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Mechanism of the antiviral effect of hydroxytyrosol on influenza virus appears to involve morphological change of the virus

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Abstract

Hydroxytyrosol (HT), a small-molecule phenolic compound, inactivated influenza A viruses including H1N1, H3N2, H5N1, and H9N2 subtypes. HT also inactivated Newcastle disease virus but not bovine rotavirus, and fowl adenovirus, suggesting that the mechanism of the antiviral effect of HT might require the presence of a viral envelope. Pretreatment of MDCK cells with HT did not affect the propagation of H9N2 virus subsequently inoculated onto the cells, implying that HT targets the virus but not the host cell. H9N2 virus inactivated with HT retained unaltered hemagglutinating activity and bound to MDCK cells in a manner similar to untreated virus. Neuraminidase activity in the HT-treated virus also remained unchanged. However, in the cells inoculated with HT-inactivated H9N2 virus, neither viral mRNA nor viral protein was detected. Electron microscopic analysis revealed morphological abnormalities in the HT-treated H9N2 virus. Most structures found in the HT-treated virus were atypical of influenza virions, and localization of hemagglutinin was not necessarily confined on the virion surface. These observations suggest that the structure of H9N2 virus could be disrupted by HT.

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... Yamada et al. demonstrated that hydroxytyrosol (HT) was able to inactivate different influenza A viruses, including H1N1, H3N2, H5N1, and H9N2, and also the Newcastle disease virus, suggesting that the mechanism of the antiviral effect of this polyphenol may require the presence of a viral envelope for its action [55]. At the same time, a pre-treatment of MDCK (Madin-Darby Canine Kidney cells) with HT did not affect the spread of H9N2 when subsequently inoculated; although, the H9N2 virus inactivated with hydroxytyrosol maintained its hemagglutinating activity unaltered and bound to MDCK cells in a similar way to untreated virus, implying that HT targets the virus and not the host cell [55]. ...
... Yamada et al. demonstrated that hydroxytyrosol (HT) was able to inactivate different influenza A viruses, including H1N1, H3N2, H5N1, and H9N2, and also the Newcastle disease virus, suggesting that the mechanism of the antiviral effect of this polyphenol may require the presence of a viral envelope for its action [55]. At the same time, a pre-treatment of MDCK (Madin-Darby Canine Kidney cells) with HT did not affect the spread of H9N2 when subsequently inoculated; although, the H9N2 virus inactivated with hydroxytyrosol maintained its hemagglutinating activity unaltered and bound to MDCK cells in a similar way to untreated virus, implying that HT targets the virus and not the host cell [55]. ...
... Electron microscopy analysis showed morphological abnormalities in the HT-treated H9N2 virus, with most of the structures found in the virions being atypical. These results suggest that the viral structure is altered by HT [55]. ...
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There is currently a worldwide consensus and recognition of the undoubted health benefits of the so-called Mediterranean diet, with its intake being associated with a lower risk of mortality. The most important characteristics of this type of diet are based on the consumption of significant amounts of fruit, vegetables, legumes, and nuts, which provide, in addition to some active ingredients, fiber and a proportion of vegetable protein, together with extra virgin olive oil (EVOO) as the main sources of vegetable fat. Fish and meat from poultry and other small farm animals are the main sources of protein. One of the main components, as already mentioned, is EVOO, which is rich in monounsaturated fatty acids and to a lesser extent in polyunsaturated fatty acids. The intake of this type of nutrient also provides an important set of phytochemicals whose health potential is widely spread and agreed upon. These phytochemicals include significant amounts of anthocyanins, stilbenes, flavonoids, phenolic acids, and terpenes of varying complexities. Therefore, the inclusion in the diet of this type of molecules, with a proven healthy effect, provides an unquestionable preventive and/or curative activity on an important group of pathologies related to cardiovascular, infectious, and cancerous diseases, as well as those related to the metabolic syndrome. The aim of this review is therefore to shed light on the nutraceutical role of two of the main phytochemicals present in Olea europaea fruit and leaf extracts, polyphenols, and triterpenes, on healthy animal growth. Their immunomodulatory, anti-infective, antioxidant, anti-aging, and anti-carcinogenic capabilities show them to be potential nutraceuticals, providing healthy growth.
... Olive polyphenols are also known to play a role in preventing chronic human diseases such as cardiovascular diseases and inflammatory diseases [6]. Several in vitro and in vivo studies confirmed that phenolic compounds from olive reduce the effect of oxidative stress associated with pathological disorders including atherosclerosis [7,8], cancer [9,10], inflammatory diseases [11][12][13], neurodegenerative diseases [14], and they have some anti-microbial and anti-viral properties [15][16][17][18]. ...
... A large number of methods have been developed for measure ROS production, which are based on detection by colorimetry, fluorescence or chemiluminescence, depending on the probe used [16][17][18][19][20]. The ideal technique should be highly sensitive, specific for one ROS species, and should not interfere with cellular functions. ...
... The ideal technique should be highly sensitive, specific for one ROS species, and should not interfere with cellular functions. Among these techniques, luminolamplified chemiluminescence has been largely used to detect ROS production [16][17][18][19]. Luminol (5-amino-2,3-dihydro-1,4-phthalazine-dione) is a redox-sensitive compound that emits blue luminescence when oxidized. ...
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Olive mill wastewater (OMW) is produced seasonally by the olive oil producing countries. A large amount of liquid waste results from olive oil extraction, with a very high organic load which renders it difficult to treat. Wastewater represents also a significant source of polyphenols (pp). Oleuropein and hydroxytyrosol are polyphenols wich are major biological active components of olives, olive oil and OMW.The extraction of polyphenols will improve the wastewater biodegradation and reduce its phytotoxicity. The aim of this study was to extract pp from OMW and investigate the effect of this extract, hydroxytyrosl and oleurpeine on human polynuclear neutrophil (PN) functions such as reactive oxygen species (ROS) production, degranulation and chemotaxis. PN were isolated from healthy donors and were incubated with increased concentrations of polyphenol extract or hydroxytyrosol and oleuropeine. ROS production was measured by luminol-amplified chemiluminescence, cytochrome c reduction, and flow cytometer. Hydroxytyrosol and oleuropeine are tested on other PN functions: degranulation was assessed by measuring myeloperoxidase activity and Western blots, chemotaxis was assessed by the under-agarose chemotaxis assay. Phosphorylated proteins were assessed by gel electrophoresis and Western blots. Our results showed that pp extracted from OMW exerts a strong antioxidant effect and they could have an anti-inflammatory effect by inhibiting PN ROS production by scavenging hydrogen peroxide, thus limiting their toxic effects. We show that in addition to their ROS scavenging effect, oleuropein and hydroxytyrosol significantly inhibited the bacterial peptide N-formyl-methionyl-leucylphenylalanine (fMLF)-induced degranulation of azurophilic and specific granules as measured by myeloperoxidase and lactoferrin release, respectively. We also show that oleuropein and hydroxytyrosol reduced fMLF-induced neutrophil chemotaxis. Interestingly, both agents impaired the fMLF-induced AKT, p38MAPKinase, and ERK1/2 phosphorylation, signaling molecules that are involved in pathways regulating PN functions. Our data suggest that the anti-inflammatory properties of olive pp are not only restricted to their ROS scavenging effect, but also involve the inhibition of two other major pro-inflammatory PN functions.
... Hydroxytyrosol can also have antiviral activity. Certain research studies 33 suggest that the mechanism of this effect might require the presence of a viral envelope. ...
... The influenza virus protein has a binding site for hydroxytyrosol in the domain essential for cell entry, which means that hydroxytyrosol affects the influenza virus. The results obtained in this study also suggest that the antiviral effect of hydroxytyrosol on the H9N2 virus can be attributed to the direct effect of hydroxytyrosol on the virus 33 . The morphology of the hydroxytyrosol-treated H9N2 virus has been analyzed under the electron microscope. ...
... The results suggested that the structure of the viral envelope could be disrupted by hydroxytyrosol. Suppression of viral mRNA synthesis and lack of viral nucleoprotein observed in cells inoculated with hydroxytyrosol-treated H9N2 virus may be the result of poor viral binding, viral uncoating or problems with other steps of viral infection 33 . ...
Article
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Objective: The aim of the study was to show the effect that two naturally occurring compounds, a cyclodextrin and hydroxytyrosol, can have on the entry of SARS-CoV-2 into human cells. Materials and methods: The PubMed database was searched to retrieve studies published from 2000 to 2020, satisfying the inclusion criteria. The search keywords were: SARS-CoV, SARS-CoV-2, coronavirus, lipid raft, endocytosis, hydroxytyrosol, cyclodextrin. Modeling of alpha-cyclodextrin and hydroxytyrosol were done using UCSF Chimera 1.14. Results: The search results indicated that cyclodextrins can reduce the efficiency of viral endocytosis and that hydroxytyrosol has antiviral properties. Bioinformatic docking studies showed that alpha-cyclodextrin and hydroxytyrosol, alone or in combination, interact with the viral spike protein and its host cell receptor ACE2, thereby potentially influencing the endocytosis process. Conclusions: Hydroxytyrosol and alpha-cyclodextrin can be useful against the spread of SARS-CoV-2.
... In this study, the SARS-CoV-2 inactivating activities of HIDROX and HT, especially the superiority of HIDROX to pure HT, was shown in vitro (Figures 1 and 2). We previously showed that HT inactivated enveloped viruses, namely, IAV and Newcastle disease virus, and not non-enveloped viruses, namely, bovine rotavirus and fowl adenovirus [17]. In this report, the hemagglutination activity of HA protein and neuraminidase activity of NA protein, expressed on the surface of IAV, seemed unaffected by HT, and the impact of HT on viral structural proteins was unclear. ...
... To identify the binding sites of HT to SARS-CoV-2 structural proteins, computational docking analysis will be useful in the future. Our previous study revealed the possibility that the viral envelope was the site of action of HT because nonenveloped viruses are unaffected by HT [17]. Moreover, HIDROX or HT treatment disrupts the SARS-CoV-2 genome ( Figure 5). ...
Article
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally. Although measures to control SARS-CoV-2, namely, vaccination, medication, and chemical disinfectants are being investigated, there is an increase in the demand for auxiliary antiviral approaches using natural compounds. Here we have focused on hydroxytyrosol (HT)-rich aqueous olive pulp extract (HIDROX®) and evaluated its SARS-CoV-2-inactivating activity in vitro. We showed that the HIDROX solution exhibits time- and concentration-dependent SARS-CoV-2-inactivating activities, and that HIDROX has more potent virucidal activity than pure HT. The evaluation of the mechanism of action suggested that both HIDROX and HT induced structural changes in SARS-CoV-2, which changed the molecular weight of the spike proteins. Even though the spike protein is highly glycosylated, this change was induced regardless of the glycosylation status. In addition, HIDROX or HT treatment disrupted the viral genome. Moreover, the HIDROX-containing cream applied on film showed time- and concentration-dependent SARS-CoV-2-inactivating activities. Thus, the HIDROX-containing cream can be applied topically as an antiviral hand cream. Our findings suggest that HIDROX contributes to improving SARS-CoV-2 control measures.
... Hydroxytyrosol has broad-spectrum antiviral activity, especially against enveloped viruses, like influenza virus, HIV and coronaviruses. For instance, it may induce morphological changes that reduce influenza virus infectivity 9 . The exact mechanism of action is unclear but seems to require the presence of the envelope. ...
... These results further sustain our preliminary studies that suggested reduced risk of contracting the infection and reduced duration of symptoms, probably due to fewer membrane lipid rafts containing ACE2 associated with α-cyclodextrin treatment, while in addition hydroxytyrosol may have direct antiviral effects 9,18,19 . ...
Article
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Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new coronavirus responsible for the current pandemic of coronavirus disease 2019 (COVID-19). This virus attacks cells of the airway epithelium by binding transmembrane angiotensin-converting enzyme 2 (ACE2). Hydroxytyrosol has anti-viral properties. Alpha-cyclodextrin can deplete sphingolipids and phospholipids from cell membranes. The aim of the present experimental study was to evaluate the efficacy of α-cyclodextrin and hydroxytyrosol in improving defenses against SARS-CoV-2 infection in in vitro cell models and humans. Patients and methods: For in vitro experiments on Vero E6 cells, RNA for RT-qPCR analysis was extracted from Caco2 and human fibroblast cell lines. For study in humans, the treatment group consisted of 149 healthy volunteers in Northern Cyprus, considered at higher risk of SARS-CoV-2 infection than the general population. The volunteers used nasal spray containing α-cyclodextrin and hydroxytyrosol for 4 weeks. The control group consisted of 76 healthy volunteers who did not use the spray. Results: RT-qPCR experiments on targeted genes involved in endocytosis showed a reduction in gene expression, whereas cytotoxicity and cytoprotective tests showed that the compounds exerted a protective effect against SARS-CoV-2 infection at non-cytotoxic concentrations. None of the volunteers became positive to SARS-CoV-2 RT-qPCR assay during the 30 days of treatment. Conclusions: Treatment with α-cyclodextrin and hydroxytyrosol nasal spray improved defenses against SARS-CoV-2 infection and reduced synthesis of viral particles.
... Oleuropein, the main phenolic compound present at olive, is formed by esterification of hydroxytyrosol and a glycosylated monoterpene, the elenolic acid (EA). 16,20 It is hypothesised that the real antimicrobial effect of oleuropein would be due to its components hydroxytyrosol 23 and EA, although there are still no studies carried out with EA obtained from natural sources. Early research with calcium elenolate salts revealed its antiviral activity, including influenza and parainfluenza, in vitro and in animal models. ...
... The proposed mechanism of inhibition in hydroxytyrosol would be related to abnormalities provoked by the substance in the surface of the virion envelope. 23 The anti-influenza effect of Isenolic ® can be attributed to its EA content, because the extract showed an EA dosedependent inhibition. The role of several elenolic derivates against the influenza viruses is known since decades, especially in works done with the calcium salt of EA. ...
Article
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Seasonal flu is caused by influenza infection, a virus that spreads easily in human population with periodical epidemic outbreaks. The high mutational rate of influenza viruses leads to the emergence of strains resistant to the current treatments. Due to that, scientific research is focusing on the development of new anti-influenza agents as alternative or complementary treatments. Olive tree ( Olea europaea L.) has been a source of ancestral remedies due to its antimicrobial activity. Thus, the aim of this study was to test the anti-influenza activity of a standardized olive leaf extract rich in elenolic acid (EA), Isenolic ® , compared with oseltamivir. Isenolic ® extract was characterized by High Performance Liquid Chromatography (HPLC)-Mass Spectrometry and its content in EA was determined by HPLC. Cytotoxicity, viral neuraminidase inhibitor activity and cell viability protection against influenza infection of Isenolic ® were tested in vitro using sialic acid overexpressing Madin-Darby Canine Kidney cells. Isenolic ® formulations showed a 4% and 8% dry basis. Oseltamivir and Isenolic ® extracts showed anti-influenza activity. The 8% Isenolic ® formulation showed a dose-dependent neuraminidase inhibitor activity higher than the 4% formulation, and preserved cell viability under viral infection. Thus, Isenolic ® become a promising natural alternative to existing influenza treatments.
... Hydroxytyrosol (HXT) was known to inhibit influenza-A virus sub types H5N1, H1N1, H9N2 and H3N2. Kentaro Yamada et al. (2009), studied the antiviral effects of HXT using influenza-A virus, New castle Disease Virus (NDV), Bovine rotavirus (BRV) and fowl adenovirus (FAV)[100]. HXT was effective against the enveloped viruses and found ineffective against non-enveloped viruses. ...
Article
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can affect replication or protease activity of coronavirus. The clinical testing and regulatory approvals for these drugs will take time. However, currently there is an urgent requirement of treatment strategies which are safe, effective and can be implemented through readily available products in market. Many plant derived products rich in secondary metabolites having potential health benefits and antimicrobial properties. The olive plant leaf extracts and olive oil are rich sources of secondary metabolites such as phenols (oleuropein and hydroxytyrosol) and terpenoids (oleanolic, maslinic and ursolic acid). These compounds have been used as an effective antiviral agents in the past. The phenolics affect the virus attachment and replication. Whereas, the terpenoids mainly affects the membrane fluidity of the virus. In the recent molecular docking studies, it was found that, these compounds effectively bound to Mpro and 3CL pro protease sites of SARS-CoV-2 and were predicted to affect the replication of the SARS-CoV-2. Apart from antiviral properties, these bioactive compounds possess various other pharmacological properties such as anti-inflammatory, anti-modulatory, anti-thrombotic and anti-oxidative. The olive oil is consumed as a source of dietary fat and is the secret behind the good health in Mediterranean people. The consumption of olive oil is safe and is believed to increase the immunity against various infectious microbes. Hence olive products can be explored in management of COVID-19. In this review the various properties of phenolic and terpenoid compounds found in olives were discussed in the context of COVID-19.
... For instance, it is able to reduce HIV replication (6), and fusion in vitro (4,7,8). HT is also able to induce morphological changes that reduce influenza virus infectivity (9). It also enhances anti-inflammatory effects by decreasing the levels of pro-inflammatory cytokines IL-6 and TNF-α, as observed in animal models (10). ...
Article
Background and aim of the work: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current pandemics of coronavirus disease. This virus is able to attack the cells of the airway epithelium by binding to the transmembrane angiotensin I converting enzyme 2 (ACE2). We developed an oral spray that could inhibit the SARS-CoV-2 endocytosis. The spray contains hydroxytyrosol for its anti-viral, anti-inflammatory and anti-oxidant properties, and α-cyclodextrin for its ability to deplete sphingolipids, that form the lipid rafts where ACE2 localizes. The aim of the present pilot multi-centric open non-controlled observational study was to evaluate the safety profile of the "Endovir Stop" spray. Methods: An MTT test was performed to evaluate cytotoxicity of the spray in two human cell lines. An oxygen radical absorbance capacity assay was performed to evaluate the antioxidant capacity of the spray. The spray was also tested on 87 healthy subjects on a voluntary basis. Results: The MTT test revealed that the spray is not cytotoxic. The ORAC assay showed a good antioxidant capacity for the spray. Endovir Stop tested on healthy volunteers showed the total absence of side effects and drug interactions during the treatment. Conclusions: We demonstrated that Endovir Stop spray is safe. The next step would be the administration of the efficacy of the spray by testing it to a wider range of people and see whether there is a reduced infection rate of SARS-CoV-2 in the treated subjects than in the non-treated individuals.
... Polyphenols contribute significantly to antioxidant defense of animals by increasing the antioxidant levels of endogenous molecules and enzymes, while enhancing the immune system (21). In particular, polyphenols from OMW have antioxidant properties which are related to prevention of diseases caused by oxidative stress (22)(23)(24)(25). According to Paiva-Martins et al. (26), polyphenols of olive oil protected human erythrocytes from oxidative damage. ...
Article
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Background/aim: The aim of the present study was to investigate the antioxidant effects of a feed supplemented with polyphenolic additives from olive mill wastewater (OMW) on lambs. Materials and methods: Lambs received breast milk until the postnatal period, and then they were divided into two groups and received control and OMW feed for 55 days. Redox biomarkers were measured in blood and tissues at days 15, 42 and 70 after feeding. Results: Feed supplemented with OMW reduced thiobarbituric acid reactive species and protein carbonyls and increased total antioxidant capacity, glutathione and catalase activity in both blood and tissues. Conclusion: The administration of OMW-containing feed reinforced the antioxidant defense of lambs, which may improve their wellbeing and productivity. Additionally, this exploitation of OMW may solve problems of environmental pollution in areas with olive oil industries.
... 近来人们发现羟基酪醇对多种 流感亚型, 如H1N1、H3N2、H5N1及H9N2等, 也具有 抑制作用. 其作用机制可能是通过影响病毒的形态而 破坏病毒的结构, 达到干扰病毒进入细胞的目的 [51] . ...
... HTyr was identified as a unique class of HIV-1 inhibitors that prevent HIV from entering into the host cell and binding the catalytic site of the HIV-1, with both, viral entry and integration inhibited [91]. Furthermore, it was reported that HTyr inactivated influenza A viruses, suggesting that the mechanism of the antiviral effect of HTyr might require the presence of a viral envelope [92]. ...
Article
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The Mediterranean diet and olive oil as its quintessential part are almost synonymous with a healthy way of eating and living nowadays. This kind of diet has been highly appreciated and is widely recognized for being associated with many favorable effects, such as reduced incidence of different chronic diseases and prolonged longevity. Although olive oil polyphenols present a minor fraction in the composition of olive oil, they seem to be of great importance when it comes to the health benefits, and interest in their biological and potential therapeutic effects is huge. There is a growing body of in vitro and in vivo studies, as well as intervention-based clinical trials, revealing new aspects of already known and many new, previously unknown activities and health effects of these compounds. This review summarizes recent findings regarding biological activities, metabolism and bioavailability of the major olive oil phenolic compounds—hydroxytyrosol, tyrosol, oleuropein, oleocanthal and oleacein—the most important being their antiatherogenic, cardioprotective, anticancer, neuroprotective and endocrine effects. The evidence presented in the review concludes that these phenolic compounds have great pharmacological potential, however, further studies are still required.
... There are many factors that influencing the EOs mode of action, which should be taken in consideration when antiviral activity of plant antimicrobials is examined. One of such factors is the difference between enveloped and non-enveloped viruses, because the observed antiviral effect has usually been greater for enveloped viruses (Yamada et al., 2009;Siddiqui et al., 1996). In majority of the studies dealing with antiviral mode of action, the focus has been on either the inhibition of viral adsorption to host cells or examination of the plant antimicrobials effectiveness against intracellular virus multiplication (Gilling et al., 2014). ...
Article
Eucalyptus has become one of the world's most widely planted genera and E. camaldulensis (The River Red Gum) is a plantation species in many parts of the world. The plant traditional medical application indicates great antimicrobial properties, so E. camaldulensis essential oils and plant extracts have been widely examined. Essential oil of E. camaldulensis is active against many Gram positive (0.07-1.1%) and Gram negative bacteria (0.01-3.2%). The antibacterial effect is confirmed for bark and leaf extracts (conc. from 0.08 μg/mL to 200 mg/mL), with significant variations depending on extraction procedure. Eucalyptus camaldulensis essential oil and extracts are among the most active against bacteria when compared with those from other species of genus Eucalyptus. The most fungal model organisms are sensitive to 0.125-1.0% of E. camaldulensis essential oil. The extracts are active against C. albicans (0.2-200 mg/mL leaf extracts and 0.5 mg/mL bark extracts), and against various dermatophytes. Of particular importance is considerable the extracts' antiviral activity against animal and human viruses (0.1-50 μg/mL). Although the antiprotozoal activity of E. camaldulensis essential oil and extracts is in the order of magnitude of concentration several hundred mg/mL, it is considerable when taking into account current therapy cost, toxicity, and protozoal growing resistance. Some studies show that essential oils' and extracts' antimicrobial activity can be further potentiated in combinations with antibiotics (beta-lactams, fluorochinolones, aminoglycosides, polymyxins), antivirals (acyclovir), and extracts of other plants (e.g. Annona senegalensis; Psidium guajava). The present data confirm the river red gum considerable antimicrobial properties, which should be further examined with particular attention to the mechanisms of antimicrobial activity.
... медицина [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. В табл.2 приведен перечень полифенолов-антиоксидантов, для которых подтверждены их антивирусное действие, их структура и пищевые источники [34][35][36][37][38][39][40][41][42][43][44][45][46][47]. ...
... Hydroxytyrosol and tyrosol are natural phenolic antioxidants present in olives (Cabrera-Bañegil et al., 2017), leaves (Benavente-García et al., 2000), stems and roots (Ortega-García and Peragón, 2010), olive mill wastewater (De Marco et al., 2007) and olive oil (Ben Brahim et al., 2017). They have shown a various biological activity such as antiviral (Yamada et al., 2009), antibacterial (Capasso et al., 1995), fungicidal (Yangui et al., 2010), but especially are considered as powerful antioxidant agents (De Marco et al., 2007;Obied et al., 2005;Pérez-Bonilla et al., 2014). The results presented in this study showed that the trend of root tyrosol and hydroxytyrosol concentrations was different from that of oleuropein. ...
Article
Polyphenols are constituents of all higher plants. However, their biosynthesis is often induced when plants are exposed to abiotic stresses, such as drought. The aim of the present work was to determine the phenolic status in the roots of olive trees grown under water deficit conditions. The results revealed that roots of water-stressed plants had a higher content of total phenols. The main compound detected in well-watered olive tree roots was verbascoside. Oleuropein was established as the predominant phenolic compound of water-stressed plants. The oleuropein/verbascoside ratio varied between 0.31 and 6.02 in well-watered and water-stressed plants respectively, which could be a useful indicator of drought tolerance in olive trees. Furthermore, this study is the first to provide experimental evidence showing that luteolin-7-rutinoside, luteolin-7-glucoside and apigenin-7-glucoside were the dominant flavonoid glucosides in olive tree roots and showed the most significant variations under water stress.
... Many studies have underlined its biological activities and among them stands out the antioxidant, anti-inflammatory, antiatherogenic, and antiviral ones (Lammi et al., 2020). Hydroxytyrosol is also efficacious in the treatment of some viral diseases, such as influenza virus (Yamada et al., 2009) and HIV (Bedoya et al., 2016) (Bedoya et al., 2016). In addition, hydroxytyrosol is active against pulmonary fibrosis in rats (Liu et al., 2015) and in reducing the oxidative stress related to the respiratory burst of neutrophils (Visioli et al., 1998). ...
Article
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SARS‐CoV‐2 (previously 2019‐nCoV), the pathogenic agent of COVID‐19 disease, started to expand from Wuhan, China, on December 2019 and in 2 months, it spread worldwide giving origin to a pandemic. COVID‐19 has a stronger transmission capacity by inhalation of infectious aerosols and after an incubation time of 3–14 days, it may be responsible for diseases ranging from the asymptomatic to fatal consequences. COVID‐19 has emerged as a multifaceted, multisystem, multi‐organ disorder, which produces its pathogenic effects through a quite ubiquitous target at the level of multiple organs and in which oxidative stress and inflammatory process play relevant roles. Thus, besides the development of a pharmacological therapy, in the field of alternative and coadjutant therapeutic, the use of dietary supplements or nutraceuticals for the prevention or treatment of SARS‐CoV‐2 infection may be a useful strategy. Herein, we specifically comment on some literature evidences, which link the food‐derived antioxidants and metal‐chelating agents with treatment and prevention of oxidative stress and inflammation that play a key role in the progression of COVID‐19. Practical applications Oxidative stress and inflammation are key factors increasing COVID‐19 severity especially in the presence of chronic diseases associated with the antioxidant system fragility. These evidences support the recommendation of antioxidants supplementation as useful strategies against COVID‐19. In light with these observations, herein, a comment which describes the major antioxidants and metal‐chelating agents from food sources that might be useful for the treatment and prevention of oxidative stress and inflammation during COVID‐19.
... Polyphenols, in particular, have been found to have a strong antimicrobial and antiviral activity (Chiow et al., 2016;de Oliveira et al., 2015;Jassim and Naji, 2003;Mukhtar et al., 2008;Song et al., 2005;Zhang et al., 2020;Zhong et al., 2012). Oleuropein (Omar, 2010), for example, and its derivatives (tyrosol and hydroxytyrosol) (Yamada et al., 2009) (extracted from olive leaves, Olea europaea) and eugenol (extracted from cloves, Eugenia caryophyllus L.) (Hume, 1986) have a structure similar to the conserved amino acids of the SARS− COV-19 virus S protein involved in receptor interaction (Sivanesam and Andersen, 2019). ...
Article
Clove buds is a spice of relevance in food, traditional medicine, pharmaceutics and cosmetics and, among the spices, they have the highest content of total polyphenols with exceptional antiviral and antimicrobial properties. Various approaches have been reported for the isolation of essential oil from clove buds. Nonetheless, the qualitative and quantitative analysis of hydrosoluble polyphenols and solid residues simultaneously yielded during the extraction process has not been explored yet. This work is focused on the analysis of some variables effect on yield and composition of the clove buds essential oils on a green microwave assisted extraction, and the characterization and quantification of the different compounds obtained from the extraction process. A versatile coaxial dipole antenna, to directly apply the electromagnetic energy inside the extraction medium, was used to thermally activate the hydrodistillation. The composition profiles of clove buds essential oil and hydrosoluble polyphenols obtained during in-situ microwave assisted extraction (IMWAE) were analysed and quantified by head space gas chromatography mass spectrometry (HS-GC-MS) and liquid chromatography with UV/visible diode array/fluorescence detector (HPLC-DAD-FD). The solid residue was characterized by Fourier Transform Infrared (FTIR) spectroscopy and its composition in term of lignin, cellulose and hemicellulose was predicted. The green IMWAE process was compared with the conventional hydrodistillation (CH) in terms of yield and quality of isolated products. Thermogravimetry coupled to FTIR analyses of the evolved gases from the solid residue evidenced that the solid residue obtained from IMWAE of clove buds is richer in cellulose-hemicellulose than the residue obtained from CH. This can be because of microwaves that allow to remove a higher amount of phenolic compounds/lignin oligomers. The enthalpy of combustion values (Δ c H) (kJ/g) of IMWAE and CH residues were determined by calorimetric combustion and were compared with the-Δ c H (kJ/g) values calculated using the hemicellulose, cellulose and lignin compositions predicted by partial least square chemometrics. The Δ c H highlighted the energetic features of solid residues from IMWAE and CH for their potential uses as alternative biomass for fuel production and here firstly reported for this kind of biomass. The extraction approach here presented is environmentally friendly, highly flexible, easily controllable, time saving, and enables to break the scale-up barrier in microwave assisted industrial processes aimed to valorise aromatic herbs and eventually to exploit vegetable wasting materials. This leads to a lowering of production costs and, therefore, of the market price of isolated extracts from aromatic herbs.
... A viral envelope is required for the antiviral activity of hydroxytyrosol. Oleuropein and hydroxytyrosol inhibit the fusion of viruses with cell membranes (39). Since SARS-CoV-2 is an enveloped virus with spike glycoproteins, hydroxytyrosol may inhibit its endocytosis. ...
Article
Background and aim: The recent COVID-19 pandemic caused by SARS-CoV-2 affected more than six million people and caused thousands of deaths. The lack of effective drugs or vaccines against SARS-CoV-2 further worsened the situation. This review is focused on the identification of molecules that may inhibit viral entry into host cells by endocytosis. Methods: We performed the literature search for these natural compounds in the articles indexed in PubMed. Results: Natural products against viral infections have been gaining importance in recent years. Specific natural compounds like phytosterols, polyphenols, flavonoids, citrus, galangal, curcuma and hydroxytyrosol are being analyzed to understand whether they could inhibit SARS-CoV-2. Conclusions: We reviewed natural compounds with potential antiviral activity against SARS-CoV-2 that could be used as a treatment for COVID-19.
... In particular, HT and oleuropein bind to gp41, a HIV-1 envelope protein, causing a conformational change in the glycoprotein, with consequent inhibition of viral entry into the target cells [122,124,125]. HT also seems to act on a molecule on the viral envelope of influenza virus, disrupting the structure [126]. In this regard, HT has been proposed as an agent able to interfere with the attachment of SARS-CoV2 to host cells, thus, acting as a preventive remedy in patients at high risk of infection [127]. ...
Article
Background and Objectives Dietary habits strongly influence our health status, mostly, in terms of maintenance of the inflammatory/anti-inflammatory homeostasis. High fat and high sugar diets account for the development of a low-grade inflammation which is the pathogenic common denominator of various chronic disease. Severe Acute Respiratory Syndrome Coronavirus (SARS)-CoV2 (COVID-19) infection affects all ages and especially frail elderly people and a nutri-tional intervention seems to be crucial in the course of this pandemic. The present review describes the properties of some vegetal products and their derivatives, such as Lupin sp., garlic, salvia and extra virgin olive oil (EVOO) that can be exploit-ed for their beneficial effects, as preventive and/or nutritional treatment of coronavirus disease SARS-CoV2. Discussion Lupin, salvia, garlic and EVOO share overlapping properties, such as anti-oxidant, anti-inflammatory and anti-viral activities. Quite importantly, these products and their derivatives are able to recover the expression of angiotensin con-verting enzyme expression 2 on cell membrane, otherwise suppressed by COVID-19 binding and entry into cytoplasm. Conclusion Dietary administration of the above nutraceuticals or their extracts may play a preventive or nutritional role in the course of SARS-CoV2 infection, even including the effects of the lockdown and the condition of inflamm-ageing.
... The antioxidation protective benefits of OO, especially EVOO, which has a higher phenolic content [40] promotes its role for enhancing the immune system defence against viruses. Hydroxytyrosol antiviral mechanisms were showed through its inactivation effects on influenza A viruses, especially during the virus morphological changes, such as the presence of a viral envelope which is an integral membrane protein involved in several aspects of the virus life cycle including its assembly, budding, and pathogenesis [72]. The mechanisms of which OO nutraceuticals protect against viral infections have often focused on the hydroxytyrosol preventative effects on HIV from entering the host cell and binding the catalytic site of the HIV-1, and its inhibitory effect on both viral entry and integration [73]. ...
Article
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Novel coronavirus (COVID-19) is causing global mortality and lockdown burdens. A compromised immune system is a known risk factor for all viral influenza infections. Functional foods optimize the immune system capacity to prevent and control pathogenic viral infections, while physical activity augments such protective benefits. Exercise enhances innate and adaptive immune systems through acute, transient, and long-term adaptations to physical activity in a dose-response relationship. Functional foods prevention of non-communicable disease can be translated into protecting against respiratory viral infections and COVID-19. Functional foods and nutraceuticals within popular diets contain immune-boosting nutraceuticals, polyphenols, terpenoids, flavonoids, alkaloids, sterols, pigments, unsaturated fatty-acids, micronutrient vitamins and minerals, including vitamin A, B6, B12, C, D, E, and folate, and trace elements, including zinc, iron, selenium, magnesium, and copper. Foods with antiviral properties include fruits, vegetables, fermented foods and probiotics, olive oil, fish, nuts and seeds, herbs, roots, fungi, amino acids, peptides, and cyclotides. Regular moderate exercise may contribute to reduce viral risk and enhance sleep quality during quarantine, in combination with appropriate dietary habits and functional foods. Lifestyle and appropriate nutrition with functional compounds may offer further antiviral approaches for public health.
... The above-mentioned suggests that hydroxytyrosol may be used in the treatment of infections produced by several bacterial sources in the context of respiratory tract infections. Hydroxytyrosol has also been found to be effective in the treatment of some viral diseases, such as influenza virus(Yamada et al., 2009) and HIV (Bedoya et al., 2016). Finally,Liu et al. have shown that hydroxytyrosol is effective against pulmonary fibrosis in rats(Liu et al., 2015). ...
Article
The repositioning of therapeutic agents already approved by the regulatory agencies for the use of drugs is very interesting due to the immediacy of their use; similarly, the possibility of using molecules derived from foods, whether nutrients or not, is of great importance, also because of their immediate therapeutic applicability. Candidates for these natural therapies against COVID-19 should show certain effects, such as restoring mitochondrial function and cellular redox balance. This would allow reducing the susceptibility of risk groups and the cascade of events after SARS-CoV-2 infection, responsible for the clinical picture, triggered by the imbalance towards oxidation, inflammation, and cytokine storm. Possible strategies to follow through the use of substances of food origin would include: a) the promotion of mitophagy to remove dysfunctional mitochondria originating from free radicals, proton imbalance and virus evasion of the immune system; b) the administration of transition metals whose redox activity would lead to their own oxidation and the consequent generation of a reduced environment, which would normalize the oxidative state and the intracellular pH; c) the administration of molecules with demonstrated antioxidant capacity; d) the administration of compounds with anti-inflammatory and vasodilatory activity; e) the administration of immunomodulatory compounds.
... Hydroxytyrosol has a broad-spectrum antiviral activity, especially against enveloped viruses like influenza virus, HIV or coronaviruses. For instance, hydroxytyrosol is able to induce morphological changes that reduce influenza virus infectivity (8). It also enhances anti-inflammatory effects by decreasing the levels of pro-inflammatory cytokines IL-6 and TNF-α, as observed in animal models (9). ...
Article
Background and aim of the work: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current pandemics. This virus attacks the cells by binding to the transmembrane angiotensin I converting enzyme 2. In this study, we experimented a food supplement containing alpha-cyclodextrin and hydroxytyrosol for the improvement of the defenses against the SARS-CoV-2. Hydroxytyrosol has anti-viral properties and is able to reduce the serum lipids in mice. α-cyclodextrin has the ability to deplete sphingolipids and phospholipids from the cellular membranes. The aim of the present preliminary open non-controlled interventional study was to evaluate the efficacy of alpha-cyclodextrin and hydroxytyrosol in improving defenses against SARS-CoV-2. Methods: Fifty healthy volunteers at a higher risk of SARS-CoV-2 infection from Northern Cyprus and six positive individuals for SARS-CoV-2 were enrolled in this study. The in silico prediction was performed using D3DOCKING to evaluate the interactions of hydroxytyrosol and alpha-cyclodextrin with proteins involved in the SARS-CoV-2 endocytosis. Results: The 50 volunteers did not become positive in 15 days for SARS-CoV-2 after the administration of the compound for two weeks, despite they were at higher risk of infection than the general population. Interestingly, in the cohort of six positive patients, two patients were administered the spray and became negative after five days, despite the viral load was higher in the treated subjects than the untreated patients who became negative after ten days. In addition, we identified possible interactions among hydroxytyrosol and alpha-cyclodextrin with the protein Spike and the human proteins ACE2 and TMPRSS2. Conclusions: We reported on the results of the possible role of alpha-cyclodextrin and hydroxytyrosol in improving defenses against SARS-CoV-2. The next step will be the administration of the compound to a larger cohort in a controlled study to confirm the reduction of the infection rate of SARS-CoV-2 in the treated subjects.
... 23 The higher level of oxidation inhibition was reached using 100 ppm of HT ( Figure 1). Exerting neuroprotective, anti-inflammatory, anticancer, and even antiviral (against several influenza A viruses) 24 activities, hydroxytyrosol, which is abundant in O. europaea, was recently found to be "the most actively investigated natural phenol". 25 The compound has limited antibacterial activity, 26 but its great pharmacological potential is widely recognized. ...
Article
Thanks to the pioneering studies of Østerud and co-workers, it is now increasingly understood that natural polyphenols present in marine oils play an essential role in protecting omega-3 lipids from oxidation and autoxidation, ensuring that no proinflammatory products are formed after intake as often happens with assumption of refined omega-3 concentrates. Strong antioxidants exerting multiple biological functions, olive biophenols are ideally suited to functionalize marine oils, creating a synergy that has the potential to improve public health across the world. This study identifies suitable avenues for advancing the sustainable production of health-beneficial formulations based on newly obtained natural marine oils and olive phenolic extracts. Important educational outcomes conclude the study.
... In addition, frHibis also contains abundant bioactive compounds such as phenolic compounds (Da-Costa-Rocha et al. 2014). Several studies reported that polyphenol-rich plant extracts and plant-derived phenolic compounds have anti-IAV activities (Droebner et al. 2007;Kim et al. 2013;Yamada et al. 2009). These phenolic compounds in frHibis may also contribute to antiviral activity. ...
Article
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Influenza A virus (IAV) infection is perennially one of the leading causes of death worldwide. Effective therapy and vaccination are needed to control viral expansion. However, current anti-IAV drugs risk inducing drug-resistant virus emergence. Although intranasal administration of whole inactivated virus vaccine can induce efficient protective immunity, formalin and β-propiolactone are the currently used and harmful inactivating agents. Here, we analyzed the antiviral activity of hibiscus (Hibiscus sabdariffa L.) tea extract against human IAV and evaluated its potential as a novel anti-IAV drug and a safe inactivating agent for whole inactivated vaccine. The in vitro study revealed that the pH of hibiscus tea extract is acidic, and its rapid and potent antiviral activity relied largely on the acidic pH. Furthermore, the mouse study showed that the acidic extract was not effective for either therapeutic or vaccination purposes. However, hibiscus tea extract and protocatechuic acid, one of the major components of the extract, showed not only potent acid-dependent antiviral activity but also weak low-pH-independent activity. The low-pH-independent activity did not affect the conformation of immunodominant hemagglutinin protein. Although this low-pH-independent activity is very limited, it may be suitable for the application to medication and vaccination because this activity is not affected by the neutral blood environment and does not lose antigenicity of hemagglutinin. Further study of the low-pH-independent antiviral mechanism and attempts to enhance the antiviral activity may establish a novel anti-IAV therapy and vaccination strategy.
... A specific olive oil polyphenol, hydroxytyrosol [(3, 4-dihydroxyphenyl) ethanol, 26], is an active compound. It possesses antiviral activity against influenza A virus [131]. ...
Article
Full-text available
Background: Phenolic compounds are a class of the most widely distributed secondary metabolites in plants. They may function as pollination, pigment constituents and protection against UV radiation and predation for plants. Plant phenols have been studied for hundreds of years, and have acted as the major class of compounds that show great activity against various viruses such as herpes simplex, Epstein-Barr virus, equid herpesvirus, hepatitis B virus, human immunodeficiency virus, respiratory syncytial and canine distemper viruses. Because of the extensive antiviral activities, phenolic compounds have been widely investigated both chemically and biologically. The distribution of hydroxyl groups and ester group accounts for different antiviral activities of phenolic compounds, and research of these compounds has revealed that phenols have great potential for the development as therapeutic agents against various viruses. As a result, dozens of phenols in functional foods have been discovered to display antiviral activity. Objective: This review emphasizes structure classification and antiviral activities of plant phenolic compounds, which are expected to provide guides for rational design of antiviral drugs.
... HT is considered the most powerful antioxidant after gallic acid. It has been most studied and used in food, cosmetic, and pharmaceutical industries [88] after being demonstrated that HT produces a wide range of biological properties besides antioxidant such as hepatoprotective [89], cytoprotective [90], neuroprotective [91], cardioprotective [92], anti-inflammatory [93], antiviral [94], anticancer [85], and anti-obesity effect [95]. Some studies affirm that the composition of olive leaves extracts rich in several phenols and flavonoids and that it varies with the harvesting season, the leaves maturity, storage conditions, and extraction method [96]. ...
Article
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Over the last years, different nanomaterials have been investigated to design highly selective and sensitive sensors, reaching nano/picomolar concentrations of biomolecules, which is crucial for medical sciences and the healthcare industry in order to assess physiological and metabolic parameters. The discovery of graphene (G) has unexpectedly impulsed research on developing cost-effective electrode materials owed to its unique physical and chemical properties, including high specific surface area, elevated carrier mobility, exceptional electrical and thermal conductivity, strong stiffness and strength combined with flexibility and optical transparency. G and its derivatives, including graphene oxide (GO) and reduced graphene oxide (rGO), are becoming an important class of nanomaterials in the area of optical and electrochemical sensors. The presence of oxygenated functional groups makes GO nanosheets amphiphilic, facilitating chemical functionalization. G-based nanomaterials can be easily combined with different types of inorganic nanoparticles, including metals and metal oxides, quantum dots, organic polymers, and biomolecules, to yield a wide range of nanocomposites with enhanced sensitivity for sensor applications. This review provides an overview of recent research on G-based nanocomposites for the detection of bioactive compounds, providing insights on the unique advantages offered by G and its derivatives. Their synthesis process, functionalization routes, and main properties are summarized, and the main challenges are also discussed. The antioxidants selected for this review are melatonin, gallic acid, tannic acid, resveratrol, oleuropein, hydroxytyrosol, tocopherol, ascorbic acid, and curcumin. They were chosen owed to their beneficial properties for human health, including antibiotic, antiviral, cardiovascular protector, anticancer, anti-inflammatory, cytoprotective, neuroprotective, antiageing, antidegenerative, and antiallergic capacity. The sensitivity and selectivity of G-based electrochemical and fluorescent sensors are also examined. Finally, the future outlook for the development of G-based sensors for this type of biocompounds is outlined.
... The combination of vitamin C, curcumin, and glycyrrhizic acid stimulates interferon production and modulates the immune response, counteracting SARS-CoV-2 infections ). Hydroxytyrosol, a phenolic compound present in extra virgin olive oil, shows antioxidant, anti-inflammatory, antiatherogenic and antiviral activities (Clodoveo et al. 2015;Cicero et al. 2018;Lammi et al. 2020), also it is effective in treating some viral diseases such as influenza virus (Yamada et al. 2009). Scientific studies suggest that low carotenoid levels are associated with important conditions of oxidative stress and inflammation (Walston et al. 2006). ...
Article
Viral diseases have always played an important role in public and individual health. Since December 2019, the world is facing a pandemic of SARS-CoV-2, a coronavirus that results in a syndrome known as COVID-19. Several studies were conducted to implement antiviral drug therapy, until the arrival of SARS-CoV-2 vaccines. Numerous scientific investigations have considered some nutraceuticals as an additional treatment of COVID-19 patients to improve their clinical picture. In this review, we would like to emphasize the studies conducted to date about this issue and try to understand whether the use of nutraceuticals as a supplementary therapy to COVID-19 may be a valid and viable avenue. Based on the results obtained so far, quercetin, astaxanthin, luteolin, glycyrrhizin, lactoferrin, hesperidin and curcumin have shown encouraging data suggesting their use to prevent and counteract the symptoms of this pandemic infection.
... For each concentration, 12 wells were infected with a 50 µl viral suspension and then incubated at 37˚C under 5% CO 2 for 168 h. The virus titer [reported as 50% tissue culture infectious doses (TCID 50 /ml)] was calculated using the Behrens-Karber method (16). ...
Article
Sophocarpine (SCA) is a bioactive alkaloid present in Sophoraflavescens Ait. The present study demonstrated that SCA inhibited enterovirus 71 (EV71) infection in Vero cells. The results indicated that the 50% cytotoxicity concentration of SCA for Vero cells was 1,346 μg/ml, and the 50% inhibi­tion concentration of SCA against EV71 was 350 μg/ml. SCA produced a marked inhibitory effect against EV71 when the Vero cells were treated with SCA prior to infection with the virus. Additionally, SCA was effective against EV71 when the Vero cells were infected with EV71 (100×TCID50) that had been treated with SCA for 2 h, and was effective when the Vero cells were infected with EV71 (100×TCID50) at 37˚C under 5% CO2 for 2 h prior to treatment with SCA for 2 h. SCA was demonstrated to inhibit the attachment and penetration of EV71 and was more effective at inhibiting attachment. The assay additionally verified that SCA suppressed the replication of viral genomic RNA and indicated that SCA may inhibit EV71 infection in vitro.
... Hydroxytyrosol interacts with the plasma membrane, localizing itself at the level of the hydrophilic heads. This would confer protection against oxidative stress and modify the chemical-physical properties of the membrane [313]. The mechanism of the antiviral effect of HT suggested that the presence of a viral envelope was necessary. ...
Article
Full-text available
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the coronavirus disease of 2019 (COVID-19) that emerged in December 2019 in Wuhan, China, and rapidly spread worldwide, with a daily increase in confirmed cases and infection-related deaths. The World Health Organization declared a pandemic on the 11th of March 2020. COVID-19 presents flu-like symptoms that become severe in high-risk medically compromised subjects. The aim of this study was to perform an updated overview of the treatments and adjuvant protocols for COVID-19. Methods: A systematic literature search of databases was performed (MEDLINE PubMed, Google Scholar, UpToDate, Embase, and Web of Science) using the keywords: "COVID-19", "2019-nCoV", "coronavirus" and "SARS-CoV-2" (date range: 1 January 2019 to 31st October 2020), focused on clinical features and treatments. Results: The main treatments retrieved were antivirals, antimalarials, convalescent plasma, immunomodulators, corticosteroids, anticoagulants, and mesenchymal stem cells. Most of the described treatments may provide benefits to COVID-19 subjects, but no one protocol has definitively proven its efficacy. Conclusions: While many efforts are being spent worldwide in research aimed at identifying early diagnostic methods and evidence-based effective treatments, mass vaccination is thought to be the best option against this disease in the near future.
... HT did not show any cytotoxic effect on MDCK cells; it affected H9N2 virus NP protein synthesis and suppressed mRNA synthesis at 24 h.p.i. Electron microscopic analysis detects the structural disruption of the H9N2 virus by HT [113]. ...
Article
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Background Influenza is an acute respiratory tract infection caused by the influenza virus. Vaccination and antiviral drugs are the two methods opted to control the disease. Besides their efficiency, they also cause adverse side effects. Hence, scientists turned their attention to powerful herbal medicines. This review put focus on various proven, scientifically validated anti-influenza compounds produced by the plants suggested for the production of newer drugs for the better treatment of influenza and its related antiviral diseases too. Main body In this review, fifty medicinal herb phytochemical constituents and their anti-influenza activities have been documented. Specifically, this review brings out the accurate and substantiates mechanisms of action of these constituents. This study categorizes the phytochemical constituents into primary and secondary metabolites which provide a source for synthesizing and developing new drugs. Conclusion This article provides a summary of the actions of the herbal constituents. Since the mechanisms of action of the components are elucidated, the pandemic situation arising due to influenza and similar antiviral diseases can be handled promisingly with greater efficiency. However, clinical trials are in great demand. The formulation of usage may be a single drug compound or multi-herbal combination. These, in turn, open up a new arena for the pharmaceutical industries to develop innovative drugs.
... Acta ScientificHydroxytyrosol (HXT) was known to inhibit influenza-A virussub types H5N1, H1N1, H9N2, and H3N2. Kentaro Yamada., et al.[33] studied the anti-viral effects of HXT using influenza-A virus, Bovine rotavirus (BRV), New Castle Disease Virus (NDV), and fowl adenovirus (FAV). In many studies, HXT was found ineffective against non-enveloped and effective against enveloped viruses. ...
... The therapeutic strategy for was also exhibited by the hesperidin, lepidine E class of polyphenols. Yamada et al. (2009) and Bedoya et al. (2016) have revealed the efficacy of hydroxytyrosol in the treatment of viral disease as influenza. ...
... HTyr has been reported to have antiatherogenic, cardioprotective [145,146], anticancer [147,148], neuroprotective [149,150], antimicrobial [151,152], anti-inflammatory, and antiplatelet properties [66,153]. It is released by OLE hydrolysis, which also gives rise to OLE aglycone and elenolic acid [154]. ...
Article
Full-text available
The treatment of tissue damage produced by physical, chemical, or mechanical agents involves considerable direct and indirect costs to health care systems. Wound healing involves a series of molecular and cellular events aimed at repairing the defect in tissue integrity. These events can be favored by various natural agents, including the polyphenols in extra virgin olive oil (EVOO). The objective of this study was to review data on the potential effects of different phenolic compounds that can also be found in EVOO on wound healing and closure. Results of in vitro and animal studies demonstrate that polyphenols from different plant species, also present in EVOO, participate in different aspects of wound healing, accelerating this process through their anti-inflammatory, antioxidant, and antimicrobial properties and their stimulation of angiogenic activities required for granulation tissue formation and wound re-epithelialization. These results indicate the potential usefulness of EVOO phenolic compounds for wound treatment, either alone or in combination with other therapies. Human studies are warranted to verify this proposition.
... Many previous studies have shown that many of these oils and their components have antibacterial and antiviral properties [6] and [7]. Oregano (Origanumvulgare) and clove (Syzygiumaromaticum) essential oils are very efficient towards many viruses especially enveloped viruses such as; Herpes simplex virus type 1 (HSV-1) and (Newcastle) virus, but on the contrary it is ineffective against non-enveloped viruses such as; poliovirus (type-1) and adenovirus (type-3) [8]. As well as, discovery research for antiviral activity does not parallel to discovery important oil method for an in vitro and in vivo study observing an avian virus that responsible of upper respiratory infections in chickens and other birds exhibited that a exclusive compound revealed virucidal activity and was very strong in controlling virus-linked bronchitis in small chickens [9]. ...
Article
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Virus disease is transmitted disease caused by recently discovered a group of viruses infecting respiratory tract, most of the infected people have major clinical signs such as; cough, sneezes, cold, fever and sore throat. The virus can be transmitted among people through the generated droplets when an infected person (coughing and exhales) or physical contact. Natural herbal remedies has been used for a long periods of ancient human history for different purposes. The desirable properties of herbal medicine are low toxicity and natural origin, as well as it is causes few side effects due to the use of additives and preservatives in a very small quantities and this made it a favorite as an alternative treatment. The current study shows the antiviral properties of natural herbal oils such as; Lavender, Peppermint, Cinnamon, Eucalyptus and Thyme oils for the purpose of treating Virus disease.
... Several other studies have also shown that oleuropein possesses antiviral properties against respiratory syncytial virus and para-influenza type 3 virus (Ma et al., 2001;Zhao et al. 2009) found that oleuropein isolated from Jasminum officinale L. blocked effectively HBsAg secretion in HepG2 2.2.15 cells in a dose-dependent manner which could present a potential new therapeutic agent for hepatitis B virus infection. Oleuropein and hydroxytyrosol isolated from olive leaf extracts were found to bind to the conserved hydrophobic pocket on the surface of the HIV-gp41 fusion domain exhibiting a dose-dependent inhibition of HIV-1 with EC 50 s of 66-58 nM and no detectable toxicity (Lee-Huang et al., 2007;Yamada et al. 2009) reported that hydroxytyrosol was able to inactivate Newcastle disease virus and influenza A viruses, including H1N1, H3N2, H5N1, and H9N2 subtypes. In vitro and in silico studies revealed that natural polyphenols could have a good impact on the body's immune system against the SARS-CoV-2 virus . ...
Article
The Mediterranean olive oil industries are producing annually a massive quantity of olive mill wastewater (OMWW). Unfortunately, the OMWW is released arbitrarily in the nature without any pretreatment. Thus, it exhibits a high toxicity against the whole natural ecosystem including, microorganisms, plants and animals. In order to eliminate or reduce its pollution, OMWW must be properly treated prior to its release in the nature. In this regard, different treatment methods have been developed by researchers, but some of them were costly and others were inappropriate. Thus, more efforts should be made to save the nature from this pollutant. In the light of that, the current work summaries the state of knowledge regarding the OMWW from a chemical, biological, nutraceutical point of view, and the treatment methods that were used to eliminate its risk of pollution.
... A viral envelope is required for the antiviral activity of hydroxytyrosol. Oleuropein and hydroxytyrosol inhibit the fusion of viruses with cell membranes (39). Since SARS-CoV-2 is an enveloped virus with spike glycoproteins, hydroxytyrosol may inhibit its endocytosis. ...
... Eugster et al. showed antiviral effect of phytosterols on HIV-1, human cytomegalovirus (HCMV) and herpes simplex virus (HSV). 29 It has been known that HT can disrupt H9N2 virus, 30 and also about oleic acid which is the main monounsaturated fatty acid of the olive and fig extract has antiviral activity on Semliki Forest virus. 31 Therefore, it seems that the inactivation of the antiviral components of olive and fig extracts may increase the immunogenicity of the extracts against avian influenza virus subtype H9N2. ...
Article
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In this study, we investigated the antiviral activity of Olea europaea (OLE) extracts against Newcastle disease virus (NDV), a highly infectious and economically important poultry virus. For this purpose, viral gene expressions of two structural proteins, matrix (M) and fusion (F) of NDV, were monitoring in chicken fibroblast cells and the impact on virus replication was analyzed using qRT-PCR. Additionally, the virus-restriction activities of IFN-β were analyzed by assessing the expression of viral and host genes. In vitro analysis of the NDV replication revealed that treatment of chicken cells with OLE significantly restricted the NDV replication as was measured by haemagglutination (HA) and titration (TCID50) assays in a pre-optimized OLE-mediated cytotoxicity levels (1000ug/ml). Correspondingly, pretreatment of chicken cells with exogenous IFN-β markedly down-regulated viral gene expression, and this regulation was higher than OLE-mediated virus replication. Furthermore, the impact of OLE on NDV was independent of the IFN-β and was confirmed using ELISA. Taken together, findings of this study propose the utilization of OLE as immunoprophylaxis and exploitation of this function to control the ND in poultry and pet birds.
Article
This review presents information from several studies that have demonstrated the antiviral activity of extracts ( Andrographis paniculata, Artemisia annua, Artemisia afra, Cannabis sativa, Curcuma longa, Echinacea purpurea, Olea europaea, Piper nigrum, and Punica granatum) and phytocompounds derived from medicinal plants (artemisinins, glycyrrhizin, and phenolic compounds) against SARS-CoV-2. A brief background of the plant products studied, the methodology used to evaluate the antiviral activity, the main findings from the research, and the possible mechanisms of action are presented. These plant products have been shown to impede the adsorption of SARS-CoV-2 to the host cell, and prevent multiplication of the virus post its entry into the host cell. In addition to antiviral activity, the plant products have also been demonstrated to exert an immunomodulatory effect by controlling the excessive release of cytokines, which is commonly associated with SARS-CoV-2 infections.
Chapter
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Phenolic compounds, primarily derived from the phenylpropanoid pathway and acetate pathway are plant secondary metabolites that constitute one of the most common and widespread groups of substances in plants playing an important role in plant resistance. Polyphenols are chemical compounds, belonging in the class of antioxidants, which have attracted extensive attention as natural bioactive materials. Polyphenols are found in plant tissues as well as hazardeous residues after food factory processing olive mill wastes (OMW) wich are characterized as phytotoxic and considered a threat to the environment. Thus, there is currently an increasing interest in using of agricultural wastes like Olive Mill Waste Waters-OMWW containing natural polyphenols as non-hazardous organic phytochemical and plant protective substances and substances susch us organic matter, minerals, and nutrients. This review article is focuses on the full utilization of OMWW, which are one of the most polluting food industry wastes, in accordance with the principle zero discharge, strategy and most central waste management option. These substances (mainly from the liquid-phase) result to eco-friendly alternatives of chemical pesticides and other agrochemicals and also contribute to the health protection of the farmers and of the consumers. The recovery of high added-value products from waste plant material such as OMWW is therefore a significant issue in non chemical disease control. Several studies worldwide have investigated and proven their bioactivity potential and their effectiveness against various plant pathogens. The development of sustainable strategies based on the reuse of OMW for plant disease control in view to reduce the use of chemical and synthetic pesticides may have considerable economic benefits.
Preprint
Thanks to the pioneering studies of Østerud and co-workers it is now increasingly understood that natural polyphenols present in marine oils play an essential role in protecting omega-3 lipids from oxidation and autooxidation ensuring that no proinflammatory products are formed after intake as it often happens with assumption of refined omega-3 concentrates. Strong antioxidants exerting multiple biological functions, olive biophenols are ideally suited to functionalize marine oils creating a synergy which has the potential to foster public health across the world. This study identifies suitable avenues to advance the sustainable production of health-beneficial formulations based on newly obtained natural marine oils and olive phenolic extracts. Important educational outcomes for bioeconomy educators conclude the study.
Chapter
Phenolic compounds, primarily derived from the phenylpropanoid pathway and acetate pathway are plant secondary metabolites that constitute one of the most common and widespread groups of substances in plants playing an important role in plant resistance. Polyphenols are chemical compounds, belonging in the class of antioxidants, which have attracted extensive attention as natural bioactive materials. Polyphenols are found in plant tissues as well as hazardeous residues after food factory processing olive mill wastes (OMW) which are characterized as phytotoxic and considered a threat to the environment. Thus, there is currently an increasing interest in using of agricultural wastes like Olive Mill Waste Waters-OMWW containing natural polyphenols as non-hazardous organic phytochemical and plant protective substances and substances such us organic matter, minerals, and nutrients. This review article is focuses on the full utilization of OMWW, which are one of the most polluting food industry wastes, in accordance with the principle zero discharge, strategy and most central waste management option. These substances (mainly from the liquid-phase) result to eco-friendly alternatives of chemical pesticides and other agrochemicals and also contribute to the health protection of the farmers and of the consumers. The recovery of high added-value products from waste plant material such as OMWW is therefore a significant issue in non chemical disease control. Several studies worldwide have investigated and proven their bioactivity potential and their effectiveness against various plant pathogens. The development of sustainable strategies based on the reuse of OMW for plant disease control in view to reduce the use of chemical and synthetic pesticides may have considerable economic benefits.
Article
Antioxidants have been the subject of intense research interest due to their numerous health benefits. In this work, a series of new conjugates of hydroxytyrosol and coumarin were synthesized and evaluated for their free radical scavenging, toxicity and antioxidant mechanism in vitro. The all target compounds 14a–t exhibited better radical scavenging activity than BHT, hydroxytyrosol, and coumarin in both DPPH radical and ABTS⁺ radical cation scavenging assays. The structure-activity relationships study indicated that the number and position of hydroxyl groups on the coumarin ring were vital to a good antioxidant capacity. Furthermore, the most promising compound 14q showed less toxicity in hemolysis assay and weaker antiproliferative effects than BHT against normal WI-38 and GES cells, and enhanced viability of H2O2-induced HepG2 cells. Additionally, 14q decreased the apoptotic percentage of HepG2 cells, reduced the ROS produce and LDH release, and improved GSH and SOD levels in H2O2-treated HepG2 cells. Lastly, 14q exhibited more stability than hydroxytyrosol in methanol solution. These results revealed that conjugations of hydroxytyrosol and coumarin show better antioxidant capacity, and are the efficacious approach to finding novel potential antioxidant.
Article
The SARS-CoV-2 pandemic has caused approximately 6.3 million deaths, mainly due to the acute respiratory distress syndrome or multi-organ failure that characterizes COVID-19 acute disease. Post-acute COVID-19 syndrome, also known as long-COVID, is a condition characterized by a complex of symptoms that affects 10–20% of the individuals who have recovered from the infection. Scientific and clinical evidence demonstrates that long-COVID can develop in both adults and children. It has been hypothesized that multi-organ effects of long-COVID could be associated with the persistence of virus RNA/proteins in host cells, but the real mechanism remains to be elucidated. Therefore, we sought to determine the effects of the exogenous expression of the papain-like protease (PLpro) domain of the non-structural protein (NSP3) of SARS-CoV-2 in polarized human airway (Calu-3), intestinal (Caco-2), and liver (HepG2) epithelial cells, and to evaluate the ability of the natural antioxidant hydroxytyrosol (HXT) in neutralizing these effects. Our results demonstrated that PLpro was able to induce a cascade of inflammatory genes and proteins (mainly associated with the interferon pathway) and increase the apoptotic rate and expression of several oxidative stress markers in all evaluated epithelial cells. Noteably, the treatment with 10 μM HXT reverted PL-pro-dependent effects almost completely. This study provides the first evidence that SARS-CoV-2 PLpro remaining in host cells after viral clearance may contribute to the pathogenetic mechanisms of long-COVID. These effects may be counteracted by natural antioxidants. Further clinical and experimental studies are necessary to confirm this hypothesis.
Article
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Coronavirus disease 2019 (COVID-19) is a recently emerged pandemic caused by a novel virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This disease is communicable and mainly affects the respiratory tract. The outbreak of this disease has greatly influenced human health and economic activities worldwide. The absence of any medication for this infection highlights the urgent need for the development of alternative methods for managing the spread of the disease. Our immune system operates based on a complex array of cells, processes, and chemicals that continuously protect our body from invading pathogens, including viruses, toxins, and bacteria. The present study was conducted to perform a comprehensive review of all dietary treatments for boosting immunity against viral infections. No study was found to explicitly support the use of any healthy foods or supplements to protect against COVID-19. However, this study offers details on well-researched functional foods and supplements that typically improve the immune response, which could be helpful against this newly emerged pandemic. Altern Ther Health Med. 2020 Dec 29; AT6564. Online ahead of print
Coronavirus disease 2019 (COVID-19) is a recently emerged pandemic caused by a novel virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This disease is communicable and mainly affects the respiratory tract. The outbreak of this disease has greatly influenced human health and economic activities worldwide. The absence of any medication for this infection highlights the urgent need for the development of alternative methods for managing the spread of the disease. Our immune system operates based on a complex array of cells, processes, and chemicals that continuously protect our body from invading pathogens, including viruses, toxins, and bacteria. The present study was conducted to perform a comprehensive review of all dietary treatments for boosting immunity against viral infections. No study was found to explicitly support the use of any healthy foods or supplements to protect against COVID-19. However, this study offers details on well-researched functional foods and supplements that typically improve the immune response, which could be helpful against this newly emerged pandemic.
Article
The European dependencies for raw materials supply from foreign countries have been unquestionably shown by COVID‐19 outbreak and have become particular evident from the slow response to the need for high quality personal protective equipment (PPEs). Among all medical devices, surgical face masks have earned themselves a primary role for the containment of the epidemic. In this context, our work aims at improving the barrier effect of surgical mask by depositing on their external surface a mixture of bioactive compounds, mainly polyphenols, extracted from agronomical sources. The main objective is the integration of the biorefining of agri‐food solid wastes with the potential virucidal properties of the polyphenolic extracts for the treatment of PPEs. The experimental workflow proposed in this work. Vegetable wastes are selected, dried, crush into powder and extracted with 70 % ethanol. The solution is used to cover the surface of surgical face masks and improve their barrier effect against pathogens.
Article
This research was aimed to evaluate the in vitro antiviral effect and the mechanism of the effect of Peganum. harmala seeds extract against influenza A virus infection using Madin-Darby canine kidney (MDCK) cells. In this research, ethyl alcohol extract of P. harmala seeds and its total alkaloids was prepared. The potential antiviral activity of the extract and its total alkaloids against influenza A/Puerto Rico/8/34 (H1N1; PR8) virus was assessed. The mode of action of the extract to inhibit influenza replication was investigated using virucidal activity, hemagglutination inhibition assay, time of addition assays, RNA replication, western blot analysis and RNA polymerase blocking assay. The crud extract of P. harmala seed and its total alkaloids showed the best inhibitory effect against influenza A virus replication in MDCK cells using MTT assay, TCID50 method and hemagglutination assay. Our results indicated that the extract inhibits viral RNA replication and viral polymerase activity but did not effect on hemagglutination inhibition and virucidal activity. This study showed that, in vitro antiviral activity of P. harmala seed extract against influenza virus is most probably associated with inhibiting viral RNA transcription. Therefore, this extract and its total alkaloid should be further characterized to be developed as anti-influenza A virus agent.
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Six secoiridoid glucosides, lucidumoside C (1), oleoside dimethylester (2), neonuezhenide (3), oleuropein (4), ligustroside (5) and lucidumoside A (6), isolated from the fruits of Ligustrum lucidum (Oleaceae), were examined in vitro for their activities against four strains of pathogenic viruses, namely herpes simplex type I virus (HSV-1), influenza type A virus (Flu A), respiratory syncytial virus (RSV) and parainfluenza type 3 virus (Para 3). Antiviral activities were evaluated by the cytopathic effect (CPE) inhibitory assay. The purpose was to check if the antioxidative potency of these glucosides correlated with their antiviral potency. Results showed that none of the glucosides had any significant activity against HSV-1 and Flu A. Oleuropein, however, showed significant antiviral activities against RSV and Para 3 with IC50 value of 23.4 and 11.7 microg/ml, respectively. Lucidumoside C, oleoside dimethylester and ligustroside showed potent or moderate antiviral activities against Para 3 with IC50 values of 15.6-20.8 microg/ml. These results also documented that the anti-oxidative potency of these secoiriodoid glucosides was not directly related to their antiviral effects.
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Fruit and vegetable simple and polyphenols are potent antioxidants. One of the most effective in terms of free radical scavenging is 3,4-dihydroxyphenyl ethanol or hydroxytyrosol (HT), a simple phenol found predominantly in Olea europea, or the olive plant. HT is most abundant in the aqueous fraction of olive pulp with trace amounts in the olive oil fraction and in the leaves. For these experiments, we evaluated the anti-inflammatory activity of olive vegetation water (OVW), which we showed previously to have potent antioxidant activity. Because some simple phenols and polyphenols with antioxidant activity have shown varying anti-inflammatory activities, we tested OVW and HT for their ability to inhibit the production of tumor necrosis factor-alpha (TNF-alpha), a pivotal cytokine in inflammation. In lipopolysaccharide (LPS)-treated BALB/c mice, a model system of inflammation, OVW at a dose of 125 mg/mouse (500 mg/kg) reduced serum TNF-alpha levels by 95%. In the human monocyte cell line, THP-1, OVW reduced LPS-induced TNF-alpha production by 50% at a concentration of 0.5 g/L (equivalent to approximately 0.03 g/L simple and polyphenols). OVW had no toxic effects in vitro or in vivo. When OVW was combined with glucosamine, a component of proteoglycans and glycoproteins that was shown to decrease inducible nitric oxide synthase production in cultured macrophage cells, the 2 compounds acted synergistically to reduce serum TNF-alpha levels in LPS-treated mice. These findings suggest that a combination of OVW and glucosamine may be an effective therapy for a variety of inflammatory processes, including rheumatoid and osteoarthritis.
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Newly pressed extra-virgin olive oil contains oleocanthal--a compound whose pungency induces a strong stinging sensation in the throat, not unlike that caused by solutions of the non-steroidal anti-inflammatory drug ibuprofen. We show here that this similar perception seems to be an indicator of a shared pharmacological activity, with oleocanthal acting as a natural anti-inflammatory compound that has a potency and profile strikingly similar to that of ibuprofen. Although structurally dissimilar, both these molecules inhibit the same cyclooxygenase enzymes in the prostaglandin-biosynthesis pathway.
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To prevent the introduction of highly pathogenic avian influenza (HPAI) into Japan, we examined chicken imported from China for viruses. For virus isolation, we used embryonated chicken eggs and a total of 473 samples of frozen meat and bone marrow collected between June 2001 and July 2002. The Newcastle disease virus (NDV) was isolated from 11 (2.3%) specimens and the avian influenza virus (AIV) from 13 (2.7%) specimens. No HPAI virus was included. On the basis of pathogenicity-index tests, all of the NDV isolates were identified as velogenic strains with112RRQKR-F117sequences at the F-protein cleavage site, as is typical of virulent NDV strains. As a result of phylogenetic analysis basedon the F gene, all NDV isolates were classified as belonging to genotype VII, which is prevalent mainly in East Asia and is especially closely related to strains prevalent in China. All AIV isolates were identified as H9N2 subtypes. Intravenous inoculation tests using 3AIV isolates showed no disease symptoms in chicken. Phylogenetic analysis based on the HA gene showed all AIV isolates to belong in the cluster of isolates found mainly in chicken from China.
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The Mediterranean diet, rich in fresh fruits and vegetables, has been associated with a lower incidence of cardiovascular disease and cancer, partly because of its high proportion of bioactive compounds such as vitamins, flavonoids and polyphenols. The major lipid component of such diet is the drupe-derived olive oil, that can be distinguished from other seed oils for the peculiar composition of its non-triglyceride fraction. In fact, several minor components, including polyphenols, grant the oil its particular taste and aroma. Oleuropein, the most abundant among these components, has been shown to be a potent antioxidant endowed with antiinflammatory properties. We investigated the effects of oleuropein on NO release in cell culture and its activity toward nitric oxide synthase (iNOS) expression. The results show that oleuropein dose-dependently enhance nitrite production in LPS-challenged mouse macrophages. This effect was blocked by the iNOS inhibitor L-NAME, indicating increased iNOS activity. Also, Western blot analysis of cell homogenates show that oleuropein increases iNOS expression in such cells. Taken together, our data suggest that, during endotoxin challenge, oleuropein potentiates the macrophage-mediated response, resulting in higher NO production, currently believed to be beneficial for cellular and organismal protection.
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Plants in the Mediterranean basin, such as vine and olive trees, have developed an array of antioxidant defences to protect themselves from environmental stress. Accordingly, the incidence of coronary heart disease and certain cancers is lower in the Mediterranean area, where olive oil is the dietary fat of choice. As opposed to other vegetable oils, extra virgin olive oil, which is obtained by physical pressure from a whole fruit, is rich in phenolic components that are responsible for the particular stability of the oil. We have investigated the scavenging actions of some olive oil phenolics, namely hydroxytyrosol and oleuropein, with respect to superoxide anion generation, neutrophils respiratory burst, and hypochlorous acid. The low EC50s indicate that both compounds are potent scavengers of superoxide radicals and inhibitors of neutrophils respiratory burst: whenever demonstratedin vivo,these properties may partially explain the observed lower incidence of CHD and cancer associated with the Mediterranean diet.
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High postprandial levels of TAG may further induce endothelial dysfunction and inflammation in subjects with high fasting levels of TAG, an effect that seems to be related to oxidative stress. The present study investigated whether minor compounds of olive oil with antioxidant activity decrease postprandial levels of soluble isoforms of intercellular adhesion molecule 1 (sICAM-1) and vascular cell adhesion molecule 1 (sVCAM-1), as surrogate markers of vascular inflammation, after a high-fat meal. A randomized crossover and blind trial on fourteen healthy and fourteen hypertriacylglycerolaemic subjects was performed. The study involved a 1-week adaptation lead-in period on a National Cholesterol Education Program Step I diet supplemented with extra-virgin olive oil (EVOO) containing 1125 mg polyphenols/kg and 350 mg tocopherols/kg, or refined olive oil (ROO) with no polyphenols or tocopherols. After a 12 h fast, the participants ate a high-fat meal enriched in EVOO or ROO (50 g/m2 body surface area), which on average provided 3700 kJ energy with a macronutrient profile of 72% fat, 22% carbohydrate and 6% protein. Blood samples drawn hourly over the following 8 h demonstrated a similar postprandial TAG response for both EVOO and ROO meals. However, in both healthy and hypertriacylglycerolaemic subjects the net incremental area under the curve for sICAM-1 and sVCAM-1 were significantly lower after the EVOO meal. In conclusion,the consumption of EVOO with a high content of minor antioxidant compounds may have postprandial anti-inflammatory protective effects.
Article
Oxidation of low density lipoproteins maybe a factor in the development of atherosclerosis. The Mediterranean diet rich in vegetables, grains, legumes, fruits, and oils, mainly olive oil, has been suggested to reduce the incidence of coronary heart disease, because of its low saturated and high monounsaturated fatty acids content. It is also possible that the natural antioxidants in the oil help to prevent lipid oxidation, e.g. that of low density lipoproteins, thus retarding the formation of atherosclerotic plaques. First-pressed, extra-virgin olive oil contains appreciable amounts of polyphenolic compounds that prevent its autoxidation and are responsible for its high stability. We tested these compounds on low density lipoprotein oxidation and found an inhibitory effect, at low concentrations, on various indexes of lipid oxidation (vitamin E content, formation of thiobarbituric acid-reacting substances, lipid peroxides, levels of polyunsaturated fatty acids, protein modification, conjugated diene formation). Our data suggest that natural antioxidants could play a role in inhibiting the formation of cytotoxic products such as lipid peroxides thus retarding the onset of the atherosclerotic damage.
Article
The antimicrobial potential of eight phenolic compounds isolated from olive cake was tested against the growth of Escherichia coli, Klebsiella pneumoniae, Bacillus cereus, Aspergillus flavus and Aspergillus parasiticus. The phenolic compounds included p-hydroxy benzoic, vanillic, caffeic, protocatechuic, syringic, and p-coumaric acids, oleuropein and quercetin. Caffeic and protocatechuic acids (0.3 mg/ml) inhibited the growth of E. coli and K. pneumoniae. The same compounds apart from syringic acid (0.5 mg/ml) completely inhibited the growth of B. cereus. Oleuropein, and p-hydroxy benzoic, vanillic and p-coumaric acids (0.4 mg/ml) completely inhibited the growth of E. coli, K. pneumoniae and B. cereus. Vanillic and caffeic acids (0.2 mg/ml) completely inhibited the growth and aflatoxin production by both A. flavus and A. parasiticus, whereas the complete inhibition of the moulds was attained with 0.3 mg/ml p-hydroxy benzoic, protocatechuic, syringic, and p-coumaric acids and quercetin.
Article
Secoiridoides (oleuropein and derivatives), one of the major classes of polyphenol contained in olives and olive oil, have recently been shown to inhibit or delay the rate of growth of a range of bacteria and microfungi but there are no data in the literature concerning the possible employment of these secoiridoides as antimicrobial agents against pathogenic bacteria in man. In this study five ATCC standard bacterial strains (Haemophilus influenzae ATCC 9006, Moraxella catarrhalis ATCC 8176, Salmonella typhi ATCC 6539, Vibrio parahaemolyticus ATCC 17802 and Staphylococcus aureus ATCC 25923) and 44 fresh clinical isolates (Haemophilus influenzae, eight strains, Moraxella catarrhalis, six strains, Salmonella species, 15 strains, Vibrio cholerae, one strain, Vibrio alginolyticus, two strains, Vibrio parahaemolyticus, one strain, Staphylococcus aureus, five penicillin-susceptible strains and six penicillin-resistant strains), causal agents of intestinal or respiratory tract infections in man, were tested for in-vitro susceptibility to two olive (Olea europaea) secoiridoides, oleuropein (the bitter principle of olives) and hydroxytyrosol (derived from oleuropein by enzymatic hydrolysis and responsible for the high stability of olive oil). The minimum inhibitory concentrations (MICs) calculated in our study are evidence of the broad antimicrobial activity of hydroxytyrosol against these bacterial strains (MIC values between 0.24 and 7.85 μg mL−1 for ATCC strains and between 0.97 and 31.25 μg mL−1 for clinically isolated strains). Furthermore oleuropein also inhibited (although to a much lesser extent) the growth of several bacterial strains (MIC values between 62.5 and 500 μg mL−1 for ATCC strains and between 31.25 and 250 μg mL−1 for clinical isolates); oleuropein was ineffective against Haemophilus influenzae and Moraxella catarrhalis. These data indicate that in addition to the potential employment of its active principles as food additives or in integrated pest-management programs, Olea europaea can be considered a potential source of promising antimicrobial agents for treatment of intestinal or respiratory tract infections in man.
Article
Hydroxytyrosol, a polyphenol with very interesting antioxidant properties, which naturally occurs in virgin olive oil and mainly in olive oil mill waste waters, was synthesized by reducing 3, 4-dihydroxyphenylacetic acid with LiAlH(4) in tetrahydrofuran under refluxing for 2 h. The yield of reaction was 82.8%. The spectroscopic and HPLC data of the synthesized compound proved to coincide fully with those of a pure sample obtained by the chromatographic recovery from olive oil mill waste waters (yield = 91 mg/L). This synthetic method appears to be the most convenient compared with those reported in the literature and is more convenient than the chromatographic recovery. The tri- and diacetyl derivatives of the synthetic compound were also prepared for structure-bioactivity relationship studies. A brief discussion is given on the economical and ecological aspects regarding the production of hydroxytyrosol.
Article
On the basis of the results obtained with pilot studies conducted in vitro on human low density lipoprotein (LDL) and on cell cultures (Caco-2), which had indicated the ability of certain molecules present in olive oil to inhibit prooxidative processes, an in vivo study was made of laboratory rabbits fed special diets. Three different diets were prepared: a standard diet for rabbits (diet A), a standard diet for rabbits modified by the addition of 10% (w/w) extra virgin olive oil (diet B), a modified standard diet for rabbits (diet C) differing from diet B only in the addition of 7 mg kg(-1) of oleuropein. A series of biochemical parameters was therefore identified, both in the rabbit plasma and the related isolated LDL, before and after Cu-induced oxidation. The following, in particular, were selected: (i) biophenols, vitamins E and C, uric acid, and total, free, and ester cholesterol in the plasma; (ii) proteins, triglycerides, phospholipids, and total, free, and ester cholesterol in the native LDL (for the latter, the dimensions were also measured); (iii) lipid hydroperoxides, aldehydes, conjugated dienes, and relative electrophoretic mobility (REM) in the oxidized LDL (ox-LDL). In an attempt to summarize the results obtained, it can be said that this investigation has not only verified the antioxidant efficacy of extra virgin olive oil biophenols and, in particular, of oleuropein, but has also revealed a series of thus far unknown effects of the latter on the plasmatic lipid situation. In fact, the addition of oleuropein in diet C increased the ability of LDL to resist oxidation (less conjugated diene formation) and, at the same time, reduced the plasmatic levels of total, free, and ester cholesterol (-15, -12, and -17%, respectively), giving rise to a redistribution of the lipidic components of LDL (greater phospholipid and cholesterol amounts) with an indirect effect on their dimensions (bigger by about 12%).
Article
(3,4-Dihydroxyphenyl)ethanol, commonly known as hydroxytyrosol (1), is the major phenolic antioxidant compound in olive oil, and it contributes to the beneficial properties of olive oil. Bioavailability and metabolism studies of this compound are extremely limited, in part, related to unavailability of radiolabeled compound. Studies with radiolabeled compounds enable use of sensitive radiometric analytical methods as well as aiding elucidation of metabolic and elimination pathways. In the present study a route for the formation of hydroxytyrosol (1), by reduction of the corresponding acid 2 with tetrabutylammonium boronate, was found. Methods for the incorporation of a tritium label in 1 were investigated and successfully accomplished. Tritiated hydroxytyrosol (1t) was synthesized with a specific activity of 66 Ci/mol. The stability of unlabeled and labeled hydroxytyrosol was also investigated.
Article
Hydroxytyrosol is the most potent phenolic antioxidant of olive oil and olive mill waste water (OMWW) and its biological activities have stimulated research on its potential role in cardiovascular protection. However, evidence of the absorption of OMWW phenolics and on their possible in vivo activity has, until now, never been provided. Three groups male Sprague-Dawley rats were administered 1, 5, or 10 mg/Kg of the OMWW extract, respectively, providing 41.4, 207, and 414 microg/Kg of hydroxytyrosol, respectively. Urine was collected for 24 h and the urinary levels of hydroxytyrosol were quantified by mass spectrometry. Hydroxytyrosol was dose-dependently (R(2) = 0.95) absorbed and excreted in the urines mostly as a glucuronide conjugate. Further, the administration of an hydroxytyrosol-rich OMWW extract (10 mg/kg) to the rats was also associated with an increase of their plasma antioxidant capacity. Future experiments will eventually further clarify its metabolic fate and its in vivo actions.
Article
Hydroxytyrosol (HTyr), a natural ortho-diphenolic antioxidant with health-beneficial properties that mainly occurs in virgin olive oil and olive oil mill waste waters (also known as vegetative waters), has been enzymatically synthesized using mushroom tyrosinase. This o-diphenol (not commercially available) was obtained from its monophenolic precursor tyrosol (commercially available) in the presence of both tyrosinase and ascorbic acid. The reaction synthesis is continuous, easy to perform, and adaptable to a bioreactor for industrial purposes. The HTyr concentration is time-predicted, and the yield of reaction can be 100%. The synthesis method reported here is an alternative approach to obtain this compound in an environmentally friendly way.
Article
Recent in vitro studies have demonstrated antioxidant properties of some virgin olive oil phenolic compounds. One of the prerequisites to extrapolate these data to an in vivo situation is the knowledge of their bioavailability in humans. In the present work we describe an analytical method which enables us to perform hydroxytyrosol and tyrosol quantitative determinations in human urine. This method was successfully used in bioavailability studies of both phenolic compounds after acute olive oil administration. Virgin olive oil was administered to healthy volunteers after a low phenolic diet. The dose administered of both phenolic compounds was estimated in reference to free forms of hydroxytyrosol and tyrosol present in virgin olive oil extracts before and after being submitted to hydrolytic conditions. These conditions mimic those occurring during digestion. Urine samples were collected before and after acute olive oil intake and analyzed by capillary gas chromatography-mass spectrometry. Hydroxytyrosol and tyrosol urinary recovery increased in response to olive oil administration, obtaining maximal values in the first 4 h. Our results further indicate that hydroxytyrosol and tyrosol are mainly excreted in conjugated form, since only 5.9 +/- 1.4% (hydroxytyrosol) and 13.8 +/- 5.4% (tyrosol) of the total amounts excreted in urine were in free form.
Article
We have recently demonstrated, in humans, the bioavailability of hydroxytyrosol (3,4-dihydroxyphenylethanol; HT), one of the major antioxidant components of virgin olive oil. In particular, we reported that this compound is present in lipoproteins involved in atherosclerotic processes and is excreted in the urine mainly as glucuronide-conjugate. The aim of the present study was to elucidate, in humans, the metabolic fate of HT after ingestion of virgin olive oil. After administration of virgin olive oil, 24-hour urine collections of healthy volunteers were prepared for gas chromatography-mass spectrometry analyses in order to identify and quantify HT and its metabolites homovanillic alcohol (HVA1c) and homovanillic acid (HVA). The results indicate that this compound undergoes the action of catechol-O-methyl transferase (COMT), enzymes involved in the catecholamine catabolism, resulting in an enhanced excretion of HVA1c. We also found a significant increase of HVA, indicating an oxidation of the ethanolic residue of HT and/or of HVA1c in humans. The excretion of both metabolites significantly correlated with the dose of administered HT.
Article
The activity of oleuropein, a phenolic glycoside contained in olive oil, was investigated in vitro against Mycoplasma hominis, Mycoplasma fermentans, Mycoplasma pneumoniae and Mycoplasma pirum. Oleuropein inhibited mycoplasmas at concentrations from 20 to 320 mg/l. The MICs of oleuropein to M. pneumoniae, M. pirum, M. hominis and M. fermentans were 160, 320, 20 and 20 mg/l, respectively.
Article
A commercial plant extract derived from olive tree leaf (Olea europaea) (LExt) and its major compound, oleuropein (Ole), inhibited the in vitro infectivity of the viral haemorrhagic septicaemia virus (VHSV), a salmonid rhabdovirus. Incubation of virus with LExt or Ole before infection reduced the viral infectivity to 10 and 30%, respectively. Furthermore, LExt drastically decreased VHSV titers and viral protein accumulation (virucidal effect) in a dose dependent manner when added to cell monolayers 36 h post-infection. On the other hand, both the LExt and Ole were able to inhibit cell-to-cell membrane fusion induced by VHSV in uninfected cells, suggesting interactions with viral envelope. Therefore, we propose that O. europaea could be used as a potential source of promising natural antivirals, which have demonstrated to lack impact on health and environment. In addition, Ole could be used to design other related antiviral agents.
Article
Oleuropein (Chemical Abstracts Service registry number 32619-42-4), a bitter-tasting secoiridoid glucoside commonly found in leaves of the olive tree as well as in olives (Olea europaea L.), was found to be hydrolyzed by the beta-glucosidase (EC 3.2.1.2.1) produced by oleuropeinolytic Lactobacillus plantarum-type strains. Three strains, designated B17, B20, and B21, were isolated from the brine of naturally ripe olives not treated with alkali. These strains were rod-shaped forms, grown at a pH 3.5 limit, and tolerated 1% oleuropein and 8% NaCl in the growth medium. The beta-glucosidase produced hydrolyzed 5-bromo-4-chloro-3-indolyl-beta-d-glucopy-ranoside as well as oleuropein. The presence of 2% glucose in the medium inhibited activity by 40 to 50%, depending on the bacterial strain. Chromatographic analysis of the trimethylsilyl derivatives of the products obtained after 7 days of incubation at 30 degrees C of strain B21 showed all the hydrolysis products of oleuropein, i.e., aglycone, iridoid monoterpen, and 3,4-dihydroxyphenylethanol (hydroxytyrosol). Oleuropein and its aglycone after 21 days of incubation decreased to trace levels with the simultaneous increase in concentration of beta-3,4-dihydroxyphenylethanol.
Article
We report molecular modeling and functional confirmation of Ole and HT binding to HIV-1 integrase. Docking simulations identified two binding regions for Ole within the integrase active site. Region I encompasses the conserved D64-D116-E152 motif, while region II involves the flexible loop region formed by amino acid residues 140-149. HT, on the other hand, binds to region II. Both Ole and HT exhibit favorable interactions with important amino acid residues through strong H-bonding and van der Waals contacts, predicting integrase inhibition. To test and confirm modeling predictions, we examined the effect of Ole and HT on HIV-1 integrase activities including 3'-processing, strand transfer, and disintegration. Ole and HT exhibit dose-dependent inhibition on all three activities, with EC(50)s in the nanomolar range. These studies demonstrate that molecular modeling of target-ligand interaction coupled with structural-activity analysis should facilitate the design and identification of innovative integrase inhibitors and other therapeutics.
Article
We have identified oleuropein (Ole) and hydroxytyrosol (HT) as a unique class of HIV-1 inhibitors from olive leaf extracts effective against viral fusion and integration. We used molecular docking simulation to study the interactions of Ole and HT with viral targets. We find that Ole and HT bind to the conserved hydrophobic pocket on the surface of the HIV-gp41 fusion domain by hydrogen bonds with Q577 and hydrophobic interactions with I573, G572, and L568 on the gp41 N-terminal heptad repeat peptide N36, interfering with formation of the gp41 fusion-active core. To test and confirm modeling predications, we examined the effect of Ole and HT on HIV-1 fusion complex formation using native polyacrylamide gel electrophoresis and circular dichroism spectroscopy. Ole and HT exhibit dose-dependent inhibition on HIV-1 fusion core formation with EC(50)s of 66-58nM, with no detectable toxicity. Our findings on effects of HIV-1 integrase are reported in the subsequent article.
Article
We investigated the antiviral activity of olive leaf extract (OLE) preparations standardized by liquid chromatography-coupled mass spectrometry (LC-MS) against HIV-1 infection and replication. We find that OLE inhibits acute infection and cell-to-cell transmission of HIV-1 as assayed by syncytia formation using uninfected MT2 cells co-cultured with HIV-1-infected H9 T lymphocytes. OLE also inhibits HIV-1 replication as assayed by p24 expression in infected H9 cells. These anti-HIV effects of OLE are dose dependent, with EC(50)s of around 0.2 microg/ml. In the effective dose range, no cytotoxicity on uninfected target cells was detected. The therapeutic index of OLE is above 5000. To identify viral and host targets for OLE, we characterized gene expression profiles associated with HIV-1 infection and OLE treatment using cDNA microarrays. HIV-1 infection modulates the expression patterns of cellular genes involved in apoptosis, stress, cytokine, protein kinase C, and hedgehog signaling. HIV-1 infection up-regulates the expression of the heat-shock proteins hsp27 and hsp90, the DNA damage inducible transcript 1 gadd45, the p53-binding protein mdm2, and the hedgehog signal protein patched 1, while it down-regulates the expression of the anti-apoptotic BCL2-associated X protein Bax. Treatment with OLE reverses many of these HIV-1 infection-associated changes. Treatment of HIV-1-infected cells with OLE also up-regulates the expression of the apoptosis inhibitor proteins IAP1 and 2, as well as the calcium and protein kinase C pathway signaling molecules IL-2, IL-2Ralpha, and ornithine decarboxylase ODC1.
Article
Olive oil is the primary source of fat in the Mediterranean diet which is associated with a low mortality for cardiovascular disease. In spite of this, data concerning olive oil consumption and primary end points for cardiovascular disease are scarce. However, a large body of knowledge exists providing evidence of the benefits of olive oil consumption on secondary end points for cardiovascular disease. The benefits of olive oil consumption are beyond a mere reduction of the low density lipoprotein cholesterol. Here, we review the state of the art concerning the knowledge of the most important biological and clinical effects related to the intake of olive oil rich diets on lipoprotein metabolism, oxidative damage, inflammation, endothelial dysfunction, blood pressure, thrombosis, and carbohydrate metabolism. The extent to which we possess evidence of the health benefits of olive oil minor components is also assessed. The wide range of anti-atherogenic effects associated with olive oil consumption could contribute to explain the low rate of cardiovascular mortality found in Southern European Mediterranean countries, in comparison with other western countries, despite a high prevalence of coronary heart disease risk factors.
Article
Recent experimental study found that OLE (olive leaf extract) has anti-HIV activity by blocking the HIV virus entry to host cells [Lee-Huang, S., Zhang, L., Huang, P.L., Chang, Y. and Huang, P.L. (2003) Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment. Biochem. Biophys. Res. Commun. 307, 1029; Lee-Huang, S., Huang, P.L., Zhang, D., Lee, J.W., Bao, J., Sun, Y., Chang, Y.-Tae, Zhang, J.Z.H. and Huang, P.L. (2007) Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol. Biochem. Biophys. Res. Commun. 354, 872-878, 879-884]. As part of a joint experimental and theoretical effort, we report here computational study to help identify and characterize the binding complexes of several main compounds of OLE (olive leaf extract) to HIV-1 envelop protein gp41. A number of possible binding modes are found by docking oleuropein and its metabolites, aglycone, elenolic acid and hydroxytyrosol, onto the hydrophobic pocket on gp41. Detailed OLE-gp41 binding interactions and free energies of binding are obtained through molecular dynamics simulation and MM-PBSA calculation. Specific molecular interactions in our predicted OLE/gp41 complexes are identified and hydroxytyrosol is identified to be the main moiety for binding to gp41. This computational study complements the corresponding experimental investigation and helps establish a good starting point for further refinement of OLE-based gp41 inhibitors.
Article
Infections with influenza A viruses still pose a major threat to humans and several animal species. The occurrence of highly pathogenic avian influenza viruses of the H5N1 subtype capable to infect and kill humans highlights the urgent need for new and efficient countermeasures against this viral disease. Here we demonstrate that a polyphenol rich extract (CYSTUS052) from the Mediterranean plant Cistus incanus exerts a potent anti-influenza virus activity in A549 or MDCK cell cultures infected with prototype avian and human influenza strains of different subtypes. CYSTUS052 treatment resulted in a reduction of progeny virus titers of up to two logs. At the effective dose of 50 microg/ml the extract did not exhibit apparent harming effects on cell viability, metabolism or proliferation, which is consistent with the fact that these plant extracts are already used in traditional medicine in southern Europe for centuries without any reported complications. Viruses did not develop resistance to CYSTUS052 when compared to amantadine that resulted in the generation of resistant variants after only a few passages. On a molecular basis the protective effect of CYSTUS052 appears to be mainly due to binding of the polymeric polyphenol components of the extract to the virus surface, thereby inhibiting binding of the hemagglutinin to cellular receptors. Thus, a local application of CYSTUS052 at the viral entry routes may be a promising approach that may help to protect from influenza virus infections.
Com-putational study of bindings of olive leaf extract (OLE) to HIV-1 fusion protein gp41 Phytochemistry: ibuprofen-like activity in extra-virgin olive oil
  • J Bao
  • D W Zhang
  • J Z Zhang
  • P L Huang
  • P L Huang
  • Lee
  • S K Huang
  • Yamada
Bao, J., Zhang, D.W., Zhang, J.Z., Huang, P.L., Huang, P.L., Lee-Huang, S., 2007. Com-putational study of bindings of olive leaf extract (OLE) to HIV-1 fusion protein gp41. FEBS Lett. 581, 2737–2742. r44 K. Yamada et al. / Antiviral Research 83 (2009) 35–44 Beauchamp, G.K., Keast, R.S., Morel, D., Lin, J., Pika, J., Han, Q., Lee, C.H., Smith, A.B., Breslin, P.A., 2005. Phytochemistry: ibuprofen-like activity in extra-virgin olive oil. Nature 437, 45–46
  • K Yamada
K. Yamada et al. / Antiviral Research 83 (2009) 35–44
  • P M Furneri
  • A Marino
  • A Saija
  • N Uccella
  • G Bisignano
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Low density lipoprotein oxidation is inhibited in vitro by olive oil constituents
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