Search Results (9)

Background: The management of triple-negative breast cancer (TNBC) remains a therapeutic challenge due to the presence of multidrug resistance (MDR) and hypoxia-induced chemoresistance, both of which substantially reduce the efficacy of conventional chemotherapy. Although certain natural compounds have shown the ability to modulate these resistance mechanisms, their clinical application is hindered by poor solubility and limited bioavailability. Among such phenolic compounds, 7-hydroxytyrosol (HTyr)—a phenolic compound from olive oil and olive leaves—has been reported to modulate hypoxia-inducible factor-1 (HIF-1). Methods: In this study, we developed hyaluronic acid (HA)-decorated solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for the targeted and synergistic co-delivery of paclitaxel (PTX) and hydroxytyrosol carboxylic acid esters (C_n-HTyrCA), precursors that share the antioxidant biphenolic moiety with HTyr. Results: Among the formulations tested, SLNs of trilaurin (TL) exhibited the highest entrapment efficiency (EE%), optimal average particle size, Zeta potential, and good colloidal stability. Of the synthesized C_n-HTyrCA derivatives, C₈- and C₁₀-HTyrCA showed superior loading capacity. In vitro release profiles indicated a sustained drug release pattern for both nanoparticles. HA decoration led to a marked increase in particle size and induced a shift in surface charge, confirming successful decoration and suggesting enhanced targeting potential via HA-CD44 interaction. Cytotoxicity assays conducted on MDA-MB-231 cells showed that PTX-loaded TL-SLNs exerted enhanced antitumor activity, particularly when HA-decorated, and a synergistic effect was observed upon co-administration with SLNs loaded with C₈-HTyrCA. Conclusions: Overall, our findings support the potential of SLN as a promising strategy to overcome key resistance mechanisms in TNBC, enabling reduced chemotherapeutic dosing and improving therapeutic outcomes. Full article

One of the most persistent and damaging diseases in olive trees is olive knot disease. This disease is caused by an infection by the Gram-negative phytopathogenic bacterium Pseudomonas savastanoi pv. savastanoi that is notoriously difficult to control. The increasing demand for eco-friendly and sustainable agricultural solutions has driven research into plant-based agents. This study investigated the antibacterial properties of essential oils (EOs) and their constituents, olive mill wastewater (OMWW), the phenolic compound hydroxytyrosol (HTyr), and algae and garlic extracts, as well as copper-based and plant-stimulating commercial products against P. savastanoi pv. savastanoi, a significant olive tree pathogen. Antibacterial activity was determined using the Kirby–Bauer disc diffusion and broth microdilution methods. The EOs derived from Thymus vulgaris (thyme) and Origanum compactum (oregano), and their key components thymol and carvacrol, exhibited the strongest antibacterial efficacy. Conversely, the OMWW, plant-stimulating products, and algae and garlic extracts showed limited to no antibacterial activity in vitro, with their antibacterial properties determined using the disc diffusion method. While the EOs were highly effective in vitro, regardless of the testing method, their efficacy in bacterial growth inhibition was strain- and concentration-dependent, possibly highlighting some metabolic or genetic variability in the target pathogen, even though the MIC values against all tested strains of P. savastanoi pv. savastanoi were equal. Bacterial membrane disruption and the consequent leakage of metabolites were determined as the modes of action of carvacrol and oregano EO. Carvacrol also promoted plant growth in lettuce without significant phytotoxic effects, although minor necrotic lesions were observed in young olive leaves at higher concentrations, presenting these agents as potential next-generation green bactericides. Full article

This study explores approaches to enhancing the biostability of extra virgin olive oil (EVOO) supplemented with olive fruit extract (OFE) enriched with hydroxytyrosol (HTyr). The investigation focuses on prolonged deep frying (DF) conditions at 170 °C and 210 °C, over durations ranging from 3 to 48 h, with the aim of improving sensorial attributes, polyphenolic content, and thermal oxidative stability. Parameters, such as acidity, peroxide value (PV), K₂₃₂, K₂₇₀, ΔK, phenolic compounds, and sensory attributes, were monitored. The PV did not exceed the standard limit in HTyr-EVOO at 210 °C/24 h; however, in non-supplemented EVOOs, it remained within the limits only up to 210 °C/18 h. Acidity stayed within the acceptable limit (≤0.8) at 170 °C/24 h in both enriched and non-enriched EVOOs. K₂₃₂ values were ≤2.5 in HTyr-EVOO fried at 170 °C/18 h. K₂₇₀ and ΔK did not exceed the limits in HTyr-EVOO at 170 °C/3 h, whereas they surpassed them in non-supplemented oils. Additionally, HTyr and tyrosol levels were significantly higher (p < 0.05) in HTyr-EVOOs. Phenolic compounds, including verbascoside, pinoresinol, 1-acetoxypinoresinol, and phenolic acids, such as chlorogenic, vanillic, homovanillic, 4-dihydroxybenzoic, and caffeic acids, were detected in HTyr-EVOOs. Oxidized secoiridoid derivatives increased significantly as DF progressed. Moreover, sensory analysis revealed that positive attributes in EVOOs—such as fruity, bitter, and pungent notes—decreased significantly with increasing temperature and frying duration (p < 0.05). Beyond 210 °C/6 h, these attributes were rated at zero. However, HTyr-EVOOs exhibited lower rancidity compared to non-enriched oils under identical conditions, attributed to the protective effect of HTyr. In conclusion, HTyr-EVOOs demonstrated thermal stability up to 210 °C/6 h, retaining desirable sensory qualities, higher phenolic content, and reduced degradation. These findings indicate that natural OFEs have strong potential as food additive in deep fried EVOOs, enhancing sensory properties, health benefits, and overall oil stability. This innovation provides a practical solution for the food industry by improving the biostability and versatility of EVOO. Further research is recommended to investigate various EVOO categories and oils from diverse origins. Full article

Background/Objectives: Olive oil is valued for its health benefits, largely due to its bioactive compounds, including hydroxytyrosol (HTyr) and oleuropein (OLE), which have antioxidant, anti-inflammatory, and cardioprotective properties. However, many of these compounds are lost during the production process. This study developed a functional olive oil-derived product using water-in-oil emulsions (W/O) to incorporate commercial extracts rich in HTyr and OLE. Methods: HTyr and OLE were encapsulated in a W/O emulsion to preserve their bioactivity. The encapsulation efficiency (EE) was evaluated, and the performance of the emulsion was tested using an in vitro gastrointestinal digestion model. Bioaccessibility was measured by calculating the recovery percentage of HTyr and OLE during the digestion stages. Results: The results showed that OLE exhibited higher EE (88%) than HTyr (65%). During digestion, HTyr exhibited a gradual and controlled release, with bioaccessibility exceeding 80% in the gastric phase and a maintained stability throughout the intestinal phase. In contrast, OLE displayed high bioaccessibility in the gastric phase but experienced a notable decrease during the intestinal phase. Overall, the W/O emulsion provided superior protection and stability for both compounds, particularly for the secoiridoids, compared to the non-emulsified oil. Conclusions: The W/O emulsion improved the encapsulation and bioaccessibility of HTyr and OLE, constituting a promising method for enriching olive oil with bioactive phenolic compounds. Therefore, this method could enhance olive oil’s health benefits by increasing the availability of these bioactive compounds during digestion, offering the potential for the development of fortified foods. Full article

Silybin is a natural compound extensively studied for its hepatoprotective, neuroprotective and anticancer properties. Envisioning the enhancement of silybin potential by suitable modifications in its chemical structure, here, a series of new 7-O-alkyl silybins derivatives were synthesized by the Mitsunobu reaction starting from the silybins and tyrosol-based phenols, such as tyrosol (TYR, 3), 3-methoxytyrosol (MTYR, 4), and 3-hydroxytyrosol (HTYR, 5). This research sought to explore the antioxidant and anticancer properties of eighteen new derivatives and their mechanisms. In particular, the antioxidant properties of new derivatives outlined by the DPPH assay showed a very pronounced activity depending on the tyrosyl moiety (HTYR > MTYR >> TYR). A significant contribution of the HTYR moiety was observed for silybins and 2,3-dehydro-silybin-based derivatives. According to the very potent antioxidant activity, 2,3-dehydro-silybin derivatives 15ab, 15a, and 15b exerted the most potent anticancer activity in human prostate cancer PC-3 cells. Furthermore, flow cytometric analysis for cell cycle and apoptosis revealed that 15ab, 15a, and 15b induce strong G1 phase arrest and increase late apoptotic population in PC-3 cells. Additionally, Western blotting for apoptotic marker cleaved caspase-3 confirmed apoptosis induction by these silybin derivatives in PC-3 cells. These findings hold significant importance in the investigation of anticancer properties of silybin derivatives and strongly encourage swift investigation in pre-clinical models and clinical trials. Full article

The antitumor activity of polyphenols derived from extra virgin olive oil and, in particular the biological activity of HTyr, has been studied extensively. However, the use of HTyr as a therapeutic agent for clinical applications is limited by its low bioavailability and rapid excretion in humans. To overcome these limitations, several synthetic strategies have been optimized to prepare lipophenols and new compounds derived from HTyr to increase lipophilicity and bioavailability. One very promising ester is hydroxytyrosyl oleate (HTyr-OL) because the chemical structure of HTyr, which is responsible for several biological activities, is linked to the monounsaturated chain of oleic acid (OA), giving the compound high lipophilicity and thus bioavailability in the cellular environment. In this study, the in vitro cytotoxic, anti-proliferative, and apoptotic induction activities of HTyr-OL were evaluated against SH-SY5Y human neuroblastoma cells, and the effects were compared with those of HTyr and OA. The results showed that the biological activity of HTyr was maintained in HTyr-OL treatments at lower dosages. In addition, the shotgun proteomic approach was used to study HTyr-OL-treated and untreated neuroblastoma cells, revealing that the antioxidant, anti-proliferative and anti-inflammatory activities of HTyr-OL were observed in the unique proteins of the two groups of samples. Full article

Consumption of olive products has been established as a health-promoting dietary pattern due to their high content in compounds with eminent pharmacological properties and well-described bioactivities. However, their metabolism has not yet been fully described. The present critical review aimed to gather all scientific data of the past two decades regarding the absorption and metabolism of the foremost olive compounds, specifically of the phenylalcohols hydroxytyrosol (HTyr) and tyrosol (Tyr) and the secoiridoids oleacein (Olea), oleocanthal (Oleo) and oleuropein (Oleu). A meticulous record of the in vitro assays and in vivo (animals and humans) studies of the characteristic olive compounds was cited, and a critical discussion on their bioavailability and metabolism was performed taking into account data from their gut microbial metabolism. The existing critical review summarizes the existing knowledge regarding the bioavailability and metabolism of olive-characteristic phenylalchohols and secoiridoids and spotlights the lack of data for specific chemical groups and compounds. Critical observations and conclusions were derived from correlating structure with bioavailability data, while results from in vitro, animal and human studies were compared and discussed, giving significant insight to the future design of research approaches for the total bioavailability and metabolism exploration thereof. Full article

Extra virgin olive oil (EVOO) is one of the main ingredients of the Mediterranean diet. It is claimed as a functional food for its unique content of health-promoting compounds. Tyrosol (Tyr), Hydroxytyrosol (Htyr), and their phenolic derivatives present in EVOO show beneficial properties, and their identification and quantification, both in their free form and after the hydrolysis of more complex precursors, are important to certify its quality. An alternative method for quantifying free and total Tyr and Htyr in EVOO is presented using an LC–MS interface based on electron ionization (EI), called liquid electron ionization (LEI). This method requires neither sample preparation nor chromatography; the sample is diluted and injected. The selectivity and sensitivity were assessed in multiple reaction monitoring mode (MRM), obtaining confirmation and quantification in actual samples ranging from 5 to 11 mg/Kg for the free forms and from 32 to 80 mg/Kg for their total amount after hydrolysis. Two MS/MS transitions were acquired for both compounds using the Q/q ratios as confirmatory parameters. Standard addition calibration curves demonstrated optimal linearity and negligible matrix effects, allowing a correct quantification even without expensive and difficult to find labeled internal standards. After several weeks of operation, the system’s repeatability was excellent, with an intraday RSD (%) spanning from five to nine and an interday RSD (%) spanning from 9 to 11. Full article

This paper describes a circular economy process based on environmentally and economically sustainable procedures which was applied to the sector of olive oil processing on an industrial scale. Olea europaea L. tissues and by-products represent a renewable and low-cost source of polyphenols, in particular hydroxytyrosol (HTyr), a naturally occurring compound well known for its biological properties. Specifically, green leaves (GL), dried leaves (DL), and pitted olive pulp were treated with water in a pneumatic extractor to obtain the corresponding polyphenolic extracts. Three standardized fractions, named Soft Extract Olea GL, Soft Extract Olea DL, and Soft Extract Olea HTyr resulted after the following two steps: a separation process carried out by membrane technology, and a concentration step performed under reduced pressure and low temperature. The polyphenolic fractions showed antiradical activity and have potential industrial applications in the food, nutraceutical, pharmaceutical, feed, and agronomic fields. Novel functionalized extracts containing hydroxytyrosol methyl carbonate (HTyr-MC) were obtained from Soft Extract Olea HTyr through an innovative approach based on green chemistry procedures, which appear to be a promising tool to increase the applications of the polyphenolic extracts. Full article