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There is still a great global need for efficient treatments for the management of SARS-CoV-2 illness notwithstanding the availability and efficacy of COVID-19 vaccinations. Olive leaf is an herbal remedy with a potential antiviral activity that could improve the recovery of COVID-19 patients. In this work, the olive leaves major metabolites were screened in silico for their activity against SARS-CoV-2 by molecular docking on several viral targets such as methyl transferase, helicase, Pl pro , M pro , and RdRp. The results of in silico docking study showed that olive leaves phytoconstituents exhibited strong potential antiviral activity against SARS-CoV-2 selected targets. Verbacoside demonstrated a strong inhibition against methyl transferase, helicase, Pl pro , M pro , and RdRp (docking scores = -17.2, -20, -18.2, -19.8, and -21.7 kcal/mol.) respectively. Oleuropein inhibited 5rmm, M pro , and RdRp (docking scores = -15, -16.6 and -18.6 kcal/mol., respectively) respectively. Apigenin-7- O -glucoside exhibited activity against methyl transferase and RdRp (docking score = -16.1 and -19.4 kcal/mol., respectively) while Luteolin-7- O -glucoside inhibited Pl pro and RdRp (docking score = -15.2 and -20 kcal/mol., respectively). The in vitro antiviral assay was carried out on standardized olive leaf extract (SOLE) containing 20% oleuropein and IC 50 was calculated. The results revealed that 20% SOLE demonstrated a moderate antiviral activity against SARS-CoV-2 with IC 50 of 118.3 μ g /mL. Accordingly, olive leaf could be a potential herbal therapy against SARS-CoV-2 but more in vivo and clinical investigations are recommended.

The main objectives of this study were to develop an optimized green extraction process to obtain high contents of oleuropein and flavonoids from olive leaves. A deep eutectic solvent (DES) combined with wall-breaking extraction (WBE) was employed. A DES composed of choline chloride and ethylene glycol in a 1:2 molar ratio with 30% moisture content outperformed lactic acid and methanol as extraction solvents. The optimal conditions, determined by response surface methodology, were 30% moisture content, 140 s of wall-breaking time, and a 230 mL/g liquid–solid ratio. Under these conditions, 88.87 mg/g DM oleuropein, 4.57 mg/g DM luteolin-7-O-glucoside, and 114.31 mg RE/g total flavonoids were obtained. Among three olive varieties (Arbosana, Arbequina, and Picholine) cultivated in China, young Picholine leaves exhibited the highest contents. The Picholine-enriched extract demonstrated higher antioxidant activity (ABTS•+ 155.10 mg/mL, DPPH• 44.58 mg/mL) compared to other DES-based extracts, although it was lower than that of purified compounds. Furthermore, the CCK-8 assay revealed significant inhibition of Eca-109 human esophageal cells by the Picholine-enriched extract at 25 µg/mL for 24 h, compared to Het-1A cells. This process effectively recovers bioactive compounds from olive by-product, and shows potential for applications in nutritional supplements, cosmetics, and the food industry.

Oleuropein plays a key role as a pro-oxidant as well as an antioxidant in cancer. In this study, the activity of oleuropein, in an in vitro model of ovarian (OCCs) and breast cancer cells (BCCs) was investigated. Cell viability and cell death were analyzed. Oxidative stress was measured by CM-H2DCFDA flow cytometry assay. Mitochondrial dysfunction was evaluated based on mitochondrial reactive oxygen species (ROS) and GPX4 protein levels. Further, the effects on iron metabolism were analyzed by measuring the intracellular labile iron pool (LIP). We confirmed that high doses of oleuropein show anti-proliferative and pro-apoptotic activity on HEY and MCF-7 cells. Moreover, our results indicate that low doses of oleuropein impair cell viability without affecting the mortality of cells, and also decrease the LIP and ROS levels, keeping them unchanged in MCF-7 cells. For the first time, our data show that low doses of oleuropein reduce erastin-mediated cell death. Interestingly, oleuropein decreases the levels of intracellular ROS and LIP in OCCs treated with erastin. Noteworthily, we observed an increased amount of ROS scavenging enzyme GPX4 together with a consistent reduction in mitochondrial ROS, confirming a reduction in oxidative stress in this model.

Doxorubicin (DOX) is the most used chemotherapeutic agent for treating solid tumors. DOX treatment may lead to testicular damage using oxidative stress, resulting in infertility. These adverse effects may be prevented by the activation of antioxidant systems.Oleuropein (OLE) is a powerful flavonoid with several ameliorative effects, including antioxidative, antiproliferative, and anti-inflammatory. It would be more efficient and applicable in treating chronic human diseases if its poor bioavailability improves with a nano-delivery system. The current study aims to assess the histopathological changes and antioxidative effects of OLE loaded with silver nanoparticles oleuropein (OLE-AgNP) on the testicular injury triggered by DOX in rats.Forty-eight male albino rats were randomly divided into six groups as follows: the control, DOX (2.5 mg/kg), OLE (50 mg/kg), AgNP (100 mg/kg), OLE + AgNP (50 mg/kg), OLE (50 mg/kg) + DOX (2.5 mg/kg), AgNP (100 mg/kg) + DOX (2.5 mg/kg), and OLE-AgNP (50 mg/kg) + DOX (2.5 mg/kg) for 11 days. Oxidative stress, inflammation, apoptosis, endoplasmic reticulum stress markers, sperm analysis, and histopathological analyses were performed on testicular tissues taken from rats decapitated after the applications and compared between the experimental groups. The tissue MDA level was lower in the OLE and OLE+AgNP-treated groups than in the DOX-treated group. In addition, SOD and GSH levels significantly increased in both the OLE and OLE+AgNP-treated groups compared to the DOX group.Both OLE and OLE+AgNP, particularly OLE+AgNP, ameliorated DOX-induced testicular tissue injury, as evidenced by reduced injury and improved seminiferous tubules and spermatocyte area. In addition, OLE and OLE+AgNP, especially OLE+AgNP, inhibited DOX-induced testicular tissue inflammation, apoptosis, and endoplasmic reticulum stress.The findings suggest that nanotechnology and the production of OLE+AgNP can ameliorate DOX-induced testicular damage.

This study investigated the cardioprotective effect of oleuropein against cisplatin-induced cardiac damage in terms of inflammatory, oxidative stress and cardiac parameters. In this study, 40 female Wistar albino rats were divided into four groups: control, cisplatin, oleuropein and cisplatin+oleuropein. To establish the experimental model, oleuropein (200 mg/kg) was administered for 14 days and cisplatin (7 mg/kg) was administered as a single dose on the seventh day. Cisplatin increased MDA cardiac parameters (CK, CK-MB and cTnI) and inflammatory cytokines (TNF-α, IL-1β and IL-6) in cardiac tissue and decreased GSH, GSH-Px and catalase levels. On the other hand, oleuropein improved cardiac parameters and decreased inflammatory cytokine and oxidative stress levels in cardiac tissue.

Ultraviolet B (UVB) exposure induces skin photoaging through triggering oxidative stress, inflammation, apoptosis, and collagen degradation. Oleuropein (OLE), Hydroxytyrosol (HT), and Verbascoside (Verb) are polyphenols derived from olive leaves, exhibiting potent antioxidant and anti-inflammatory properties. In the present study, we investigated the protective effects of OLE, HT, and Verb combination (O/H/V) against UVB-induced photoaging using in vitro models. The results showed that O/H/V treatment reduced the expression of senescence and apoptosis-related markers, while concurrently downregulated inflammatory factors and matrix metalloproteinases via suppression of MAPK and NF-κB pathways in UVB-irradiated HDF cells. In UVB-irradiated HaCaT cells, O/H/V treatment attenuated collagen degradation and pro-inflammatory factors expression via upregulation of Nrf2 levels. Furthermore, in a HaCaT-HDFs co-culture system, treatment of UVB-irradiated HaCaT cells with the O/H/V combination led to a significant reduction in pro-inflammatory factors and collagen degradation-related genes in HDFs. Together, these findings indicate that the O/H/V combination exerts protection against UVB-induced photoaging through multiple mechanisms, including inhibition of MAPK/NF-κB pathway and enhancement of Nrf2 expression.

Oleuropein (OLP) is a naturally occurring phenolic compound in olive plant with antioxidant and anti-inflammatory potential and can possibly be used in treating pancreatic injuries. This investigation aimed to follow the molecular mechanism behind the potential therapeutic effect of OLP against pancreatic injury persuaded by ischemia–reperfusion (I/R). Pancreatic I/R injury was induced by splenic artery occlusion for 60 min followed by reperfusion. Oral administration of OLP (10 and 20 mg/kg) for 2 days significantly alleviated I/R-persuaded oxidative damage and inflammatory responses in pancreatic tissue as indicated by the decreased malondialdehyde (MDA) content and increased glutathione peroxidase (GPx) activity, accompanied by the suppression of myeloperoxidase (MPO) activity and reduced levels of interleukin-1beta (IL-1β), nuclear factor kappa B (NF-κB), and tumor necrosis factor alpha (TNF-α) in pancreatic tissues. Furthermore, OLP treatment markedly restored the serum levels of amylase, trypsinogen-activated peptide (TAP), and lipase, with concurrent improvement in pancreatic histopathological alterations. Moreover, treatment with OLP regulated the pancreatic expression of inducible nitric oxide synthase (iNOS) and high-mobility group box 1 (HMGB1) relative to rats of the pancreatic IR group. Thus, OLP treatment significantly alleviates the I/R-induced pancreatic injury by inhibiting oxidative stress and inflammation in rats through downregulation of HMGB1 and its downstream NF-κB signaling pathway.

Human immunity involves both innate and adaptive defence mechanisms, with inflammation playing a central role in responding to cellular injury, pathogenic infections, and allergic stimuli. Reactive oxygen species (ROS) are closely associated with the onset and progression of inflammation. While moderate ROS levels function as crucial signalling molecules, excessive ROS can damage cellular components. This study aimed to evaluate the anti-inflammatory and antioxidant potential of plant-derived bioactive compounds including chlorogenic acid, oleuropein, tomatine, and tyrosol using human monocytic cell models (U-937 and THP-1). Differentiation of U-937 and THP-1 cells was induced prior to treatment with the selected bioactive compounds. Cell morphology and integrity were examined utilizing confocal microscopy. Gene expression stability was evaluated using reference genes β-actin and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Protein expression levels of key inflammatory markers were determined by Western blot analysis. In addition, molecular docking studies were conducted to assess the binding affinity of the compounds to human target proteins [Interleukin-4 (IL-4), 5-Lipoxygenase (LOX-5), Myeloperoxidase (MPO), and Tumor necrosis factor-alpha ( TNF-α)]. No cytotoxic effects were observed in treated cells, and GAPDH was confirmed as a stable reference gene under all experimental conditions. In U-937 cells, treatment with the bioactive compounds led to increased expression of the anti-inflammatory cytokine IL-4 and decreased expression of MPO. Notably, exposure to chlorogenic acid and tyrosol reduced MPO activity. Oleuropein and tyrosol demonstrated a strong suppressive effect on the expression of LOX-5, an enzyme responsible for leukotriene production. All tested bioactive compounds significantly reduced the phorbol 12-myristate 13-acetate (PMA) induced increase in LOX-5 activity. Molecular docking supported the potential of these compounds to interact with key inflammatory proteins, contributing to reduced oxidative stress. The plant-derived compounds, particularly oleuropein and tyrosol from olives, exhibit promising anti-inflammatory and antioxidant effects by modulating ROS-associated signalling pathways and downregulating inflammatory markers. These findings support the therapeutic potential of agricultural waste-derived bioactive in inflammation management and oxidative stress regulation.

This study aimed to address the challenges of treating advanced stages of colon cancer (CRC) by exploring potential therapeutic options. The research focused on the genetic aspects of CRC, specifically the mutation rate of the KRAS gene, along with other genes like TTN , APC , MUC16 , and TP53, using the TCGA dataset. Additionally, the study investigated the efficacy of Oleuropein, a polyphenolic compound found in olives, in combating CRC by using iron oxide nanoparticles coated with glucose and conjugated with Oleuropein. The study characterized the physicochemical properties of the nanoparticles, and the cytotoxic effects of the nanoparticles were evaluated on CRC and normal fibroblast cell lines, demonstrating significantly higher cytotoxicity against CRC cells compared to normal cells. Furthermore, the study analyzed gene expression changes using the GSE124627 dataset to understand the influence of KRAS alterations. It identified numerous upregulated and downregulated genes in KRAS-overexpressing samples, suggesting their involvement in critical cancer-related pathways. These findings suggest that KRAS -influenced genes could serve as potential therapeutic targets for CRC treatment. The study also examined the expression levels of identified genes in CRC samples compared to normal samples. Among the upregulated genes, 22 showed significant increases in cancer samples, while 14 downregulated genes exhibited decreased expression in both KRAS-influenced and cancer samples. Cox regression analysis identified specific upregulated genes, including ANKZF1 , SNAI1 , PPFIA4 , SIX4 , and NOTUM , associated with poor prognosis. Kaplan-Meier analysis further confirmed the correlation between increased expression of these genes and higher patient mortality rates. In conclusion, this study provided valuable insights into the genetic aspects of CRC and potential therapeutic strategies. The use of Oleuropein-conjugated iron oxide nanoparticles showed promising cytotoxic effects on colon cancer cells. These findings contribute to advancing our understanding of CRC and offer potential targets for further investigation and the development of novel therapeutic approaches.

Gut-dysbiosis-induced lipopolysaccharides (LPS) translocation into systemic circulation has been suggested to be implicated in nonalcoholic fatty liver disease (NAFLD) pathogenesis. This study aimed to assess if oleuropein (OLE), a component of extra virgin olive oil, lowers high-fat-diet (HFD)-induced endotoxemia and, eventually, liver steatosis. An immunohistochemistry analysis of the intestine and liver was performed in (i) control mice (CTR; n = 15), (ii) high-fat-diet fed (HFD) mice (HFD; n = 16), and (iii) HFD mice treated with 6 µg/day of OLE for 30 days (HFD + OLE, n = 13). The HFD mice developed significant liver steatosis compared to the controls, an effect that was significantly reduced in the HFD + OLE-treated mice. The amount of hepatocyte LPS localization and the number of TLR4+ macrophages were higher in the HFD mice in the than controls and were lowered in the HFD + OLE-treated mice. The number of CD42b+ platelets was increased in the liver sinusoids of the HFD mice compared to the controls and decreased in the HFD + OLE-treated mice. Compared to the controls, the HFD-treated mice showed a high percentage of intestine PAS+ goblet cells, an increased length of intestinal crypts, LPS localization and TLR4+ expression, and occludin downregulation, an effect counteracted in the HFD + OLE-treated mice. The HFD-fed animals displayed increased systemic levels of LPS and zonulin, but they were reduced in the HFD + OLE-treated animals. It can be seen that OLE administration improves liver steatosis and inflammation in association with decreased LPS translocation into the systemic circulation, hepatocyte localization of LPS and TLR4 downregulation in HFD-induced mouse model of NAFLD.