Mitigation of biochemical alterations in streptozotocin-induced gestational diabetes in rats through mesenchymal stem cells and olive leaf extract.

Treatment with mesenchymal stem cells (MSCs) is a new promising therapeutic approach with substantial very auspicious potential. They have been shown to protect various played a role in protecting organs from damage. This current study aims to evaluate the impact of the treatment of olive leaf extract (OLE), bone marrow-derived (BM-MSCs), and their combination on hepatotoxicity in pregnant rats with diabetes. METHODS: Animals were divided into five groups (10 pregnant rats each) as follows: control, GDM group, and OLE group (rats received streptozotocin (STZ) at a dose of 35 mg/kg body weight). GD + OLE set (pregnant rats were administered OLE at a dose of 200 mg extract/kg of body weight). GD + MSCs group (pregnant rats treated with MSCs). GD + OLE + MSCs group (pregnant rats were treated with both MSCs and OLE). RESULTS: STZ induced significant changes in liver parameters, lipid profile, and oxidative stress. Treatment with OLE, BM-MSCs, and their combination significantly ameliorated STZ-induced liver damage and oxidative stress. STZ resulted in a significant change in liver parameters, lipid profile, and oxidative stress. OLE, BM-MSC, and combination have significantly improved STZ-induced deterioration in liver and improved oxidative stress. CONCLUSIONS: The findings demonstrate that OLE and BM-MSCs have beneficial effects in mitigating diabetes-related liver alterations. These outcomes showed that OLE and BM-MSC have beneficial effects in alleviating diabetes-related alterations in the liver.

Antimicrobial Activity of Olive Leaf Extract to Oral Candida Isolates.

OBJECTIVES: The aim of this study was to determine the antifungal activity of olive leaf extract (OLE) and the synergistic effect of standard antifungal therapy and OLE against clinical oral Candida species' isolates. MATERIALS AND METHOD: The susceptibility of 60 clinical isolates of the Candida species (36 C. albicans, 16 C. krusei, 5 C. glabrata and 3 C. tropicalis) was tested with four concentrations of OLE (60 µg/µL, 120 µg/µL, 240 µg/µL and 333 µg/µL) and the synergistic effect of standard antifungal therapy and OLE (miconazole (MIC) + 333 µg/µL OLE and nystatin (NYS) + 333 µg/µL OLE). The antimicrobial activity was tested using the disk diffusion method. RESULTS: All concentrations (60 µg/µL, 120 µg/µL, 240 µg/µL and 333 µg/µL) of OLE showed a statistically significant effect on all Candida species compared to the control (DMSO) except for the lowest concentration (60 µg/µL) tested on C. glabrata. There was a dose-dependent effect of OLE on tested samples. Concentrations of 240 µg/µL and 333 µg/µL showed statistically significant higher antifungal activity compared to the lowest concentration of 60 µg/µL. No statistically significant synergistic effect of OLE and standard antifungal therapy was found compared with standard therapy alone. CONCLUSIONS: The results of this study present the significant antimicrobial effect of OLE against all tested Candida species except for the lowest concentration on C. glabrata. Increasing the concentration of OLE also increases its effect on Candida species. This indicates the possible potential effect of OLE in the treatment of Candida-related oral diseases.

Olive Leaf Extract Downregulates the Protein Expression of Key SARS-CoV-2 Entry Enzyme ACE-2, TMPRSS2, and Furin.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses ongoing global health challenges due to its propensity for mutations, which can undermine vaccine efficacy. With no definitive treatment available, urgent research into affordable and biocompatible therapeutic agents is extremely urgent. Angiotensin converting enzyme-2 (ACE-2), transmembrane protease serine subtype 2 (TMPRSS2), and Furin enzymes, which allow the virus to enter cells, are particularly important as potential drug targets among scientists. Olive leaf extract (OLE) has garnered attention for its potential against Coronavirus Disease-9 (COVID-19), yet its mechanism remains understudied. In this study, we aimed to investigate the effects of OLE on ACE-2, TMPRSS2, and Furin protein expressions by cell culture study. Total phenol, flavonoid content, and antioxidant capacity were measured by photometric methods, and oleuropein levels were measured by liquid LC-HR-MS. Cell viability was analyzed by ATP levels using a luminometric method. ACE-2, TMPRSS2, and Furin expressions were analyzed by the Western Blotting method. ACE-2, TMPRSS2, and Furin protein expression levels were significantly lower in a dose dependent manner and the highest inhibition was seen at 100 µg/ml OLE. The results showed that OLE may be a promising treatment candidate for COVID-19 disease. However, further studies need to be conducted in cells co-infected with the virus.

Olive leaf extract-derived chitosan-metal nanocomposite: Green synthesis and dual antimicrobial-anticancer action.

In this study, we developed a novel nanocomposite by synthesizing zinc (ZnNPs), copper (CuNPs), and silver (AgNPs) nanoparticles using olive leaf extract and incorporating them into a chitosan polymer. This approach combines the biocompatibility of chitosan with the antimicrobial and anticancer properties of metal nanoparticles, enhanced by the phytochemical richness of olive leaf extract. The significance of our research lies in its potential to offer a biodegradable and stable alternative to conventional antibiotics and cancer treatments, particularly in combating multidrug-resistant bacteria and various cancer types. Comprehensive characterization through Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), Thermogravimetric Analysis (TGA), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray (EDX), and Transmission Electron Microscopy (TEM) confirmed the successful synthesis of the nanocomposites, with an average size of ~22.6 nm. Phytochemical analysis highlighted the antioxidant-rich composition of both the olive leaf extract and the nanoparticles themselves. Functionally, the synthesized nanoparticles exhibited potent antimicrobial activity against multidrug-resistant bacterial strains, outperforming traditional antibiotics by inhibiting key resistance genes (ermC, tetX3-q, blaZ, and Ery-msrA). In anticancer assessments, the nanoparticles showed selective cytotoxicity towards cancer cells in a concentration-dependent manner, with CuNPs and AgNPs showing particularly strong anticancer effects, while demonstrating minimal toxicity towards normal cells. ZnNPs were noted for their low cytotoxicity, highlighting the safety profile of these nanoparticles. Further, the nanoparticles induced apoptosis in cancer cells, as evidenced by the modulation of oncogenes (P21, P53, and BCL2), suggesting their therapeutic potential. The findings of our study underscore the versatile applications of these biogenic nanoparticles in developing safer and more effective antimicrobial and anticancer therapies.

Beneficial Effect of Olive Oil and Its Derivates: Focus on Hematological Neoplasm.

Olive oil (Olea europaea) is one of the major components of the Mediterranean diet and is composed of a greater percentage of monounsaturated fatty acids, such as oleic acid; polyunsaturated fatty acids, such as linoleic acid; and minor compounds, such as phenolic compounds, and particularly hydroxytyrosol. The latter, in fact, are of greater interest since they have found widespread use in popular medicine. In recent years, it has been documented that phenolic acids and in particular hydroxytyrosol have anti-inflammatory, antioxidant, and antiproliferative action and therefore interest in their possible use in clinical practice and in particular in neoplasms, both solid and hematological, has arisen. This work aims to summarize and analyze the studies present in the literature, both in vitro and in vivo, on the possible use of minor components of olive oil in some hematological neoplasms. In recent years, in fact, interest in nutraceutical science has expanded as a possible adjuvant in the treatment of neoplastic pathologies. Although it is worth underlining that, regarding the object of our study, there are still few preclinical and clinical studies, it is, however, possible to document a role of possible interest in clinical practice.

Exploring the Nutritional and Bioactive Potential of Olive Leaf Residues: A Focus on Minerals and Polyphenols in the Context of Spain's Olive Oil Production.

Lyophilized plant-origin extracts are rich in highly potent antioxidant polyphenols. In order to incorporate them into food products, it is necessary to protect these phytochemicals from atmospheric factors such as heat, light, moisture, or pH, and to enhance their bioavailability due to their low solubility. To address these challenges, recent studies have focused on the development of encapsulation techniques for antioxidant compounds within polymeric structures. In this study, lyophilized olive leaf extracts were microencapsulated with the aim of overcoming the aforementioned challenges. The method used for the preparation of the studied microparticles involves external ionic gelation carried out within a water-oil (W/O) emulsion at room temperature. HPLC analysis demonstrates a high content of polyphenols, with 90% of the bioactive compounds encapsulated. Meanwhile, quantification by inductively coupled plasma optical emission spectroscopy (ICP-OES) reveals that the dried leaves, lyophilized extract, and microencapsulated form contain satisfactory levels of macro- and micro-minerals (calcium, potassium, sodium). The microencapsulation technique could be a novel strategy to harness the polyphenols and minerals of olive leaves, thus enriching food products and leveraging the antioxidant properties of the polyphenolic compounds found in the lyophilized extract.

Production of Acid and Rennet-Coagulated Cheese Enriched by Olive (Olea europaea L.) Leaf Extract-Determining the Optimal Point of Supplementation and Its Effects on Curd Characteristics.

This study investigated the potential of olive leaf extract (OLE), as a functional ingredient, to improve cheese properties, because it is rich in phenols. Milk and dairy products are poor in phenolic compounds. The main objective was to determine the most effective coagulation method and timing of OLE supplementation to maximize retention in the cheese matrix. Experimental cheeses were produced using the rennet and acid coagulation methods, with OLE added either directly to the cheese milk or to the curd phase. Three OLE effective concentrations corresponding to 25%, 50%, and 75% inhibition of DPPH reagent (EFC25, EFC50, and EFC75, respectively) were added, i.e., 11.5 mg GAE L-1, 16.6 mg GAE L-1, and 26.3 mg GAE L-1, respectively. The results showed that OLE significantly increased the concentration of total phenols, total flavonoids, and antioxidant activity in all cheese samples and in the residual whey, especially at higher effective concentrations (EFC 50 and EFC 75). Rennet-coagulated cheese to which OLE was added prior to coagulation (EM 25, EM 50, EM 75) exhibited higher hardness, gumminess, and chewiness but lower elasticity, suggesting alterations in the paracasein matrix. OLE did not adversely affect acidity, water activity, or cheese yield. However, higher EFC resulted in significant colour changes (∆E* > 3.0). In conclusion, the enrichment of cheesemaking milk with OLE and the application of the rennet coagulation method are the most suitable to optimise the production of OLE-enriched cheese. This research shows the potential to improve the nutritional value of cheese while maintaining its desired characteristics.

Olive leaf extract effect on cardiometabolic risk factors: a systematic review and meta-analysis of randomized clinical trials.

CONTEXT: Olive leaf extract (OLE) is rich in phenolic compounds, which are known for their health benefits. Cardiovascular diseases, primarily coronary heart disease and stroke, are leading causes of mortality globally. OBJECTIVE: This systematic review aimed to assess the impact of OLE on cardiometabolic risk factors in adults. The selection of studies was based on intervention and outcomes, using relevant search descriptors. DATA SOURCES: The databases PubMed, EMBASE, and Web of Science were systematically searched for pertinent studies published up to August 2021. DATA EXTRACTION: Only randomized clinical trials, either cross-over or parallel, involving adult individuals aged ≥18 years, were considered. Additionally, trials that had a comparative or placebo group and used pure OLEs for oral treatment were included. DATA ANALYSIS: Twelve randomized clinical trials (RCTs) met the inclusion criteria. These trials had follow-up periods ranging from 2 days to 12 weeks and involved 703 patients aged 18 years-79 years. The outcomes demonstrated a positive correlation between the intervention group and glucose metabolism (4 RCTs), blood pressure (2 RCTs), lipid profile (2 RCTs), and inflammatory markers (2 RCTs). The RoB2 tool and the GRADE system were used to evaluate the risk of bias and the quality of evidence in the studies. CONCLUSIONS: In the meta-analysis, fasting glycemia, as evaluated in studies using a low dose of OLE, showed a significant result favoring the control group. To obtain more consistent results, further clinical studies in humans, using similar methodologies, are required. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42020200877.

Expression of Na+/Ca2+ exchangers was enhanced following pre-treatment of olive leaf extract and olive oil in animal model of ischemic stroke.

BACKGROUND: Neuroprotective role of olive and its natural products can introduce them as alternative candidates for the management of neurodegenerative diseases including stroke. The present study was designed to evaluate whether pretreatment of olive oil and leaf extract can attenuate the most important destructive processes in cerebral ischemia called excitotoxicity. MATERIAL AND METHODS: The male rats were categorized into control, virgin olive oil (OVV), MCAO, MCAO + OVV (with doses of 0.25, 0.50 and 0.75 ml/kg as treatment groups), olive leaf extract, MCAO + olive leaf extract (with doses 50, 75 and 100 mg/kg as treatment groups) groups. Rats of treatment groups received gastric gavage with olive oil or leaf extract for 30 consecutive days. After pretreatment, the intraluminal filament technique was used to block middle cerebral artery (MCA) transiently. Neurological deficits, infarct volume and expression of Na+/Ca2+ exchangers (NCX1, NCX2 and NCX3) proteins were measured. RESULTS: The results revealed that olive oil at doses of 0.50 and 0.75 ml/kg reduced the infarction and neurological score and upregulated NCXs expression in rat brain. In addition, olive leaf extract at doses of 75 and 100 mg/kg attenuated the infarction and neurological score and enhanced NCXs expression in rat brain. CONCLUSION: These findings support the view that olive oil and leaf extract play the neuroprotective role in cerebral ischemia due to the upregulation of NCXs protein expression.

Effects of Enriched-in-Oleuropein Olive Leaf Extract Dietary Supplementation on Egg Quality and Antioxidant Parameters in Laying Hens.

The objective of the present study was to evaluate the effects of an olive leaf extract obtained with an up-to-date laboratory method, when supplemented at different levels in laying hens' diets, on egg quality, egg yolk antioxidant parameters, fatty acid content, and liver pathology characteristics. Thus, 96 laying hens of the ISA-Brown breed were allocated to 48 experimental cages with two hens in each cage, resulting in 12 replicates per treatment. Treatments were: T1 (Control: basal diet); T2 (1% olive leaf extract); T3 (2.5% olive leaf extract); T4 (Positive control: 0.1% encapsulated oregano oil). Eggshell weight and thickness were improved in all treatments compared to the control, with T2 being significantly higher till the end of the experiment (p < 0.001). Egg yolk MDA content was lower for the T2 and T4 groups, while total phenol content and Haugh units were greater in the T2. The most improved fatty acid profile was the one of T3 yolks. The α-tocopherol yolk content was higher in all groups compared to T1. No effect was observed on cholesterol content at any treatment. Based on the findings, it can be inferred that the inclusion of olive leaf extract at a concentration of 1% in the diet leads to enhancements in specific egg quality attributes, accompanied by an augmentation of the antioxidant capacity.

Hematinic Potential of Olive Leaf Extract: Evidence from an In Vivo Study in Mice and a Pilot Study in Healthy Human Volunteers.

Natural resources have recently received considerable attention as complementary or alternative hematinic agents. In this regard, olive leaf extract, which is rich in bioactive phenolic compounds, has been reported to induce erythroid differentiation in human hematopoietic stem cells. Therefore, in the present study, we aimed to explore the potential hematinic properties of aqueous olive leaf extract (WOL) in vivo. After 24 days of administering WOL to healthy mice orally, red blood cell (RBC), hematocrit, reticulocyte, and reticulocyte hemoglobin content (CHr) showed a significant increase. Additionally, WOL promoted plasma iron levels and the expression of splenic ferroportin (Fpn), an iron transporter. Additionally, a single-arm pilot study involving a limited number of healthy volunteers was conducted to assess WOL's feasibility, compliance, and potential benefits. Following an 8-week intervention with WOL, RBC count and hemoglobin level were significantly increased. Notably, there were no significant changes in the safety measures related to liver and kidney functions. Furthermore, we identified oleuropein and oleuroside as the active components in WOL to induce erythroid differentiation in the K562 cell line. Altogether, our study presents evidence of the hematinic potential of WOL in the in vivo studies, opening up exciting possibilities for future applications in preventing or treating anemia.

Effect of a Chitosan Coating Enriched with an Olive Leaf Extract on the Characteristics of Pork Burgers.

Chitosan coatings have been investigated for improving food shelf-life. The addition of an olive leaf extract could enhance its beneficial effect. The aim of this study was to evaluate the effectiveness of an olive leaf extract added to a chitosan coating in delaying deterioration in refrigerated pork burgers without additives packaged under a 40% oxygen and 60% carbon dioxide modified atmosphere. Some general parameters (microbial counts, instrumental color and texture, and lipid and protein oxidation) were measured over the storage of pork burgers without coating (Control), with a chitosan-based coating (Chitosan) and with a chitosan-based coating enriched with an olive leaf extract (Chitoex). The coating impacted the effect of the storage time on most parameters. Both coatings were especially effective at limiting the changes that occur over time in the headspace gases, some texture parameters (hardness, gumminess, and chewiness) and lipid oxidation, although the effect on the microbial counts was weak. Chitoex was more effective than Chitosan at preventing changes in the headspace gases on day 11 and in lipid oxidation on all the sampling days. In conclusion, the Chitoex coating could be useful for prolonging the storage of pork burgers by preventing changes in texture and reducing lipid oxidation.

Effects of Dietary Supplementation of a Resin-Purified Aqueous-Isopropanol Olive Leaf Extract on Meat and Liver Antioxidant Parameters in Broilers.

Olive leaves are byproducts οf the agro-industrial sector and are rich in bioactive compounds with antioxidant properties. They could be supplemented in poultry diets powdered or less frequently as extracts to improve performance, health and product quality. The objective of this study was to investigate the possible beneficial effects of an aqueous isopropanol olive leaf extract-purified through filtration (250-25 µm) and a resin (XAD-4)-when supplemented in broiler chickens' diets, on meat quality parameters, focusing mainly on antioxidant parameters as there is limited published information. For this purpose, four-hundred-and-eighty-day-old broilers were randomly assigned to four dietary treatments: T1 (control: basal diet); T2 (1% olive leaf extract); T3 (2.5% olive leaf extract); T4 (positive control: 0.1% encapsulated oregano oil commercially used as feed additive). At the end of the experimental period (day 42), the birds were slaughtered, and samples from breast, thigh meat and liver were collected for antioxidant parameters evaluation. On day 1, after slaughter, in thigh meat, Malondialdehyde (MDA) was lower in T2 compared to T3, and total phenolic content (TPC) was higher in T2 compared to T3 and T4. Total antioxidant capacity (TAC) was increased in T2 and T4 breast meat compared to the control. In liver, T4 treatment resulted in higher TPC. The lack of dose-dependent effect for olive leaf extract may be attributed to the pro-oxidant effects of some bioactive compounds found in olive leaves, such as oleuropein, when supplemented at higher levels. In summary, it can be inferred that the inclusion of 1% olive leaf extract in the feed of broilers has the potential to mitigate oxidation in broiler meat and maybe enhance its quality.

Anti-Inflammatory Effects of Olive Leaf Extract and Its Bioactive Compounds Oleacin and Oleuropein-Aglycone on Senescent Endothelial and Small Airway Epithelial Cells.

Olive tree by-products have been deeply studied as an invaluable source of bioactive compounds. Several in vitro and in vivo studies showed that olive leaf extract (OLE) has anti-inflammatory and antioxidant properties. Here, we wanted to assess the valuable benefits of two less-studied OLE components-3,4-DHPEA-EDA (Oleacin, OC) and 3,4-DHPEA-EA (Oleuropein-Aglycone, OA)-directly purified from OLE using a cost-effective and environmentally sustainable method, in line with the principles of circular economy. OLE, OC and OA were then tested in human cellular models involved in acute and chronic inflammation and in the pathogenesis of viral infections, i.e., lipopolysaccharide (LPS)-treated monocyte/macrophages (THP-1) and endothelial cells (HUVECs), senescent HUVECs and Poly(I:C)-treated small airway epithelial cells (hSAECs). Results showed that OC and OA are efficient in ameliorating almost all of the pro-inflammatory readouts (IL-1ß, TNF-α, IL-8, ICAM, VCAM) and reducing the release of IL-6 in all the cellular models. In hSAECs, they also modulate the expression of SOD2, NF-kB and also ACE2 and TMPRSS2, whose expression is required for SARS-CoV-2 virus entry. Overall, these data suggest the usefulness of OLE, OC and OA in controlling or preventing inflammatory responses, in particular those associated with viral respiratory infections and aging.

Development of Pegylated Nano-Phytosome Formulation with Oleuropein and Rutin to Compare Anti-Colonic Cancer Activity with Olea Europaea Leaves Extract.

Olive leaf extract is a valuable source of phenolic compounds; primarily, oleuropein (major component) and rutin. This natural olive leaf extract has potential use as a therapeutic agent for cancer treatment. However, its clinical application is hindered by poor pharmacokinetics and low stability. To overcome these limitations, this study aimed to enhance the anticancer activity and stability of oleuropein and rutin by loading them into PEGylated Nano-phytosomes. The developed PEGylated Nano-phytosomes exhibited favorable characteristics in terms of size, charge, and stability. Notably, the anticolonic cancer activity of the Pegylated Nano-phytosomes loaded with oleuropein (IC50=0.14 µM) and rutin (IC50=0.44 µM) surpassed that of pure oleuropein and rutin alone. This outcome highlights the advantageous impact of Nano-phytosomes to augment the anticancer potential of oleuropein and rutin. These results present a promising pathway for the future development of oleuropein and rutin Nano-phytosomes as effective options for passive tumor-targeted therapy, given their improved stability and efficacy.

Olive Leaf Extract (OLE) as a Novel Antioxidant That Ameliorates the Inflammatory Response in Cystic Fibrosis.

The deletion of phenylalanine at position 508 (F508del) produces a misfolded CFTR protein that is retained in the ER and degraded. The lack of normal CFTR channel activity is associated with chronic infection and inflammation which are the primary causes of declining lung function in Cystic Fibrosis (CF) patients. Moreover, LPS-dependent oxidative stress downregulates CFTR function in airway epithelial cells. Olive leaf extract (OLE) is used in traditional medicine for its effects, including anti-oxidant and anti-inflammatory ones. We found that OLE decreased the intracellular ROS levels in a dose-response manner in CFBE cells. Moreover, OLE attenuates the inflammatory response to LPS or IL-1ß/TNFα stimulation, mimicking the infection and inflammatory status of CF patients, in CFBE and primary nasal epithelial (HNE) cells. Furthermore, we demonstrated that OLE restored the LPS-mediated decrease of TrikfaftaTM-dependent F508del-CFTR function in CFBE and HNE cultures. These findings provide strong evidence of OLE to prevent redox imbalance and inflammation that can cause chronic lung damage by enhancing the antioxidant activity and attenuating inflammation in CF airway epithelial cells. Additionally, OLE might be used in combination with CFTR modulators therapy to improve their efficacy in CF patients.

Dietary Olive Leaf Extract Differentially Modulates Antioxidant Defense of Normal and Aeromonas hydrophila-Infected Common Carp (Cyprinus carpio) via Keap1/Nrf2 Pathway Signaling: A Phytochemical and Biological Link.

Olive leaves are an immense source of antioxidant and antimicrobial bioactive constituents. This study investigated the effects of dietary incorporation of olive leaf extract (OLE) on the growth performance, hematobiochemical parameters, immune response, antioxidant defense, histopathological changes, and some growth- and immune-related genes in the common carp (Cyprinus carpio). A total of 180 fish were allocated into four groups with triplicate each. The control group received the basal diet without OLE, while the other three groups were fed a basal diet with the OLE at 0.1, 0.2, and 0.3%, respectively. The feeding study lasted for 8 weeks, then fish were challenged with Aeromonas hydrophila. The results revealed that the group supplied with the 0.1% OLE significantly exhibited a higher final body weight (FBW), weight gain (WG%), and specific growth rate (SGR) with a decreased feed conversion ratio (FCR) compared to the other groups (p < 0.05). An increase in immune response was also observed in the fish from this group, with higher lysosome activity, immunoglobulin (IgM), and respiratory burst than nonsupplemented fish, both before and after the A. hydrophila challenge (p < 0.05). Similarly, the supplementation of the 0.1% OLE also promoted the C. carpio's digestive capacity pre- and post-challenge, presenting the highest activity of protease and alkaline phosphatase (p < 0.05). In addition, this dose of the OLE enhanced fish antioxidant capacity through an increase in the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and decreased hepatic lipid peroxidation end products (malondialdehyde-MDA), when compared to the control group, both pre- and post-infection (p < 0.05). Concomitantly with the superior immune response and antioxidant capacity, the fish fed the 0.1% OLE revealed the highest survival rate after the challenge with A. hydrophila (p < 0.05). A significant remarkable upregulation of the hepatic sod, nrf2, and protein kinase C transcription levels was detected as a vital approach for the prevention of both oxidative stress and inflammation compared to the infected unsupplied control group (p < 0.05). Interestingly, HPLC and UPLC-ESI-MS/MS analyses recognized that oleuropein is the main constituent (20.4%) with other 45 compounds in addition to tentative identification of two new compounds, namely oleuroside-10-carboxylic acid (I) and demethyl oleuroside-10-carboxylic acid (II). These constituents may be responsible for the OLE exerted potential effects. To conclude, the OLE at a dose range of 0.66-0.83 g/kg w/w can be included in the C. carpio diet to improve the growth, antioxidant capacity, and immune response under normal health conditions along with regulating the infection-associated pro-inflammatory gene expressions, thus enhancing resistance against A. hydrophila.

Low Dose Monacolin K Combined with Coenzyme Q10, Grape Seed, and Olive Leaf Extracts Lowers LDL Cholesterol in Patients with Mild Dyslipidemia: A Multicenter, Randomized Controlled Trial.

Certain nutraceuticals, mainly containing red yeast rice, might be considered as an alternative therapy to statins in patients with dyslipidemia, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. The aim of this study was to assess the lipid-lowering activity and safety of a dietary supplement containing a low dose of monacolin K combined with coenzyme Q10, grape seed and olive tree leaf extracts in patients with mild hypercholesterolemia. In total, 105 subjects with mild hypercholesterolemia (low-density lipoprotein cholesterol LDL-C levels 140-180 mg/dL) and low CV risk were randomly assigned into three treatment groups: lifestyle modification (LM), LM plus a low dosage of monacolin K (3 mg), and LM plus a high dosage of monacolin K (10 mg) and treated for 8 weeks. The primary endpoint was the reduction of LDL-C and total cholesterol (TC). LDL-C decreased by 26.46% on average (p < 0.001) during treatment with 10 mg of monacolin and by 16.77% on average during treatment with 3 mg of monacolin (p < 0.001). We observed a slight but significant reduction of the triglyceride levels only in the high-dose-treated group (mean -4.25%; 95% CI of mean -11.11 to 2.61). No severe adverse events occurred during the study. Our results confirm the LDL-C-lowering properties of monacolin are clinically meaningful even in lower doses of 3 mg/day.

Comparative analysis of Ag NPs functionalized with olive leaf extract and oleuropein and toxicity in human trophoblast cells and peripheral blood lymphocytes.

Dry olive leaf extract (DOLE) and its active component oleuropein (OLE) were applied as reducing and stabilizing agents to prepare colloidal 20-25 nm silver nanoparticles (Ag NPs). The Ag NPs were characterized using transmission electron microscopy, X-ray diffraction analysis, and absorption spectroscopy. The cytotoxic actions of coated Ag NPs, and their inorganic and organic components, were examined against trophoblast cells and human peripheral blood lymphocytes (PBLs), Gram-positive, Gram-negative bacteria, and yeast. The genotoxic potential was evaluated in PBLs in vitro with the comet assay. Ag/DOLE and Ag/OLE induced cytotoxic effects in both types of cells after 24 h exposure when silver concentrations were 0.025-0.2 mM. However, the most pronounced cytotoxicity exhibits Ag/OLE. Both colloids also caused reduced ROS production in both cell types at 0.1 mM and 0.2 mM, while bare Ag NPs did not alter ROS levels at any of the conditions. Functionalized Ag/DOLE and Ag/OLE did not show genotoxic effects in PBLs, while bare AgNPs increased DNA damage significantly only at 0.2 mM. Regarding the antimicrobial effects, the Ag/OLE had MIC values for all evaluated microorganisms from 0.0625 to less than 0.0312 mM. Also, the antimicrobial effect of Ag/DOLE was significantly higher on Gram-negative bacteria and yeast than on Gram-positive bacteria. Obtained results indicate that Ag/OLE induced the most pronounced biological effects, beneficial for its application as an antimicrobial agent, but with potential risks from exposure to high concentrations that could induce cytotoxicity in healthy human cells.

Designing Antioxidant and Antimicrobial Polyethylene Films with Bioactive Compounds/Clay Nanohybrids for Potential Packaging Applications.

In the present work, direct incorporation of bioactive compounds onto the surface and interlayer of nanoclays before their incorporation into the final polymeric film was conducted, based on a green methodology developed by our group that is compatible with food packaging. This will lead to the higher thermal stability and the significant reduction of the loss of activity of the active ingredients during packaging configuration. On this basis, the essential oil (EO) components carvacrol (C), thymol (T) as well as olive leaf extract (OLE), which is used for the first time, were incorporated onto organo-modified montmorillonite (O) or inorganic bentonite (B) through the evaporation/adsorption method. The prepared bioactive nanocarriers were further mixed with low-density polyethylene (LDPE), via melt compounding, in order to prepare films for potential use as fresh fruit and vegetable packaging material. Characterization of the bioactive nanocarriers and films were performed through XRD, TGA, tensile, antimicrobial and antioxidant tests. Films with organically modified montmorillonite loaded with carvacrol (OC), thymol (OT) and olive leaf extract (OOLE) at 5% wt. showed better results in terms of mechanical properties. The films with polyethylene and organically modified montmorillonite loaded with carvacrol or thymol at 20% wt. (PE_OC20 and PE_OT20), as well as with olive leaf extract at 5 or 10 %wt., clay:bioactive substance ratio 1:0.5 and 10% compatibilizer (PE_OOLE5_MA10 and PE_OOLE10_MA10) exhibited the highest antioxidant activity. The resulting films displayed outstanding antimicrobial properties against Gram-negative Escherichia coli (E. coli) with the best results appearing in the films with 10% OC and OT.