (NIR) spectroscopy, combined with multivariate calibration techniques such as stepwise decorrelation of variables (SELECT) and ordinary least squares (OLS) regression, was used to develop robust, reduced-spectrum regression models for quantifying key phenolic compound markers in various olive oils. These oils included nine extra virgin olive oil (EVOO) varieties, refined olive oil (ROO) blended with virgin olive oil (VOO) or EVOO, and pomace olive oil, both with and without hydroxytyrosol (HTyr) supplementation. Olive oils were analyzed before and after deep frying. The results show that HTyr ranged from 7.28 mg/kg in Manzanilla (lowest) to 21.43 mg/kg in Royuela (highest). Tyrosol (Tyr) varied from 5.87 mg/kg in Royuela (lowest) to 14.86 mg/kg in Hojiblanca (highest). Similar trends were observed in all phenolic fractions across olive oil cultivars before and after deep-frying. HTyr supplementation significantly increased both HTyr and Tyr levels in non-fried and fried supplemented oils, with HTyr rising from single digits in some controls (around 0 mg/kg) to over 300 mg/kg in most of the supplemented samples. SELECT efficiently reduced redundancy by selecting the most vital wavelengths and thus significantly improved the regression models for key phenolic compounds, including HTyr, Tyr, caffeic acid, decarboxymethyl ligstroside aglycone in dialdehyde form (oleocanthal), decarboxymethyl oleuropein aglycone in dialdehyde form (oleacein), homovanillic acid, pinoresinol, oleuropein aglycone in oxidized aldehyde and hydroxylic form (OAOAH), ligstroside aglycone in oxidized aldehyde and hydroxylic form (LAOAH), and total phenolic content (TPC), achieving correlation coefficients (R) of 0.91–0.98. The SELECT-OLS method generated highly predictive models with minimal complexity, using at most 30 wavelengths out of 700. The number of decorrelated predictors varied, at 12, 14, 15, 30, 30, 21, 30, 30, 30, and 18 for HTyr, Tyr, caffeic acid, oleocanthal, oleacein, homovanillic acid, pinoresinol, OAOAH, LAOAH, and TPC, respectively, demonstrating the adaptability of the SELECT-OLS approach to different spectral patterns. These reliable calibration models enabled online and routine quantification of phenolic compounds in EVOO, VOO, ROO, including both non-fried and fried as well as supplemented and non-supplemented samples. They performed well across eight deep-frying conditions (3–6 h at 170–210 °C). Implementing an NIR instrument with optimized variable selection would simplify spectral analysis and reduce costs. The developed models all demonstrated strong predictive performance, with low leave-one-out mean prediction errors (LOOMPEs) with values of 15.69, 8.47, 3.64, 9.18, 16.71, 3.26, 8.57, 13.56, 56.36, and 82.38 mg/kg for HTyr, Tyr, caffeic acid, oleocanthal, oleacein, homovanillic acid, pinoresinol, OAOAH, LAOAH, and TPC, respectively. These results confirm that NIR spectroscopy combined with SELECT-OLS is a feasible, rapid, non-destructive, and eco-friendly tool for the reliable evaluation and quantification of phenolic content in edible oils. Full article

Climate crisis in the Mediterranean region has severely affected olive tree cultivation, especially due to the long, dry summers, when temperature often rises above 40 °C. In order to overcome such climate challenges in the olive sector, the particle film technology (PFT) was used, as an environmentally friendly alleviation technique, due mainly to the reflecting properties of clay materials. Three clay materials—attapulgite, talc, and kaolin—were applied foliarly to olive trees (both rainfed and irrigated) in July and August. At harvest, yield and oil production per tree were assessed, alongside olive oil quality and functional properties. Under irrigated conditions, trees treated with kaolin or talc in July exhibited the highest yields, whereas under rainfed conditions, trees treated with attapulgite in August, followed by those treated with talc in August, showed the greatest yields. Oil production exceeded that of controls in rainfed trees across nearly all clay treatments. Oils from irrigated trees treated with talc in August and rainfed trees treated with talc in July exhibited high phenolic content, though antioxidant capacity peaked in oils from trees treated with talc in August. These oils, along with those from trees treated with attapulgite in August, contained the highest concentrations of hydroxytyrosol and oleacein. In rainfed trees, most clay treatments resulted in oils with elevated oleic acid (C18:1) and reduced linoleic acid levels, yielding a high monounsaturated-to-polyunsaturated fatty acid ratio. In irrigated groves, August applications produced oils with distinct differences from controls, whereas in rainfed conditions, these differences were evident regardless of application timing. Clay materials offer a promising approach for mitigating abiotic stress under Mediterranean summer conditions; however, further research is needed to elucidate their mechanisms of action. This study represents the first report of foliar attapulgite application in plants and talc application in olive trees. Full article

Organoleptic features allow extra virgin olive oil (EVOO) to be distinguished from other commercial categories and to determine consumer preferences. In this study, we evaluated the influence of the phenolic content on the intensity of two characteristic attributes, namely, bitterness and pungency. The organoleptic analysis was carried out by a panel of trained tasters, who categorized a set of 200 EVOO samples produced in two consecutive crop seasons into three intensity levels (“Delicate”, “Medium”, and “Robust”) according to current regulations. The total phenolic content was correlated with the intensity of both attributes, but a different contribution was identified for individual phenols. For bitterness, aglycone isomers of oleuropein and ligstroside provided over 70% discrimination power (estimated by receiver operating characteristic analysis), while oleocanthal and oleacein were associated with a decrease in bitterness intensity. In addition, the intensity of pungency intensity was related to the content of oleocanthal, oleomissional, and oleokoronal, as they allowed the classification of about 75% of the “Robust” pungency EVOOs. With these premises, it is possible to obtain olive oils with the desired intensity of bitterness and pungency by controlling the factors that influence phenolic metabolism. Full article

This study investigated the impact of acidification on olive paste to enhance the extraction of olive oil enriched in bioactive phenolic compounds, aiming to develop a novel functional food. Recognizing that acidic pH promotes the activity of β-glucosidase responsible for oleuropein and ligstroside hydrolysis, food-grade organic acids—citric, ascorbic, and acetic acid—were added prior to malaxation to improve the bioactive compound content in the resulting oils. A randomized experimental design was employed, using three different doses of each acid (1, 2, and 4%) with three replicates per dose, alongside control trials without acid addition. Acidification did not affect olive oil extraction efficiency or alter quality parameters for extra virgin olive oils. Treatment with 1% ascorbic acid significantly increased phenolic compound content by 37% compared to controls. Secoiridoids comprised 79.4% of the total phenolic content, with oleacein as the predominant compound (237.58 ± 9.18 mg/kg), representing over 50% of the total. This increased oleacein concentration led to up to a 67% enhancement in antioxidant capacity (428.63 ± 31.57 mg Trolox/kg) compared to controls. The antioxidant capacities of 3,4-DHPEA, 3,4-DHPEA-EDA, and 3,4-DHPEA-EA were determined to be 12.05, 5.80, and 4.91 µmol TE/mg, respectively. Furthermore, the 1% ascorbic acid treatment enhanced volatile compounds associated with the lipoxygenase (LOX) pathway while reducing ethanol levels. Full article

Oleacein (Olea) and Oleocanthal (Oleo) are two phenolic compounds found in olive oil. Cell and animal studies have shown these two compounds can modulate inflammation, cancer, and neurodegenerative diseases. Unfortunately, the study of the pharmacokinetics of these two compounds appears difficult due to their high reactivity with primary amines. Indeed, the presence of primary amines in culture media and biological fluids raises the question as to whether the observed biological effects are attributable to the parent compounds or to their amine derivatives. In the present work, we investigated the adduct formation between Olea or Oleo and tris(hydroxymethyl)aminomethane (Tris), a well-known primary amine used primarily as a buffer system, showing that the reaction kinetics were extremely rapid. In addition, we assessed whether the newly formed Tris adducts, i.e., Olea-Tris and Oleo-Tris, retained their antioxidant capacity by means of the ABTS and DPPH radical scavenging assays, showing that their activity was partially maintained. Finally, we evaluated the anti-inflammatory activity of these adducts on murine BV-2 microglial cells stimulated with lipopolysaccharide (LPS) and kept in an amine-free culture medium, showing how the biological response varied as the compound was degraded. Taken together, these data demonstrate that the biological effects reported in the literature are mainly due to the amino-derivatives of Olea and Oleo rather than the polyphenols derived from their breakdown (tyrosol and hydroxytyrosol). Full article

Olive oil is widely recognized for its cancer-prevention properties, and its by-products, such as pomace and leaves, offer an opportunity for compound extraction. This study comprehensively reviews the antitumor activities of olive extracts and compounds in both in vitro and in vivo studies. Key compounds, including hydroxytyrosol (HT), oleuropein (OL), oleocanthal (OC), and maslinic acid (MA), demonstrated significant antiproliferative, apoptotic, antimigratory, and anti-invasive effects, along with selective cytotoxicity, particularly against breast and colorectal cancer. HT, OC, and MA showed anti-angiogenic effects, while HT and OC showed antimetastatic effects. Moreover, HT, OL, and OC also presented synergistic effects when combined with anticancer drugs, improving their efficacy. Additionally, HT, OL, and MA exhibited protective effects against several side effects of chemotherapy. These compounds are able to modulate important signaling pathways such as the mammalian target of rapamycin, regulate oxidative stress through reactive oxygen species production, modulate angiogenic factors, and induce autophagy. Interestingly, the synergistic effects of the compounds within olive extracts appear to be stronger than their individual action. There is a need for dose optimization, further mechanistic studies to clarify the precise mechanisms of action, and future studies using olive pomace extracts with animal models. Full article

Various protein-rich foods are traditionally immersed in virgin olive oil (VOO), a medium rich in phenols, which are health-promoting and sensorially important compounds. Immersing tofu in VOO may modify the sensory properties and nutritional value of both due to the oil’s hydrophilic phenol interactions with proteins and water. In this study, cubes of fresh tofu (T) (70% water) and freeze-dried tofu (FD-T) (5% water) were immersed in VOO for 7 days of cold storage. The changes in the phenolic compound content and standard quality parameters of the oil were noted after 1, 3, 5, and 7 days of contact with the tofu. The total phenols in the oil were determined using the Fast Blue BB assay, while single phenols were analyzed by HPLC-UV/VIS. During the 7 days, the total phenols in the oil decreased by up to 56% and 26% under the influence of fresh and freeze-dried tofu, respectively, including a significant decrease in hydroxytyrosol, oleacein, tyrosol, and oleocanthal. The water content and its release from fresh tofu significantly contributed to this decline. The degradation of the quality of the oil in contact with the fresh tofu was observed only in its sensory properties, with a marked reduction in the intensity of its fruitiness, bitterness and pungency. Full article