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Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment
Abstract
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.
... In order to utilize oleuropein and other bioactive components within OL effectively enough, they should be extracted from olive leaf. Olive leaf extract (OLE) contains compounds with potent antimicrobial activities against bacteria, fungi, and mycoplasma (Huang et al., 2003). Also, Aliabadi et al. (2012) indicated that using aqueous OLE had beneficial effects in controlling the microbial infections because it is a potent source of polyphenols having antioxidant, antimicrobial, anti-inflammatory and antiviral properties. ...
... Based on the present results in tem of improving semen quality of bucks treated with OLE, several authors indicated that olive leaf or its extract is one of the potent source of plant polyphenols having antioxidant, antimicrobial (against bacteria, fungi, and mycoplasma), antiviral and anti-inflammatory, properties (Suresh et al., 2009;Aliabadi et al., 2012). The most phenolic components of this content is oleuropein, which gives the better taste to olive and its oil (Huang et al., 2003;Periera et al., 2007). Flavonoids and phenolic compounds obtained from olive leaf are known to have diverse biological activities and may also be responsible for the pharmacological actions of olive leaf or, at least synergistically reinforcing those actions (Abaza et al., 2011). ...
the present study was designed to investigate the efficacy of different dietary levels of ethanolic olive leaf extract (OLE), as a source of natural antioxidants, on quality and production of semen, some enzymes activities and testosterone concentration in blood serum and some seminal plasma characteristics of APRI rabbit bucks. A total of 24 mature rabbit bucks of APRI line (3-3.4 kg live body weight and 9-12 months of age) were divided into four similar groups, 6 bucks in each. Bucks in the 1 st group were fed a reference diet (17.75% CP and 2500 DE Kcal/Kg diet) without any supplements (G1, control). While, those in the 2 nd (G2), 3 rd (G3) and 4 th (G4) treatment groups were fed the same diet supplemented with olive leaf extract at levels of 0.5, 1 and 1.5 ml/kg diet, respectively. Bucks were fed ad libitum on the experimental diets for a period of 17 wk (8 wk as a treatment period and 9 wk as main semen collection period. Semen was evaluated physically, chemically and by transmission electron microscope (TEM). Results showed that all levels of dietary OLE supplementation increased (P<0.05) total semen volume in G2, G3 and G4 as compared to G1, being the highest in G4. Sperm characteristics, including percentages of progressive motility, livability, abnormality and cell concentration of spermatozoa improved (P<0.05) in G3 and G4 as compared to G2 and G1. Examination of sperm cells in all groups by TEM cleared enhancing the abnormalities in cell membrane and acrosome, axonemeas well as chromatin of spermatozoa in G4 as compared to other groups. Bucks in G4 showed the lowest (P<0.05) peroxidase and fructose testes in seminal plasma as compared to other groups. Activity of LDH in seminal plasma was higher (P<0.05) in all treatment groups than in control one, being the highest in G4 and the lowest in G1. Activity of AST and ALT and testosterone concentration in blood serum were not affected by OLE treatment. Activity of ALP in G4 and LDH activity in G3 and G4 increased (P<0.05) as compared to other groups. Kindling rate and reproductive index were improved (P<0.05) in rabbit does mated by bucks of G3 and G4 as compared to that of G2 and G1, being the highest in G4 (81.67%; 6.5). In conclusion, supplementation of the diet with olive leaf extract, in particular at a level of 1.5 ml/kg, as a natural antioxidants source, is essential for improving reproductive performance and consequently semen quality and fertility of breeding rabbit bucks (natural or artificial mating) without adversely effects on healthy status.
... A result of the hydrolysis of oleuropein are formed elenolic acid and hydroxytyrosol [2-(3,4-dihydroxyphenyl) ethanol] as being other active metabolites (Granados-Principal et al. 2010) (Figure 1). Verbascoside, luteolin-7-glucoside, apigenin 7-glucoside and tyrosol are other important active phenolic compounds included in olive leaves (Lee-Huang et al. 2003). Although phenolic compounds such as tyrosol and especially hydroxytyrosol are minor substances included in olive leaves and oil; they have significant metabolic effects (Di Benedetto et al. 2007;Jemai et al. 2009). ...
... mg/kg (2.647 g 100 g -1 ) and; 966.1±18.1 mg/kg (0.0966 g 100 g -1 ), respectively on the basis of lyophilized dry matter rediluted by water. Lee-Huang et al. (2003) determined the amount of oleuropein and verbascoside as 12.8% (w/w) and 0.38% (w/w) respectively, after extracted for 12 hours at 80 °C and concentrated by lyophilization. That the amount of oleuropein obtained in the present study (1.899±0.011 ...
... so the ever increasing resistant of pathogens towards antibiotics has caused serious health problems 2 that caused increasing interest in antimicrobial effects of plants extracts 3 . Olive tree is one of the medicinal plants that it uses in alternative medicine for thousands of years, Olive plant belongs to Olea europeae L. is typical Mediterranean species where more than 95% of the world total production is localized 5 . And it has been an important source of medicine and nutrition 5 . ...
... Olive tree is one of the medicinal plants that it uses in alternative medicine for thousands of years, Olive plant belongs to Olea europeae L. is typical Mediterranean species where more than 95% of the world total production is localized 5 . And it has been an important source of medicine and nutrition 5 . The leaves of olive plant contain some active compounds include saponine, steroid, and flavonoids to express the desired properties 6 . ...
http://www.indianjournals.com/ijor.aspx?target=ijor:ijphrd&volume=10&issue=6&article=232
... Ten compounds were identified in this work ( Table 2). The quantitative results of the 10 compounds identified showed that the most abundant compound was oleuropein (43.25%), as found by various authors [17,[26][27][28][29][30][31][32]. In addition to oleuropein, other phenolic compounds were identified: verbascoside (13.12%), apigenin-7-glucoside (9.82%), luteolin-7-glucoside (1.34%), hydroxytyrosol (7.32%), rutin (0.76%), vanillic acid (0.65%), luteolin (0.89%), tyrosol (3.15%), and caffeic acid (0.79%). ...
... The quantitative analysis of our sylv.OLE showed notable differences compared to that obtained from non-sylvester olive leaf extract (OLE) in different regions of the world. Lee-Huang et al. [28] analyzed the OLE and found that this extract contains; oleuropein (12.8%), verbascoside (0.38%), luteolin-7-glucoside (0.68%), rutin (0.34%), apigenin-7-glucoside (0.18%), and luteolin (0.41%). Botsoglou et al. [29] and Hayes et al. [12] quantified various polyphenols in OLE and also reported that oleuropein was the largest fraction present (43.58%), while other polyphenols like hydroxytyrosol (4.56%), luteolin-7-glucoside (21.54%), verbascoside (25.12%), tyrosol (6.58%), and apigenin-7-O-glucoside (30.22%) were also isolated from the leaves. ...
Oleaster (wild olive tree) by-products represent a renewable and low-cost source of biopolyphenols. Leaf extracts (sylv.OLE) of Algerian oleaster, locally called a'hachad (Olea europaea subsp. europaea var. sylvestris), were applied at 1 and 5% (v/w) to raw Halal minced beef (HMB) in order to test its safety and shelf-life prolongation during retail/display. The total phenolic compound content in the extract was 198.7 ± 3.6 mg gallic acid equivalent. Ten compounds were identified in the sylv.OLE by High Performance Liquid Chromatography/Diode Array Detector (HPLC/DAD), of which oleuropein was the most abundant (43.25%). Samples treated with 5% sylv.OLE had significantly higher antimicrobial and antioxidant effects than those treated with 1% extract (p < 0.05). The addition of sylv.OLE reduced psychrotrophic counts as well as the level of pathogens (Salmonella enterica ser. Enteritidis and Shiga toxin-producing Escherichia coli O157:H7). A thiobarbituric acid reactive substance (TBARS) value of 2.42 ± 0.11 was reached throughout six days of retail/display in control samples, while the addition of 5% sylv.OLE reduced TBARS value by 58% (p < 0.05). The presence of sylv.OLE at the tested concentrations did not negatively influence the overall acceptability and bitterness of HMB.
... The antiviral activity has only been described on olive leaves and was found against viral haemorrhagic septicaemia rhabdovirus (VHSV) [17], HIV-1 [18] and Newcastle disease virus (NDV) [19]. However, no work described the antiviral activity of olive stems or twigs. ...
... Oleuropein also showed antiviral activities, such as anti HIV activity by regulation of gene expression mediated by HIV infection [18], binding to fusion protein gp41 [38], anti HSV-2 activity by interacting with the viral envelope [39], anti newcastle disease virus (NDV) activity by its effect on viral gene expression [19], and anti haemorrhagic septicaemia rhabdovirus (VHSV) activity by its virucidal effect [17]. ...
... HIV etki gösterdiği bildirilmiş, oleuropein ve metaboliti olan hidroksitirozolün ayrı ayrı veya birlikte kullanımı ile virüsün hücreye girişi ve hücreye entegrasyonunun önlendiği belirtilmiştir. 65 Micol Avusturalyada 18-54 yaş arası sigara içmeyen, herhangi bir kardiyovasküler hastalığı veya diyabeti bulunmayan sağlıklı ve gönüllü 11 erkek randomize tek kör çalışmaya dahil edilmiştir. Katılımcılara 7 günlük periyotlarla besin tüketim sıklığı anketi uygulanmış, non-steroid antiinflamatuar ilaç ve asprin benzeri kan sulandırıcı ilaç alımı sorgulanmış,besin alımlarının polifenol içerikleri düzenli olarak takip edilmiş, yüksek polifenol içeren diyet tüketenler ve antioksidan besin destekleri alanlar çalışmadan çıkartılmıştır. ...
Z ZE ET T Zeytin ağacının sadece meyvesi ve meyvesinden elde edilen yağı değil, aynı zamanda yap-rağı da insan sağlığı açısından oldukça önemlidir. Yüzyıllardan beri zeytin ağacının yetiştiği coğ-rafyalarda zeytin yaprağı, geleneksek tedavide ilaç olarak kullanılmıştır ve kullanılmaktadır. Günümüzde de zeytin yaprağının sağlık açısından faydalarını gösteren birçok bilimsel çalışma mev-cuttur. Zeytin yaprağının bileşiminde birçok fenolik bileşen bulunmaktadır. Zeytin yaprağının eks-traktlarında tanımlanan en bilinen fenolik bileşikler ; oleuropein, hidroksitirozol, verbaskozid, apigenin 7-glukozid ve luteloin 7-glukozid'tir. Bu fenolik bileşenler dünya çapında bilim insanla-rının ilgisini uyandırmakta, hayvan ve insan deneyleri üzerinde sağlık açısından yararları rapor edilmektedir. Bu sağlık yararı çalışmaları genellikle antioksidan etki, anti-hipertansif etki, hipogli-semik etki, hipokolesterolemik etki, kardiyoprotektif etki, anti-inflamatuar etki ve antimikrobiyal etki üzerine yoğunlaşmıştır. Zeytin yaprağının sağlık üzerine olumlu etkileri umut verici olmasına rağmen, bu biyolojik aktif bileşenler ile diğer besin maddeleri arasında muhtemel etkileşimlerin daha iyi anlaşılması, insanlar üzerinde yararlı etkiler sağladığının gösterilmesi ve tıbbi tedavide kul-lanabilmek için optimum dozun belirlenmesi gibi sıkıntılar mevcuttur. Zeytin yaprağı ekstresinin veya zeytin yaprağı bileşenlerinin farklı dozajlarda güvenli olup olmadığını incelemek için daha geniş ve daha kapsamlı çalışmalara ihtiyaç vardır. Zeytin yaprağı ve fenolik bileşenlerinin terapö-tik etkinliği konusunda, altta yatan mekanizmaları anlamamıza yardım sağlayacak daha detaylı araştırmalar yapılması bu konu üzerinde araştırma yapanlara ve yapacak olanlara ışık tutacaktır. Bu çalışma, zeytin yaprağındaki biyoaktif bileşiklerin sağlık üzerine potansiyel etkilerini incele-mek amacıyla planlanmıştır. A An na ah h t ta ar r K Ke e l li i m me e l le er r: : Zeytin yaprağı; oleuropein; hidroksitirozol, antioksidan A AB BS S T TR RA AC CT T Not only the fruit of the olive tree and the oil obtained from this fruit, but also the olive leaf is also important for human health. Olive oil is used as medicine in the geographies that have been growing since centuries. Today, there are many scientific studies showing the health benefits of olive leaf. There are many phenolic components in the composition of the olive leaf. The most known phenolic compounds identified in extracts of olive leaf are; oleuropein, hy-droxytirozole, verbaskozid, apigenin 7-glucoside and luteloine 7-glucoside. These phenolic compounds attract scientists all over the world and the health benefits of these components on animal and human experiments are reported. These studies generally focus on antioxidant, an-tihypertensive, hypoglycemic, hypocholesterolemic, cardioprotective, anti-inflammatory, an-timicrobial effects. Despite the promising positive effects of olive leaf on health, there are issues such as better understanding of possible interactions between these biologically active ingredients and other nutrients, demonstrating beneficial effects on humans, and determining the optimum dose for use in medical treatment. There is a need for wider and more extensive studies to examine whether the olive leaf extract or olive leaf components are safe at different dosages. More detailed research to help me understand the underlying mechanisms of olive leaf and its phenolic components' therapeutic efficacy will contribute to researchers and those who will do it. This study was planned to investigate the potential effects of bioactive compounds contained in olive leaf on health. K Ke ey yw wo or rd ds s: : Olive leaf; oleuropein; hydroxytyrosol, antioxidant A Ar rt ti ic cl le e i in n P Pr re es ss s
... Numerous crude extracts from plants have been screened to determine their antiviral activity against plant viruses and bioassay guided fractionation of some crude extracts showing inhibitory effect has been extensively studied, which has led to the isolation of many active constituents (Shen et al. 2008). The effect of plant extracts on various human viruses such as HIV, HSV and the influenza virus are well known (Husson et al. 1991;Lee-huang et al. 2003;Schnitzler et al. 2008;Prinsloo et al. 2010;Dunning et al. 2014;Medini et al. 2014;Prinsloo et al. 2018). Additionally, reports of plant extracts of Tanacetum vulgare and Hypericum perforatum against plant viruses, specifically Potato virus Y show potential for the development of natural based pesticides to control plant viruses (Petrov et al. 2015;Petrov et al. 2016a). ...
The tuber necrotic strain of Potato virus Y (PVYNTN) causes widespread disease and has
severe negative effects on the growth and yields of plants, especially those of the Solanaceae
family. The consequences of residual toxicity and non-biodegradation of synthetic chemicals
and pollution of the environment has led to investigations into new non-toxic and
biological treatments to control plant viral diseases. Ethanolic extracts of Bowiea volubilis
(bulbs), Cotyledon orbiculata (leaves), Gomphocarpus fruticosus (leaves), Merwilla plumbea
(dry and fresh bulbs), Nerium oleander (leaves), and the fruits and leaves of Strophanthus
speciosus, were evaluated against PVYNTN in vivo and in vitro. At a concentration of
20 mg · ml−1, ethanolic extracts of Strophanthus speciosus (leaves) and fruits (50 mg · ml−1)
significantly reduced the expression of PVYNTN symptoms on tobacco plants in vitro without
affecting the normal growth and development of the plant. Similarly, at 50 mg · ml−1,
N. oleander, C. orbiculata and B. volubilis (fresh bulbs) and S. speciousus leaves at
20 mg · ml−1 extracts showed significant differences in PVYNTN symptoms in the in vivo
experiment. Strophanthus speciosus leaf and fruit extracts showed significant inhibition in
the in vitro and in vivo assays and demonstrated that S. speciosus has potential to be used as
an antiphytoviral treatment.
... Several compounds in oleuropein are potentially capable of performing antimicrobial activities against fungi, bacteria, as well as mycoplasma (Furneri et al. 2002) and antioxidant activity (Ziogas et al. 2010). Moreover, it was indicated in a research that acute infection and the cell-to-cell transmission of HIV-1 are repressed by oleuropein (Lee-Huang et al. 2003). Due to poor solubility in water and bitter taste, it cannot be used to enrich food. ...
The present study sought to encapsulate oleuropein as a nutraceutical compound in order to investigate its physical properties and stability. We extracted the phenolic compounds of virgin olive leaf by ethanol–water and acetone–water solvents. The purity of this extract was confirmed by analytical high-performance liquid chromatography using oleuropein standard. Oleuropein was encapsulated with different components (lecithin, linoleic acid, glycerol monostearate, soybean oil, and Tween 80), and the effect of their contents on oleuropein-nanostructured lipid carrier (NLC) characteristics was checked by dynamic light scattering test. Moreover, several features of the optimal nanocarrier, including zeta potential, structural, morphology, stability, as well as thermal behavior were studied. The results of optimal NLC exhibited a high zeta potential as well as supreme stability versus aggregation. Thermal study indicated that oleuropein was well embedded into NLCs. The scanning electron microscope images showed that NLC samples had many spherical particles in the form of chain structure. The stable nanocarriers did not exhibit any oleuropein leakage following their analyses for 90 days at − 18, 6, and 25 °C in aqueous suspension.
... In creature tests, specialists watched no lethality in rats, even at high dosages (1g/kg body weight) for seven days (Petkov and Manolov, 1972). In vitro considers on human cell lines found no poisonous quality at 1 mg/ml of concentrate (Lee-Huang et al., 2003). Therefore, the present study was carried out to assess the effects of olive leaves and its extractions by two methods on diabetic rats. ...
... The oil extract from leaves which is considered as an agricultural waste by-product has many potential health benefits such as antioxidant activity [7][8][9][10][11][12], anti-HIV properties [13], anti-proliferative and apoptotic effects [14], protective effect against ...
Background and objectives Finding new uses for by-products of cultivated plants is of great value economically and to the environment. Leaves represent about 10% of the total weight of olives yield. It is worth to obtain value-added products from this material. In this article, the leaves were evaluated chemically and biologically for phenolics and flavonoids as well as for microelements and macroelements and fatty acids. Also, antioxidant and antimicrobial activities were carried out. Materials and methods Air-dried powdered olive leaves were defatted with hexane and the marc was then soaked in 80% methanol and successively extracted with CH 2 Cl 2 , EtOAc, and n-BuOH. Total phenolic and flavonoid contents were determined as chlorogenic acid and rutin equivalents, respectively. Microelements and macroelements were detected in addition to fatty acids. The antioxidant effect was determined in vitro using 1,1-diphenyl-2-picrylhydrazyl and antimicrobial activity was carried out using in-vitro agar well diffusion method. Results and conclusion Total phenolics were found to be highest in the 80% methanolic extract and the lowest in water and ethyl acetate fractions. 1,1-diphenyl-2-picrylhydrazyl-free radical scavenging activity of olive leaf extracts were in this order: 80% methanolic extract, water extract, ethyl acetate fraction and butanol fraction. Also, the calcium : potassium value was 15: 1. Fatty acid profile revealed that linolenic acid was the major fatty acid in terms of percent (49.45%). Ethyl acetate fraction showed positive antibacterial activity and negative antifungal activity whereas water, 80% methanol, and butanol fractions have positive antifungal and negative antibacterial activity. Conclusion Olive leaves could be considered as a potential inexpensive source for food supplements for human health.
... The olive tree known as Olea europaea, and its herbal product famous as olive leaf extract. It was shown a good activity against many diseases (Huang et al., 2003).Much research was mentioned there is an antimicrobial activity of olive oil, and was tested against phytopathogenic microorganisms. It was found that several saltfree solutions from olive oil production processes are rich in antimicrobial compounds, and they have bactericidal and antifungal activity against these microorganisms; and diseases causing them like: influenza, Epstein-Barr virus (EBV), HIV/ARC/AIDS, chronic fatigue, hepatitis B, Candida infections, meningitis, pneumonia, tuberculosis, gonorrhea, malaria, dengue, severe diarrhea, and dental, ear, and urinary tract infections (Eduardo et al., 2013).Polyphenols of olive leaf, especially oleuropein, have interesting effects on the human body such as antioxidant capability, antihypertensive, hypoglycemic, hypocholesterolemic (Patrícia et al., 2015). ...
A long time ago the importance of olive leaf extract was proven in the treatment of many cases that can be caused by viruses, bacteria, fungi and others organisms. And in this study results showed that, all bacteria were resisted to almost antibiotics which used in this study. The antibacterial activity of alcoholic olive leaf extract (OLE) was confirmed with agar well diffusion method and the OLE was had a good antibacterial activity with low concentrations against pathogenic bacteria were used in this study. And MIC, MBC concentrations were showed that OLE had higher concentrations of MIC 30 mg/ml and MBC of 60 mg/ml respectively against Pseudomonas aeruginosa. And lower concentrations of MBC Staphylococcus aureus (MRSA) isolate was sensitive to (OLE) in 15 mg/ml, while MIC was 7.5 mg/ml. The results were showed that all bacteria were used in this study were strong biofilm production, and (OLE) can inhibit biofilm formation in pathogenic bacteria were selected in this study, (p≤ 0.05) .except Escherichia coli the OLE did not have activity against biofilm which produced by this bacteria, p value = (0.2).
... In the large intestine, oleuropein is degraded by the microflora which produces the hydroxytyrosol which expresses biological activity toward large intestinal cells (Corona et al., 2006). Oleuropein has been suggested to have multiple health perspectives such anticancer, cardio-protective, antidiabetic, anti-arrhythmic, immune-stimulant, antiviral, spasmolytic, antiviral, cytostatic, hypotensive, and anti-inflammatory, properties (Al-Azzawie & Alhamdani, 2006;Lee-Huang, Zhang, Huang, & Chang, 2003;Pereira et al., 2007;Ronalli et al., 2006). ...
... Olive leaves are also one of the by-products of olive grove farming; they accumulate during the harvesting of the olive fruit 7,8 . It has been reported in the literature that olive leaves represent a source of polyphenolic compounds with a wide range of physiological properties, such as anti-HIV properties, anti-proliferative and apoptotic effects, lipid-lowering activity, etc. [9][10][11][12][13][14][15][16][17] Many of these properties are due to the antioxidant activity, which can be determined by different mechanisms, such as free radical scavenging, electron or hydrogen atom donation, or metal cation chelation 1 . Furthermore, the health benefits of the olive can also be attributed to the polyphenols present in its leaves 18 . ...
The objective of this work was to evaluate the ability of artificial neural networks (ANN) in near infrared (NIR) spectra calibration models to predict the total polyphenolic content, antioxidant activity, and extraction yield of the olive leaves aqueous extracts prepared with three extraction procedures (conventional extraction, microwave-assisted extraction, and microwave-ultrasound-assisted extraction). Partial least squares (PLS) models were developed from principal component analyses (PCA) scores of NIR spectra of olive leaf aqueous extracts in terms of total polyphenols concentration, antioxidant activity, and extraction yield for each extraction procedure. PLS models were used to view which PCA scores are the best suited as input for ANN based on three output variables. ANN showed very good correlation of NIRs and all tested variables, especially in the case of total polyphenolic content (TPC). Therefore, ANN can be used for the prediction of total polyphenol concentrations, antioxidant activity, and extraction yield of plant extracts based on the NIR spectra.
... Taxifolin (70), also known as dihydroquercetin, is mostly found the stems of Juglans mandshurica, and expressed strong inhibitory activity on the reverse transcriptase enzyme of HIV and thus plays a role in the prevention of HIV replication [292]. From Chrysanthemum morifolium flowers, two important flavonoids apigenin-7-O-β -D-(4′-caffeoyl)glucuronide and glucuronide have been isolated, which exhibited significant activity against the integrase of HIV-1 [293]. Mentha longifolia is another plant whose methanolic extracts are used for the isolation of several therapeutic flavonoids those were found to be active through the same mechanism [294]. ...
Acquired Immunodeficiency Syndrome (AIDS), which chiefly originatesfroma retrovirus named Human Immunodeficiency Virus (HIV), has impacted about 70 million people worldwide. Even though several advances have been made in the field of antiretroviral combination therapy, HIV is still responsible for a considerable number of deaths in Africa. The current antiretroviral therapies have achieved success in providing instant HIV suppression but with countless undesirable adverse effects. Presently, the biodiversity of the plant kingdom is being explored by several researchers for the discovery of potent anti-HIV drugs with different mechanisms of action. The primary challenge is to afford a treatment that is free from any sort of risk of drug resistance and serious side effects. Hence, there is a strong demand to evaluate drugs derived from plants as well as their derivatives. Several plants, such as Andrographis paniculata,Dioscorea bulbifera,Aegle marmelos, Wistaria floribunda, Lindera chunii, Xanthoceras sorbifolia and others have displayed significant anti-HIV activity.Here, weattempt to summarize the main results, which focus on the structures of most potent plant-based natural products having anti-HIV activity along with their mechanisms of action and IC50 values, structure-activity-relationships and important key findings.
... The content of ORP was 39.8 mg ORP/g extract (Table 1) or 95.9 mg ORP/g dry-leaf. These values are in the range of ORP contents reported in the scientific literature for OLE extracts obtained from different cultivars (1.6 mg ORP/g dry-leaf for methanol-water OLE extract, Scognamiglio et al., 2012; 128 mg ORP/g dry-leaf for water OLE extract, Lee-Huang, Zhang, Huang, & Chang, 2003). As for ORP derivatives, the ORP aglycone derivative was found in small concentrations (0.1% of phenolic compounds), indicating that ORP was not degraded during the preparation of the extract (Şahin & Bilgin, 2018). ...
An olive leaf extract (OLE) was microencapsulated with sodium alginate (SA) by spray-drying to study the evolution of oleuropein (ORP) during in vitro gastrointestinal digestion, and its bioaccessibility and potential
bioavailability from OLE and OLE-SA microparticles. Secoiridoids, flavonoids, simple phenols, oleosides and elenolic acid were identified in OLE. OLE/SA ratio 1:1.6 and inlet air temperature 135 °C were the optimal conditions for OLE-SA microparticles. ORP (70%) from OLE was degraded during gastric digestion, giving hydroxytyrosol and ORP-aglycone, whereas only the superficial ORP was released from microparticles. The remaining ORP from OLE was degraded under intestinal conditions, leading to oleosides; whereas alginate was
swollen and disintegrated, releasing the ORP (90% of encapsulated ORP). ORP from both OLE and microparticles was degraded to hydroxytyrosol under colonic conditions. Encapsulation of OLE allowed the protection of ORP under gastric conditions and its controlled release at intestinal conditions, and higher bioaccessibility (58%) and potential bioavailability (20%).
... In the large intestine, oleuropein is degraded by the microflora which produces the hydroxytyrosol which expresses biological activity toward large intestinal cells (Corona et al., 2006). Oleuropein has been suggested to have multiple health perspectives such anticancer, cardio-protective, antidiabetic, anti-arrhythmic, immune-stimulant, antiviral, spasmolytic, antiviral, cytostatic, hypotensive, and anti-inflammatory, properties (Al-Azzawie & Alhamdani, 2006;Lee-Huang, Zhang, Huang, & Chang, 2003;Pereira et al., 2007;Ronalli et al., 2006). ...
... Many studies have shown that olive leaf extract exhibits several activities, such as antioxidant (Ben Salah et al. 2012;Mujić et al. 2011;Lee and Lee 2010), antibacterial (Lee and Lee 2010;Pereira et al. 2007), and antiviral (Lee-Huang et al. 2003) activities. Furthermore, olive leaves possess hypotensive (Somova et al. 2003;Perrinjaquet-Moccetti et al. 2008), neuroprotective (Rabiei et al. 2012), and cardioprotective (Poudyal et al. 2010) properties. ...
In this work, the effect of Détente Instantanée Contrôlée (DIC) (French for instant controlled pressure drop) on the total polyphenol, flavonoids, α-tocopherol contents, and antioxidant activities of olive leaves was studied. Olive leaf extracts were pre-treated at one cycle DIC under 0.1 MPa pressure for 11 s and followed by an extraction with 95% ethanol at 55 °C during 3 h. The phenolic compounds, flavonoïds, oleuropein, and α-tocopherol contents were determined, showing 66.63 mg gallic acid equivalent (GAE)/g db, 12 mg catechin equivalent (CE)/g db, 43.9 mg/g db, and 0.15 mg/g db for the untreated leaves against 239.37 mg GAE/g db, 28 mg CE/g db, 70.3 mg/g db, and 0.59 mg/g db for DIC-treated leaves, respectively. Therefore, DIC allows more availability of bioactive compounds contributing to a high antiradical activity (DPPH) compared to a synthetic antioxidant butylated hydroxytoluene (BHT). Both extracts showed a total antioxidant capacity (method of phosphomolybdenum) greater than that of the standard BHT. Likewise, both extracts have a reducing power (FRAP test) significant concentration-dependent. The DIC-treated leaves showed a higher antioxidant capacity compared to that of untreated leaves. Thus, DIC could be an effective treatment to promote the extraction of bioactive molecules of high antioxidant activities from olive leaves.
... In recent years, the presence of immunomodulator substances in the olive plant has been reported by researchers. 33,34 The study conducted by Rosignoli (2012) revealed that the phenolic compounds of the olive extract are able to stimulate human monocytes exposed to LPS in vitro and increase TNFα production. 33 The study showed that few hours following the exposure to L. major, peritoneal macrophages presented a predominantly Th2 response. ...
This study aimed to identify the effects of olive leaf extract (OLE) on IFNγ, TNFα, TGFβ, and nitric oxide (NO) resulted from macrophages infected with Leishmania major (L. major) amastigotes in the culture medium. High-performance liquid chromatography (HPLC) was used to analyze the level of Oleuropein in plant extract. To evaluate the immunomodulatory effects of OLE, the isolated BALB/c mice peritoneal macrophages were infected with L. major promastigotes and treated with 6.25, 12.5, and 25μg/mL concentrations of OLE. To assess the cytokines, supernatants of cell cultures were harvested after 12, 24, and 48 h. Cytokine production was evaluated by ELISA. Nitrite accumulation in the culture medium was assessed using the Griess reaction. The level of Oleuropein in the extract was 18.45% by HPLC. According to results, the production of IFNγ and TNFα was significantly increased when the infected and/or not infected macrophages with L. major promastigotes were affected by different concentrations of OLE. Conversely, the production of TGFβ was significantly decreased under the same conditions. Furthermore, the colorimetric determination of NO accumulation in the culture medium indicated that OLE has no effect on NO production. The study corroborates the immunomodulatory effects of OLE on L. major-infected macrophages.
... (w/w) L7G [26]. Lee-Huang et al. reported 12.8 % (w/w) oleuropein in aqueous extract of O. europaea leaves [27]. In another study by Altınyay and Altun, oleuropein values in methanolic extracts of O. europaea var. ...
In this study, qualitative and quantitative analysis of commercially available food supplements composed of olive leaf extract and herbal tea products containing olive leaf were evaluated by High-Performance Thin-Layer Chromatography (HPTLC) and a newly developed and validated High-Performance Liquid Chromatographic (HPLC) method for their quality assessment. In addition, leaves of two varieties of Olea europaea L. (var. europaea and var. sylvestris) grown in Turkey which were assigned as reference plant materials and their chemical compositions were also comparatively analyzed by HPTLC. Then HPTLC fingerprints of reference plant materials were compared to the marketed olive leaf samples. For quantification of oleuropein and luteolin 7-O-glucoside (L7G) contents in the samples, a simple and fast HPLC method was developed and validated. Consequently, in water and hydroalcoholic extracts of O. europaea var. europaea leaves, oleuropein contents were found to be 15.89% (w/w) and 15.84% (w/w), while L7G contents were 0.75% and 1.23%, respectively. For the reference materials, oleuropein in O. europaea L. var. sylvestris leaves was found to be 12.77% (w/w, in water extract) and 12.36%(w/w, in hydroalcoholic extract), while the concentration of L7G was 0.51% (w/w) and 0.83% (w/w) in water and hydroalcoholic extracts, respectively. Qualitative analysis of the commercial products revealed that fraud was detected in three of eight olive leaf herbal tea bag brands and two of ten olive leaf food supplements. These samples were found either devoid of oleuropein or they had different HPTLC fingerprint profiles than the reference samples.
... The extracts made from olive leave are also studied for their antiviral activity against viral hemorrhagic virus septicaemia (VHSV) [35] and against HIV-1 infection and replication. Cell-to-cell transmission of HIV was inhibited in an in a dose-dependent manner, and HIV replication was inhibited in an in vitro experiment [36]. Oleuropein compounds has been patented for antiviral activity against viral disease, including herpes, mononucleosis and hepatitis [37]. ...
... The olive Olea europaea L. is an important evergreen fruit tree worldwide, especially in the Mediterranean Basin area. It is grown due to the high nutritional, industrial and health values of olive fruits (Huang et al, 2003). Olive leaf extract contains phenolic compounds which are effective against bacteria, mycoplasma and yeasts. ...
The inhibitory activity of polyphenolic compounds extracted from olive leaves was tested against F. oxysporum f. sp. niveum growth. Results showed phenolic and alcoholic extracts inhibited fungal growth by 70.6% and 66.75%, respectively, at 4000 ppm concentration. Olive leaves powder inhibited the growth by 47.50%. All treatments increased watermelon germination percentage after 7 days when scored 85% and 100% at 0.4% and 0.8% olive leaf powder concentrations, respectively. Alcoholic treated seeds at 4000 ppm scored 90% compared to pathogenic fungus treatment with 25% germination percent. Whereas the germination percentages were 90% and 100%, respectively for fungicide (Bltanol) and healthy control (untreated) treatments. All treatments could protect watermelon seedlings for continuous 35 days after planting. The phenolic extract showed the highest vigour index values when scored 1616.7 and 1821.6 at the concentrations of 4000 and 8000 ppm, respectively. Whereas, alcoholic extract and olive leaf powder at scored 1332 and 1102.5 at concentration 8000 ppm and 0/8% respectively, compared to the pathogenic fungal and the fungicidal treatments with 360.5 and 896.8, respectively. These results indicated the effectiveness of the olive leaf extract in fungal growth inhibition. This study confirmed the presence of antifungal active substances in olive leaves against pathogenic fungi.
... Received 9 February 2020; Received in revised form 26 June 2020; Accepted 29 June 2020 compound in olive leaf extracts (Bouaziz and Sayadi, 2005;Ozdemir et al., 2014). These phenolic compounds possess antioxidant, antimicrobial, antiviral, anti-atherogenic, cardioprotective, antihypertensive and anti-inflammatory properties (Khalatbary and Zarrinjoei, 2012;Lee-Huang et al., 2003;Ranalli et al., 2006). Furthermore, these compounds have hypocholesterolemic and hypoglycemic activities (Hadrich et al., 2016) and improve lipid metabolism minimizing obesity problems (Jimenez-Sanchez et al., 2017). ...
Olive leaves are important olive by-products due to their high content of phenolic compounds and elenolic acids, which possess antioxidant, antimicrobial, anti‐atherogenic and anti‐inflammatory properties, among others. Thus, pressurized liquid extraction was used to obtain a high recovery of these compounds from olive leaves. A Box-Behnken design was performed to optimize the PLE conditions of temperature (50−200 °C), % ethanol-water (0–100 %) and extraction time (5−20 min) in order to obtain the highest content of simple phenols, secoiridois, flavonoids, elenolic acids, total compounds and extraction yield from olive leaves. Olive leaf extracts were analyzed by high performance liquid chromatography coupled to mass spectrometry (HPLC-MS). The highest content of total compounds was 158.7 ± 0.4 mg g⁻¹ d.w obtained at 105 °C, 100 % ethanol and 5 min, whereas the highest extraction yield was 43 ± 3% obtained at 198 °C, 100 % ethanol and 5 min. Therefore, multi-response analysis was carried out using desirability function to optimize the PLE conditions for both total compounds and yield. These optimal conditions were 138 °C, 100 % EtOH and 5 min obtaining 144 mg g⁻¹ d.w. of total compounds and 42.2 % of yield. The optimal temperature of 138 °C has shown a great phenolic recovery and 100 % ethanol has been shown to be a safe solvent to use in the food industry. In addition, short extraction times (5 min) mean lower energy consumption and lower costs. Therefore, these PLE optimum conditions could be implemented on an industrial scale.
... After extraction, insoluble material was removed using Whatman No. 1 filter paper. The filtrates were then concentrated at 50°C to yield a dark brown solid extract, with references to the powdered samples; the yields of the OLE were 3.59 g, and extracts were stored in the refrigerator for rat supplementation (Lee-Huang et al. 2003;Al-Attar and Abu Zeid 2013;Wulandari et al. 2016). ...
Lead acetate (PbAc) is one of the toxic metals in the environment which causes many effects on different organs of the body. And due to the importance of the olive tree, with its healthy and protective elements against many diseases, the leaf extract of this tree was chosen in our study. Therefore, the aim of this study was to investigate the role of olive leaf (Olea europea L.) extract (OLE) against PbAc-induced sperm toxicity, sex hormone changes, oxidative stress, and histopathological changes in rats. Twenty male Wistar rats were divided into four groups (group 1, as control; group 2, OLE; group 3, PbAc; group 4, PbAc+OLE). In the PbAc group, the body weight, testis and epididymis weights, sexual hormones, sperm characteristics, GR, GPx, GST, GSH, SOD, and CAT were significantly decreased, and the sperm abnormality and TBARS level were significant increase when compared with control and OLE groups. Also, numerous damages to testicular tissue were observed in the PbAc group when compared to the control group, while the treatment with OLE in the fourth group led to improvement of sex hormones, semen characteristics, oxidative stress, and testicular tissue damage caused by PbAc. It can be concluded that OLE has a protective and ameliorative effects against PbAc-induced oxidative stress, apoptosis and alterations in testicular tissue, and sperm quality in rats.
... Olive and its components do not possess toxicity to humans. An animal model study conducted by Lee-Huang, Zhang, and Huang (2003) reported that an administration of 1 g/kg bw for 7 days did not cause toxicity to the rats. In another in vitro human cell toxicity study, it was also confirmed that OL extract (1 mg/ml) was not toxic to human cell lines (Petkov & Manolov, 1972). ...
Noncommunicable diseases have increasingly grown the cause of morbidities and mortalities worldwide. Among them, cardiovascular diseases (CVDs) continue to be the major contributor to deaths. CVDs are common in the urban community population due to the substandard living conditions, which have a significant impact on the healthcare system, and over 23 million human beings are anticipated to suffer from the CVDs before 2030. At the moment, CVD physicians are immediately advancing both primary and secondary prevention modalities in high-risk populations. The cornerstone of CVD prevention is a healthy lifestyle that is more cost-effective than the treatments after disease onset. In fact, in the present scenario, comprehensive research conducted on food plant components is potentially efficacious in reducing some highly prevalent CVD risk factors, such as hypercholesterolemia, hypertension, and atherosclerosis. Polyphenols of olive oil (OO), virgin olive oil (VOO), and extra virgin olive oil contribute an essential role for the management of CVDs. Olive oil induces cardioprotective effects due to the presence of a plethora of polyphenolic compounds, for example, oleuropein (OL), tyrosol, and hydroxytyrosol. The present study examines the bioavailability and absorption of major olive bioactive compounds, for instance, oleacein, oleocanthal, OL, and tyrosol. This review also elucidates the snobbish connection of olive polyphenols (OP) and the potential mechanism involved in combating various CVD results taken up from the in vitro and in vivo studies, such as animal and human model studies.
... It was shown in this study, that OLE treatment can also reverse many of these HIV infection-induced changes. In the effective dose range, no OLE toxicity on uninfected target cells were reported in this study 43 . ...
Olive tree (Olea europaea L.) is an evergreen plant, cultivated ever since ancient times and has widely been used in traditional medicine. Mediterranean diet, rich in olive and its derivatives has been associated with a lower incidence of cardiovascular diseases, cancer, inflammation and stroke. In addition to olive and its oil, olive leaf and its various beneficial properties has lately been drawing the attention of many researchers. It has been postulated that many of the beneficial effects of OLE root from the strong antioxidant effects, exerted majorly by components such as oleuropein and hydroxytyrosol. Many considerable health-benefits of olive leaf extract (OLE) have been described in the literature, such as the effects on cardiovascular system, anticancer effects, antimicrobial effects, hypoglycemic effects and so on. In this study the antioxidant effects and some of the other health-benefitting effects of OLE are reviewed
... Also, it had been found that Olive leaves inhibits acute infection and cell-tocell transmission of HIV-1 and additionally inhibits HIV-1 replication. [10]. The major active elements in olive leaf is oleuropein (see Fig.1 a) and its derivatives, like hydroxytyrosol and tyrosol, additionally as cafeic acid, p-coumaric acid, vanillic acid, vanillin, luteolin, diosmetin, rutin, luteolin-7glucoside, apigenin-7-glucoside, and diosmetin-7- [11]. ...
Olive tree (Olea Europea L.) is one of the most important crops in the Mediterranean countries. The global olive oil industry annually generates many tons of olive leaves as waste. The present study aims at a valorisation of Algerian olive leaves harvested from the region of Bouira for therapeutic use. In order to evaluate the biological effects of the wild olive tree, chemical characterization tests of the leaves were carried out in the Natural Substances Laboratory of Saidal group according to their validated protocols drawn from the French pharmacopoeia. A phytochemical screening has been realized and whose purpose is to refer to the extraction, screening and identification of the medicinally active substances in the plant. Different extractions have been carried out in several solvents in order to extract bioactive molecules from the leaves using several solvents. Subsequently, a pharmacological characterization has been completed by determining the following: antioxidant activity of the extracts was evaluated in vitro by the DPPH method, anti-inflammatory activity was studied in vivo by induction of carrageenan oedema; the antibacterial activity was achieved by the agar medium diffusion method. Finally, we formulated an anti-inflammatory and antibacterial ointments based on the results obtained.
Stable oleuropein-coated gold nanoparticles in aqueous media were synthesized for the first time. Oleuropein (OLE) concentration in the reaction medium was found to greatly influence the outcome and stability of the resulting nanocolloid, with a marked decrease in particle size being found for the more concentrated oleuropein solutions. The protection mechanisms involved in the stabilized nanosystems were analyzed. Oleuropein self-assembled structures were found to be formed at a concentration threshold of [OLE] > 5 × 10−5 M, and observed through the use of CryoSEM imaging. Those structures were responsible for both the increased stability and the decrease in size observed at the more concentrated solutions.
The purpose of this research was to study the effect of microwave drying (MD) on the major phenolic compound oleuropein, total phenolic and flavonoid contents, and antioxidant activity of the olive leaves. The results were compared to those obtained after using freeze drying (FD), vacuum drying (VD), oven drying (OD), and ambient air-drying (AAD). Response surface methodology, using a central composite face-centerd design, was used to optimize the effects of microwave irradiation power (300–500 W), solid mass (1.5–2.5 g), and drying time (4–6 min) on oleuropein and other olive leaves antioxidant compounds. The second-order models were found highly adequate with very low root mean squared deviation (RMSD) and high coeffecient of determination (R2) values. The results of MD under optimum conditions (2.085 g sample at 459.257 W for 6 min of drying period) has demonstrated to be the best drying method followed by FD, VD, OD, and AAD. Olive leaves are agricultural waste which contains significant amounts of valuable compounds such as oleuropein and phenolic compounds. Nowadays, application of these compounds has attracted considerable interest as food additives and/or nutraceuticals in both food and pharmaceutical industries. Several methods have been applied for the extraction of phenolic compounds from olive leaves and by-products. However, to obtain higher extraction yield, it is important to reduce the water content of the samples before extraction. This study demonstrates the feasibility of using microwave drying as a promising technique compared to other methods (e.g., freeze-, vacuum-, oven-, and ambient air-drying) for drying of olive leaves with minimum changes in total phenolic, flavonoids, antioxidant activity, and oleuropein contents.
Viral infections are being managed therapeutically through available antiviral regimens with unsatisfactory clinical outcomes. The refractory viral infections resistant to available antiviral drugs are alarming threats and a serious health concern. For viral hepatitis, the interferon and vaccine therapies solely are not ultimate solutions due to recurrence of hepatitis C virus. Owing to the growing incidences of viral infections and especially of resistant viral strains, the available therapeutic modalities need to be improved, complemented with the discovery of novel antiviral agents to combat refractory viral infections. It is widely accepted that medicinal plant heritage is nature gifted, precious, and fueled with the valuable resources for treatment of metabolic and infectious disorders. The aims of this review are to assemble the facts and to conclude the therapeutic potential of medicinal plants in the eradication and management of various viral diseases such as influenza, human immunodeficiency virus (HIV), herpes simplex virus (HSV), hepatitis, and coxsackievirus infections, which have been proven in diverse clinical studies. The articles, published in the English language since 1982 to 2017, were included from Web of Science, Cochrane Library, AMED, CISCOM, EMBASE, MEDLINE, Scopus, and PubMed by using relevant keywords including plants possessing antiviral activity, the antiviral effects of plants, and plants used in viral disorders. The scientific literature mainly focusing on plant extracts and herbal products with therapeutic efficacies against experimental models of influenza, HIV, HSV, hepatitis, and coxsackievirus were included in the study. Pure compounds possessing antiviral activity were excluded, and plants possessing activity against viruses other than viruses in inclusion criteria were excluded. Hundreds of plant extracts with antiviral effect were recognized. However, the data from only 36 families investigated through in vitro and in vivo studies met the inclusion criteria of this review. The inferences from scientific literature review, focusing on potential therapeutic consequences of medicinal plants on experimental models of HIV, HSV, influenza, hepatitis, and coxsackievirus have ascertained the curative antiviral potential of plants. Fifty-four medicinal plants belonging to 36 different families having antiviral potential were documented. Out of 54 plants, 27 individually belong to particular plant families. On the basis of the work of several independent research groups, the therapeutic potential of medicinal plants against listed common viral diseases in the region has been proclaimed. In this context, the herbal formulations as alternative medicine may contribute to the eradication of complicated viral infection significantly. The current review consolidates the data of the various medicinal plants, those are Sambucus nigra, Caesalpinia pulcherrima, and Hypericum connatum, holding promising specific antiviral activities scientifically proven through studies on experimental animal models. Consequently, the original research addressing the development of novel nutraceuticals based on listed medicinal plants is highly recommended for the management of viral disorders.
The highest total phenol contents were found in olive leaves heated in microwave 540 W and athmospheric air. While the antioxidant activity of olive leaves heated in microwave 180 W change between 76.99% (Akdeniz Yerli) and 82.26% (Sarı Ulak), antioxidant activity values of leave samples heated in microwave 360 W varied between 81.20% (Yağlık) and 82.24% (Gemlik). The highest p‐coumaric acid (161.92 mgGAE/100g) and trans‐ferulic acid (3,276.09 mg GAE/100g) were determined in Akdeniz yerli olive leaves dried in microwave 360 W. In addition, the highest oleuropein content (1,104.66 mg GAE/100g) was found in Akdeniz yerli olive leaves in control group. The Ca contents of olive leaves dried in microwave 540 W vary between 12,300.34 mg/kg (Akdeniz Yerli) and 16,437.52 mg/kg (Sarı ulak), Ca contents of olive leaves dried in oven (70 °C) were changed between 10,188.19 mg/kg (Akdeniz yerli) and 16,801.42 mg/kg (Sarı ulak) (p < .05).
Practical application
Olive oil is important for economic value. But, recently olive leaves were used as a medicinal plant in an infusion or decoction forms. Because, oleuropein is a phenolic compound of olive leave and its useful for human health. The best known oleuropein source is olive leaf. Drying process was affected on change of chemical and bioactive properties of plant materials. The drying process is important not only for the preservation of vegetable materials but also for the preservation of the nutritional value and the functional properties without deterioration.
Owing to the richness of bioactive compounds, Olea europea leaf extracts exhibit a range of health effects. The present research evaluated the antibacterial and antiviral effect of leaf extracts obtained from Olea europea L. var. sativa (OESA) and Olea europea var. sylvestris (OESY) from Tunisia. LC-DAD-ESI-MS analysis allowed the identification of different compounds that contributed to the observed biological properties. Both OESA and OESY were active against Gram-positive bacteria (MIC values between 7.81 and 15.61 μg/mL and between 15.61 and 31.25 μg/mL against Staphylococcus aureus ATCC 6538 for OESY and OESA, respectively). The antiviral activity against the herpes simplex type 1 (HSV-1) was assessed on Vero cells. The results of cell viability indicated that Olea europea leaf extracts were not toxic to cultured Vero cells. The half maximal cytotoxic concentration (CC50) values for OESA and OESY were 0.2 mg/mL and 0.82 mg/mL, respectively. Furthermore, both a plaque reduction assay and viral entry assay were used to demonstrate the antiviral activity. In conclusion, Olea europea leaf extracts demonstrated a bacteriostatic effect, as well as remarkable antiviral activity, which could provide an alternative treatment against resistant strains.
In recent years, a remarkable increase in olive oil consumption has occurred worldwide, favoured by its organoleptic properties and the growing awareness of its health benefits. Currently, olive oil production represents an important economic income for Mediterranean countries, where roughly 98% of the world production is located. Both the cultivation of olive trees and the production of industrial and table olive oil generate huge amounts of solid wastes and dark liquid effluents, including olive leaves and pomace and olive oil mill wastewaters. Besides representing an economic problem for producers, these by-products also pose serious environmental concerns, thus their partial reuse, like that of all agronomical production residues, represents a goal to pursue. This aspect is particularly important since the cited by-products are rich in bioactive compounds, which, once extracted, may represent ingredients with remarkable added value for food, cosmetic and nutraceutical industries. Indeed, they contain considerable amounts of valuable organic acids, carbohydrates, proteins, fibers, and above all, phenolic compounds, that are variably distributed among the different wastes, depending on the employed production process of olive oils and table olives and agronomical practices. Yet, extraction and recovery of bioactive components from selected by-products constitute a critical issue for their rational valorization and detailed identification and quantification are mandatory. The most used analytical methods adopted to identify and quantify bioactive compounds in olive oil by-products are based on the coupling between gas- (GC) or liquid chromatography (LC) and mass spectrometry (MS), with MS being the most useful and successful detection tool for providing structural information. Without derivatization, LC-MS with electrospray (ESI) or atmospheric pressure chemical (APCI) ionization sources has become one of the most relevant and versatile instrumental platforms for identifying phenolic bioactive compounds. In this review, the major LC-MS accomplishments reported in the literature over the last two decades to investigate olive oil processing by-products, specifically olive leaves and pomace and olive oil mill wastewaters, are described, focusing on phenolics and related compounds.
Hydroxytyrosol (4-(2-hydroxyethyl)-1,2-benzenediol) is the most known bioactive compound from the plant Olea europaea (olive tree). To date, few biocatalysis processes allowing efficient production of hydroxytyrosol from potential substrates including, tyrosol (2-(4-hydroxy) phenyl ethanol) and tyrosine have been reported. In this paper, we report for a Gram-positive bacterium that produces hydroxytyrosol via conversion of tyrosol and/or L-tyrosine, identified as a Rhodococcus pyridinivorans based on phenotypic characteristics and 16S rDNA sequence, and designated R. pyridinivorans strain 3HYL DSM109178. Interestingly, strain 3HYL shows an outstanding production of hydroxytyrosol from tyrosol up to 16.4 ± 0.23 mmol/L with high kinetic parameters exceeding the reported values. However, a slight downstream metabolism of the product is assigned to the wild-type strain during the stationary phase of growth. The plasmid-cured strain was obtained using random chemical mutagenesis, designated R. pyridinivorans 3HYL-AO, and was able to produce hydroxytyrosol, with yields up to 21.75 ± 0.34 mmol/L. Moreover, the plasmid-cured strain exhibited a significant reduction in the transformation to its acetic acid forms compared to the wild-type strain as depicted by HPLC analysis. Comparison of kinetic data of the bioconversion/accumulation process between the wild type and mutant strain, in the presence and absence of L-tyrosine, and thus suggesting the occurrence of an upstream pathway for synthesis of tyrosol via (L)-tyrosine.
Olive leaf as an agricultural waste contains valuable bioactive compounds that are mainly used for pharmaceutical and cosmetic industries. Lately the major component, oleuropein, has gained extra attention due to the anti-viral activity against SARS-CoV-2 that causes Coronavirus disease (Covid-19). In this study, extraction of the bioactive compounds from olive leaves was conducted using a non-conventional and green method. New generation green solvents, natural deep eutectic solvents (NADES) were used in combination with ultrasound assisted extraction. Screening of NADES type, temperature, and particle size were investigated using one-pot-at-a-time method while, NADES amount and liquid-to-solid ratio were optimized using experimental design. The results were evaluated in terms of total polyphenol yield (YTP), total flavonoid yield (YTF) and antiradical activity (AAR). At the optimized conditions, the highest total polyphenol yield and the highest total flavonoid yield were achieved with choline chloride–fructose–water (CFW) (5:2:5) as 187.31 ± 10.3 mg gallic acid equivalent g⁻¹ dw and 12.75 ± 0.6 mg apigenin equivalent g⁻¹ dw, respectively. The extracts were also analyzed for oleuropein, caffeic acid and luteolin contents. The highest amount of oleuropein and caffeic acid were extracted by glucose–fructose–water (GFW) (1:1:11) as 1630.80 mg kg⁻¹ dw and 112.77 mg kg⁻¹ dw, respectively.
Graphic Abstract
Lipopolysaccharide (LPS)-induced activation of murine RAW 264.7 cells results in the production of pro-inflammatory cytokines including PGE2, IL-6, TNF-a, and IL-1β. In this study, we investigated the anti-inflammatory effects of the Olea europaea extract from Jeju island using LPS which induces an inflammatory response. To examine the potential anti-inflammatory properties of the Olea europaea extract, we measured the amount of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β on RAW 264.7 cells after the Olea europaea extract treatment. The Olea europaea extracts showed higher anti-inflammatory activity by inhibiting the production of PGE2, NO, TNF-α, IL-6, and IL-1 induced by LPS stimulation in RAW 264.7 cells. Also, Olea europaea extracts decreased mRNA expression of iNOS, and COX-2. There was no cytotoxicity in the macrophage proliferation treated with the Olea europaea extract compared to the control in the LDH assay. These results suggest that the Olea europaea extract may exert significant effects on inflammatory factors and be a potential source as a new natural anti-inflammatory agent. Further investigations will focus on cell-based in vitro assays and in chemically identifying the major active components mediating the anti-aging and anti-inflammation responses. © The Korean Society of Food Preservation. All rights reserved.
Dietary components, olive oil and its fractions, are capable to effect on immune network and their mechanisms. Olive oil is a principal source of dietary lipids and polyphenols in the Mediterranean diet, which is especially relevant in the case of extra-virgin olive oil (VOO) and also in VOO. They can effect cytokine production, signaling pathways, and overall health status. This chapter summarizes the key works of olive and olive oil fractions on immune system and several immune-mediated diseases.
It is known that the Mediterranean diet is effective in reducing the risk of several chronic diseases, including cancer. A critical component of the Mediterranean diet is olive oil, and the relationship between olive oil consumption and the reduced risk of cancer has been established. Oleuropein (OL) is the most prominent polyphenol component of olive fruits and leaves. This compound has been shown to have potent properties in various types of cancers, including breast cancer. In the present study, the molecular mechanism of OL was examined in two racially different triple-negative breast cancer (TNBC) cell lines—African American (AA, MDA-MB-468) and Caucasian American (CA, MDA-MB-231). The data obtained showed that OL effectively inhibits cell growth in both cell lines, concomitant with S-phase cell cycle arrest-mediated apoptosis. The results also showed that OL-treated MDA-MB-468 cells were two-fold more sensitive to OL antiproliferative effect than MDA-MB-231 cells were. At lower concentrations, OL modified the expression of many apoptosis-involved genes. OL was more effective in MDA-MB-468, compared to MDA-MB-231 cells, in terms of the number and the fold-change of the altered genes. In MDA-MB-468 cells, OL induced a noticeable transcription activation in fourteen genes, including two members of the caspase family: caspase 1 (CASP1) and caspase 14 (CASP14); two members of the TNF receptor superfamily: Fas-associated via death domain (FADD) and TNF receptor superfamily 21 (TNFRSF21); six other proapoptotic genes: growth arrest and DNA damage-inducible 45 alpha (GADD45A), cytochrome c somatic (CYCS), BCL-2 interacting protein 2 (BNIP2), BCL-2 interacting protein 3 (BNIP3), BH3 interacting domain death agonist (BID), and B-cell lymphoma/leukemia 10 (BCL10); and the CASP8 and FADD-like apoptosis regulator (CFLAR) gene. Moreover, in MDA-MB-468 cells, OL induced a significant upregulation in two antiapoptotic genes: bifunctional apoptosis regulator (BFAR) and B-Raf proto-oncogene (BRAF) and a baculoviral inhibitor of apoptosis (IAP) repeat-containing 3 (BIRC3). On the contrary, in MDA-MB-231 cells, OL showed mixed impacts on gene expression. OL significantly upregulated the mRNA expression of four genes: BIRC3, receptor-interacting serine/threonine kinase 2 (RIPK2), TNF receptor superfamily 10A (TNFRSF10A), and caspase 4 (CASP4). Additionally, another four genes were repressed, including caspase 6 (CASP6), pyrin domain (PYD), and caspase recruitment domain (CARD)-containing (PAYCARD), baculoviral IAP repeat-containing 5 (BIRC5), and the most downregulated TNF receptor superfamily member 11B (TNFRSF11B, 16.34-fold). In conclusion, the data obtained indicate that the two cell lines were markedly different in the anticancer effect and mechanisms of oleuropein’s ability to alter apoptosis-related gene expressions. The results obtained from this study should also guide the potential utilization of oleuropein as an adjunct therapy for TNBC to increase chemotherapy effectiveness and prevent cancer progression.
According to many reports, phenolic compounds isolated from olive leaves have very good biological activities, especially antimicrobial. Presently, the resistance of microorganisms to antibiotics is greater than ever. Therefore, there are numerous recent papers about alternative solutions for inhibiting their influence on human health. Olive leaf is studied as an important source of antimicrobials with low cost and used in medicine. Numerous publications on involving green technologies for isolation of active compounds from olive leaves have appeared over the past few decades. The present review reports on current knowledge of the most isolated phenolic compounds from olive leaf extract as well as methods for their isolation and characterization. This paper uses recent research findings with a wide range of study models to describe the antimicrobial potential of phenolic compounds. It also describes the vast range of information about methods for determination of antimicrobial potential focusing on effects on different microbes. Additionally, it serves to highlight the role of olive leaf extract as an antioxidants and presents methods for determination of antioxidant potential. Furthermore, it provides an overview of presence of enzymes. The significance of olive leaves as industrial and agricultural waste is emphasized by means of explaining their availability, therapeutic and nutritional effects, and research conducted on this field.
Background: Olive tree leaves ( Olea europaea ) are widely used in traditional medicine in the Mediterranean Region. Interest in the olive leaf and its chemical constituents has recently been increasing. Its benefits, however, have been known for centuries, and it has been traditionally used to prevent and treat different diseases. The aim of this study was the determination of antimicrobial, antioxidant activities and anti-EBV effects of olive leaves. Methods : The present study was focused on extraction of leaves of olea europea cultivated and wild type from two different geographical tunisian zone: Sfax and El Kef, and the determination of antimicrobial activities against Gram- and Gram+ bacteria and fungi. Olive leaves was analyzed for antioxidant power in chemical system by the DPPH test and the chemiluminescence and in biological system by lipid peroxydation tests (MDA and DC) in Raji cells lines. The antiviral (anti-EBV) effects of olive leaves were assessed using indirect immunofluorescence technique. Results: The antioxidant effect was studied by chemiluminescence where a significant decrease on reactive oxygen species production was observed after leaves olive extract treatment. Antioxidant activities were studied by direct reactive oxyden species assay using chemical systems. The results very interesting for both wild type and cultivated in the two regions since we obtained IC50s of the order of 20.79 μg / ml (cultivated sfax) with DPPH scavening radical. The best result obtained when used olive leaves extract cultivated from Sfax. Our results showed a protection against oxidative stress, highlighted by a significant decrease in MDA and DC levels (p <0.05). Also, a significant antiviral effect of leaves of olive cultivated in Sfax against Epstein-Barr virus (EBV) was determined. Conclusion: The olive leaves extracts analyzed in this work showed a potent antimicrobial activity, an antioxidant activity was expressed by a significant decrease in the production of ERO in the Raji cell line and an anti-EBV effect.
The interactive effects of cultivar, collecting period, and geographical location on the content and composition of biophenols and macro and micronutrients in olive (Olea europaea L.) leaf were investigated. Leaves of six cultivars were collected at three periods in two locations in Croatia. The leaves of Istarska bjelica cultivar had the greatest biophenol (oleuropein) potential, especially those sampled in January and in March at the location of Pag. All the cultivars yielded leaves with the highest concentration of biophenols in March, which coincided with the pruning period. Except for high oleuropein concentration in Istarska bjelica, flavonoids were found to be most useful for differentiating olive leaves according to cultivar. Verbascoside turned out to be the most potent differentiator of collecting periods, while phosphorus and zinc turned out to be most useful for differentiating locations. Despite different agroecological conditions at the two locations, cultivar exhibited a significant effect on olive leaf nutrient composition, which was certainly causally related to that of the biophenols. The results obtained showed that it is possible to plan more well-timed and efficient exploitation of biophenols from olive leaf based on the knowledge about the interactive effects of the three studied factors.
Purpose
The aim of this study was to evaluate the effects of oleuropein radiation protection and to find an effective radioprotector.
Materials and Method
Human mononuclear cells were treated with oleuropein at the concentration of 100 μM (optimum concentration), incubated for 24 h, and then exposed to 2 Gy gamma-rays. The anti-radiation effect of oleuropein was assessed by MTT assay, flow cytometry, comet assay, and micronucleus (MN) assay.
Results
It was found that pretreatment with oleuropein (25, 50, 75, 100, 200, 400, and 800 nM, and 1, 5, 10, 15, 20, 25, 30, 40, 50, 75, 100, 125, 150, 175, and 200 µM) significantly increased the percentage of cell viability compared to the irradiated group (p < .001). Moreover, oleuropein treatment with the above concentrations defined without gamma-ray did not show any cytotoxicity effect in human mononuclear cells. The LD50/24h dose was calculated as 2.9 Gy, whereas by 200, 150, 50, and 100 µM oleuropein prior to radiation (1, 2,and 4 Gy), radiation LD50/24h increased to 3.36, 3.54, 3.81, and >4 Gy, in that order. A very noticeable dose-modifying factor (DMF) of 1.16, 1.23, 1.31, and 1.72 was observed for 200, 150, 50, and 100 µM, in order. Therefore, 100 µM of oleuropein was selected as the desirable dose for radio-protection trial, and 2 Gy gamma-rays were used for further research. Human mononuclear cells treatment with oleuropein (100 µM) prior to 2 Gy gamma-rays significantly decreased apoptosis, genomic damage, and MN occurrence in human mononuclear caused by gamma-radiation (p < .001). Furthermore, treatment with oleuropein (100 µM) without radiation did not lead to apoptosis, genotoxicity, or clastogenic effects caused by oleuropein in human mononuclear cells.
Conclusion
The results revealed that oleuropein is able to significantly reduce cytotoxicity, apoptosis, genotoxic, and clastogenic effects of gamma-rays.
The effect of harvest periods on total phenol, antioxidant activity, individual phenolic compounds of fruit and leaves of Tavşan Yüreği, Memecik, Edremit, Ayvalık and Gemlik olive varieties grown in Turkey were investigated. The highest total phenol (317.70 mg/100 g and 2657.81 mg/100 g) were observed in Tavşan Yüreği olive fruit and Ayvalık leaves harvested in December, respectively. The highest antioxidant activities (83.84%) were determined in Edremit fruit harvested in August and 83.33% in either Edremit olive leaves harvested in November and Tavşan Yüreği leaves harvested in December. The olive fruit contained gallic acid ranging from 7.18 mg/100 g (August) to 35.85 mg/100 g (December) in case of Ayvalık and 2.09 mg/100 g (November) to 21.62 mg/100 g (December) in Edremit. Gemlik olives showed higher gallic acid contents compared to the other varieties, however it depended significantly on harvest time in all cases. 3,4-Dihydroxybenzoic acid contents ranged from 33.11 mg/100 g (October) to 25.17 mg/100 g (September) in Memecik olives; 12.17 mg/100 g (August) to 33.11 mg/100 g (December) in case of Tavşan Yüreği olives depending on harvest time. The 3,4-dihydroxybenzoic acid contents of Memecik leaves ranged between 122.25 mg/100 g (September) to 196.58 mg/100 g (August) and that of Tavşan Yüreği leaves changed between 99.38 mg/100 g (November) and 179.90 mg/100 g (August). The leaves of these two varieties contained significantly (p < 0.01) higher 3,4-dihydroxybenzoic acid contents than other varieties. The highest gallic acid (144.83 mg/100 g) was detected in Memecik leaves (September) whereas lowest were found in Gemlik leaves collected in October.
Viral infections, in particular infections associated with hepatitis A, B, and C viruses, human immunodeficiency virus, and emerging and chronic viruses, such as Covid-19, have challenged human survival. As a result, the discovery of new antiviral drugs is of great importance. In this regard, the use of medicinal plants can be considered a useful method in the treatment of these diseases, because medicinal plants have been used for centuries to treat various diseases almost anywhere in the world. They offer features such as high chemical diversity, lower production costs, and milder side effects compared to conventional therapies. In recent decades, significant studies have been conducted on the use of medicinal plants in the treatment of viral diseases, and the results have shown that the compounds extracted from plants have a wide range of antiviral activity. The present study is an overview of the use of herbal medicines in the treatment of viral diseases, the mechanism of action, as well as the challenges that the scientific community faces in the detailed research on each of the plant compounds.
Aims
This study was designed to investigate the phytochemical profile and the cytotoxic activities of olive leaves eco-friendly extracts from Chemlali cultivar.
Materials and methods
The Phenolic composition of olive leaves extracts, the antioxidant activity and the cytotoxic effects against MCF-7 and HepG2 cells were determined.
Results
Olive leaves extracts showed relevant total polyphenols contents. Oleuropein was the major detected phenolic compound reaching a concentration of 16.9 mg/ml. The antioxidant potential of the studied extracts varied from 23.7 to 46.5 mM Trolox equivalents as revealed by DPPH and ABTS assays. Cytotoxicity experiments showed similar trends for both HepG2 and MCF-7 cells with the infusion extract being the most active.
Conclusions
This study denotes that olive leaves may have great potential as endless bioresource of valuable bioactive compounds which may have a wide application.
Health-promoting impacts of olives and olive oil have fueled the fast expansion of the corresponding agro-industrial activities throughout the world, the Mediterranean region in particular. In olive mills, large amounts of resources are consumed and great deals of solid and liquid residues are inevitably formed. The olive mill wastewater (OMW) is an important by-product of olive oil production from both environmental and valorization potential points of view. Due to its high organic load, increased biological-to-chemical oxygen demand, low biodegradability, and high levels of recalcitrant and phytotoxic substances, OMW is an environmentally problematic effluent. On the other hand, it is a rich source of phenolic compounds with promising biological properties. Consequently, both treatment and valorization of this wastewater have been the focus of research during the past two decades. In this chapter, we present an overview of the advances in process of olive oil production, where OMW is originated from. Then, by introducing the chemical composition of OMW, advances in treatment and valorization of OMW as well as potential applications of OMW biophenols are concisely explained.
Background:
Drug resistance poses a challenge to malaria control measures. This calls for discovery & development of new chemotherapeutic agents. This study therefore was initiated to investigate the antimalarial activity of Olea europaea against Plasmodium berghei infected mice and to further ascertain in which fraction (s) the constituents responsible for anti-malarial activity are concentrated.
Methods:
The leaves of Olea europaea were extracted by maceration using 80% methanol and the crude extract was then successively fractionated with solvents of differing polarity (chloroform, n-butanol and water). The anti-malarial activity of various doses of the extract and fractions (200, 400 and 600 mg/kg) was evaluated using chemo-suppressive, curative, and repository tests. Parameters, including parasitemia, rectal temperature, body weight, and packed cell volume were determined to establish the activity.
Results:
The acute oral toxicity test result revealed that the LD50 values of the extract and fractions were greater than 2000 mg/kg in mice. The crude extract significantly reduced parasitemia (p < 0.001) and prolonged survival time (p < 0.001), in a dose-dependent manner, in all tests, as compared to the negative control group. Higher parasitemia suppression (58%) was achieved with the larger dose (600 mg/kg) in the 4-day suppressive test, suggesting that the crude extract has largely a chemo-suppressive activity. Parasitemia was significantly reduced (p < 0.001) by all fractions in all doses used when compared to the negative controls, with the rank order of n-butanol (51%) > chloroform>aqueous (21%) fractions. Larger (600 mg/kg) and middle (400 mg/kg) doses of the crude extract as well as the fractions ameliorated all the other parameters in a consistent manner, with the crude being more active than the fractions. Preliminary phytochemical analysis revealed the presence of secondary metabolites that were differentially distributed in the fractions.
Conclusion:
The findings collectively indicate that the plant is endowed with antimalarial activity, the activity being more in the crude extract than the fractions, owing to the presence of secondary metabolites that act independently or in synergy. The varying degree of antimalarial activity in the fractions suggests that non-polar and medium polar principles could be responsible for the observed activity.
We evaluated whether olive leaves (OLs) are effective as feed additives and supplements for ruminants and the potential methane reduction effects during in vitro fermentation. Two Hanwoo cows (460 ± 20 kg) equipped with cannula were fed Timothy hay and corn-based feed 3% of the body weight at a ratio of 6:4 (8:30 a.m. and 5:00 p.m.). Ruminal fluid from the cows was collected and mixed before morning feeding. In vitro batch fermentation was monitored after 12 and 24 h of incubation at 39 °C, and OLs were used as supplements to achieve the concentration of 5% in the basal diet. At 12 h of fermentation, methane production decreased in the 5% OLs group compared to that in the control group, but not at 24 h. The proportion of cellulose-degrading bacteria, Fibrobacter succinogenes, Ruminococcus albus, and Ruminococcus flavefaciens, tended to increase in the 5% OLs group at 12 h. The amount of ammonia produced was the same as the polymerase chain reaction result for Prevotella ruminicola. At 12 h, the proportion of Prevotella ruminicola was significantly higher in the 5% OLs group. OLs may be used incorporated with protein byproducts or other methane-reducing agents in animal feed.
453 Summary The merits of chemometrics in categorizing different Egyptian olive chemovarieties based on their compositional integrity were implemented in this study. Fingerprints of 9 different olive leaves varieties cultivated in Egypt were established using reversed-phase high-performance thin-layer chromatography (RP-HPTLC) prior to and after post-chromatographic derivatization with natural product-polyethylene glycol (NP/PEG) reagent and image analysis using ImageJ ® software in order to build 2 separate data matrices. The chromatographic fingerprints were separately subjected to unsupervised pattern recognition multivariate analysis to build 2 separate models using principal component analysis (PCA) and hierarchical clustering analysis (HCA) algorithms to explore the distribution pattern of different chemovarieties. The second model which involved olive samples' fingerprints after post-chromato-graphic derivatization exhibited greater ability to reveal a broader spectrum of phytoconstituents with enhanced sensitivity. Densito-metric RP-HPTLC quantification of oleuropein marker was compared to image analysis approach using Sorbfil TLC Videodensi-tometer ® by newly developed and validated methods. Densitometry exhibited better performance characteristics than image analysis method and therefore was executed for determination of oleuropein concentration in the 9 Egyptian olive varieties. Oleuropein marker solely was found to be inadequate for standardization of olive leaves varieties. This study demonstrated a comprehensive approach for the rapid classification of different Egyptian olive varieties, which is crucial to warranting their chemical-consistency and, thereafter, effective consistency.
Aqueous extracts and acid hydrolysates from olive leaf, rich in various phenolic compounds, were prepared under different experimental conditions. Their inhibitive action on the corrosion of copper in 0.5 M NaCl solutions was studied by electrochemical impedance spectroscopy and voltammetry. High performance liquid chromatography showed that the extracts were rich in oleuropeine, hydroxytyrosol, and elenolic acid. The acid hydrolysis extracts obtained at high temperature mainly contained hydroxytyrosol and elenolic acid and led to the highest inhibition efficiency (95%). The polarization curves were modelled on a large potential range (e.g. from −500 mV to −100 mV/SCE) using electrochemical kinetic laws to obtain a maximum of reliable information. Elenolic acid and oleuropein acted as cathodic-type corrosion inhibitors.
Secoiridoids play a key role in determining health benefits related to a regular consumption of extra-virgin olive oil (EVOO), in which they are generated from precursors of the same class naturally occurring in drupes and leaves of the olive (Olea europaea L.) plant. Here, reversed-phase liquid chromatography coupled to electrospray ionization and Fourier-transform single/tandem mass spectrometry (RPLC-ESI-FTMS and MS/MS) was employed for a structural elucidation of those precursors. The presence of three isoforms in both matrices was assessed for oleuropein ([M-H]− ion with m/z 539.1770) and was emphasized, for the first time, also for ligstroside (m/z 523.1821) and for the demethylated counterparts of the two compounds (m/z 525.1614 and 509.1665, respectively). However, only the prevailing isoform included an exocyclic double bond between carbon atoms C8 and C9, typical of oleuropein and ligstroside; the remaining, less abundant, isoforms included a C=C bond between C8 and C10. The same structural difference was also observed between secoiridoids named elenolic acid glucoside and secoxyloganin (m/z 403.1246). This study strengthens the hypothesis that secoiridoids including a C8=C10 bond, recently recognized as relevant species in EVOO extracts, arise mainly from specific enzymatic/chemical transformations occurring on major oleuropein/ligstroside-like precursors during EVOO production, rather than from precursors having that structural feature.
The effects of the polyphenolic compounds from virgin olive oil: tyrosol, hydroxytyrosol and oleuropein on the non-enzymatic lipid peroxidation induced by ascorbate-Fe2+ of rat liver microsomes were examined. The inhibition of light emission (maximal induced chemiluminescence) by oleuropein was concentration dependent. Hydroxytyrosol showed a substantial degree of inhibition against ascorbate-Fe2+ induced lipid peroxidation in rat liver microsomes that was at least 6 times higher than that observed in the presence of oleuropein. Inhibition of lipid peroxidation by tyrosol was not observed. In rat liver microsomes incubated alone or in the presence of tyrosol, the fatty acid composition was profoundly modified when subjected to in vitro peroxidation mediated by ascorbate-Fe2+, with a considerable decrease of 18:2n6 and 20:4n6; however, changes in fatty acid composition were not observed when microsomes were incubated with hydroxytyrosol. When oleuropein was used at low concentration (5, 15 μM) a considerable decrease of 20:4n6 was observed, but 18:2n6 was not modified; at higher concentration (30, 60 μM) changes in fatty acid composition were not observed. There was a very good correlation between the presence of oxidized phospholipids and the changes in polyunsaturated fatty acids previously observed. Thus, hydroxytyrosol showed the highest protection again oxidized phospholipid formation. The presence of oleuropein at low concentration (5, 15 μM) does not prevent the formation of oxidized phospholipids (8.02 ± 1.22 and 1.22 ± 1.22) but concentration higher than 30 μM avoids completely the formation of this molecules whereas tyrosol at any concentration assayed was found to be ineffective and allows the formation not only of oxidized phospholipids but also of oxidized cholesterol.
The effects of the polyphenolic compounds from virgin olive oil: tyrosol, hydroxytyrosol and oleuropein on the non-enzymatic lipid peroxidation induced by ascorbate-Fe2+ of rat liver microsomes were examined. The inhibition of light emission (maximal induced chemiluminescence) by oleuropein was concentration dependent. Hydroxytyrosol showed a substantial degree of inhibition against ascorbate-Fe2+ induced lipid peroxidation in rat liver microsomes that was at least 6 times higher than that observed in the presence of oleuropein. Inhibition of lipid peroxidation by tyrosol was not observed. In rat liver microsomes incubated alone or in the presence of tyrosol, the fatty acid composition was profoundly modified when subjected to in vitro peroxidation mediated by ascorbate-Fe2+, with a considerable decrease of 18:2n6 and 20:4n6; however, changes in fatty acid composition were not observed when microsomes were incubated with hydroxytyrosol. When oleuropein was used at low concentration (5, 15 M) a considerable decrease of 20:4n6 was observed, but 18:2n6 was not modified; at higher concentration (30, 60 M) changes in fatty acid composition were not observed. There was a very good correlation between the presence of oxidized phospholipids and the changes in polyunsaturated fatty acids previously observed. Thus, hydroxytyrosol showed the highest protection again oxidized phospholipid formation. The presence of oleuropein at low concentration (5, 15 M) does not prevent the formation of oxidized phospholipids (8.02 1.22 and 1.22 1.22) but concentration higher than 30 M avoids completely the formation of this molecules whereas tyrosol at any concentration assayed was found to be ineffective and allows the formation not only of oxidized phospholipids but also of oxidized cholesterol.
Olive oil is the principal source of fat in the Mediterranean diet, which has been associated with a lower incidence of coronary
heart disease and certain cancers. Olive oil is characterized by a high proportion of monounsaturated oleic acid, but the
main peculiarity of extra-virgin oil is the presence of remarkable quantities of phenolic compounds, notably hydroxytyrosol
and oleuropein, that provide high stability and strong taste. Recently, several studies have demonstrated that olive oil phenolics
are powerful antioxidants, both in vitro and in vivo, and exert additional potent biologic activities that could partially
account for the observed cardioprotective effects of the Mediterranean diet.
Both 2',3'-dideoxyadenosine and 2',3'-dideoxyinosine have been shown (Mitsuya, H., and Broder, S. (1987) Nature 325, 773-778) to have in vitro activity against the human immunodeficiency virus-1 (HIV). However, these dideoxynucleosides may be catabolized by human T cells, even when adenosine deaminase is inhibited by deoxycoformycin. To overcome this problem, we have synthesized the 2-fluoro-, 2-chloro-, and 2-bromo-derivatives of 2',3'-dideoxyadenosine. The metabolism and anti-HIV activity of the 2-halo-2',3'-dideoxyadenosine derivatives and of 2',3'-dideoxyadenosine were compared. The 2-halo-2',3'-dideoxyadenosine derivatives were not deaminated significantly by cultured CEM T lymphoblasts. Experiments with 2-chloro-2',3'-dideoxyadenosine showed that the T cells converted the dideoxynucleoside to the 5'-monophosphate, 5'-diphosphate, and 5'-triphosphate metabolites. At concentrations lower than those producing cytotoxicity in uninfected cells (3-10 microM), the 2-halo-2',3-dideoxyadenosine derivatives inhibited the cytopathic effects of HIV toward MT-2 T lymphoblasts, and retarded viral replication in CEM T lymphoblasts. Experiments with a deoxycytidine kinase-deficient mutant CEM T cell line showed that this enzyme was necessary for the phosphorylation and anti-HIV activity of the 2-chloro-2',3'-dideoxyadenosine. In contrast, 2',3'-dideoxyadenosine was phosphorylated by the deoxycytidine kinase-deficient mutant and retained anti-HIV activity in this cell line. Thus, the 2-halo derivatives of 2',3'-dideoxyadenosine, in contrast to 2',3'-dideoxyadenosine itself, are not catabolized by T cells. Their anti-HIV and anti-proliferative activities are manifest only in cells expressing deoxycytidine kinase. The in vivo implications of these results for anti-HIV chemotherapy are discussed.
Oleuropein, the bitter glucoside in green olives, and products of its hydrolysis were tested for antibacterial action against certain species of lactic acid bacteria involved in the brine fermentation of olives. Oleuropein was not inhibitory, but two of its hydrolysis products, the aglycone and elenolic acid, inhibited growth of the four species of lactic acid bacteria tested. Another hydrolysis product, beta-3,4-dihydroxyphenylethyl alcohol, was not inhibitory. The aglycone of oleuropein and elenolic acid were much more inhibitory when the broth medium contained 5% NaCl; 150 mug of either compound per ml prevented growth of Lactobacillus plantarum. A crude extract of oleuropein, tested by paper disk bioassay, was inhibitory to 3 of 17 species of bacteria screened, none of which were lactic acid bacteria. The acid hydrolysate of the extract was inhibitory to 11 of the bacteria, which included four species of lactic acid bacteria and other gram-positive and gram-negative species. Neither crude preparation was inhibitory to growth of the seven species of yeasts tested. A possible explanation is given for the previously reported observation that heating (3 min, 74 C) olives prior to brining renders them more fermentable by lactic acid bacteria. Results of a brining experiment indicated that oleuropein is degraded to antibacterial compounds when unheated olives are brined.
GAP31 (gelonium anti-HIV protein of 31 kDa) is an anti-HIV protein which we have identified and purified from a medicinal plant, Gelonium multiflorum. It is capable of inhibiting HIV-1 infection and replication. GAP31 also exhibits DNA topoisomerase inhibitor activity and RNA N-glycosidase activity. The ability of GAP31 to interrupt both DNA and RNA functions may be related to its multiple antiviral actions. To define the roles of these activities in the anti-HIV action of GAP31, a series of peptides corresponding to the N-terminal segment of GAP31 were synthesized and assayed for the aforementioned activities of the parent molecule. A 33-aa segment (KGATYITYVNFLNELRVKTKPEGNSHGIPSLRK) designated as K10-K42 is the shortest peptide necessary and sufficient for HIV-1 inhibition, DNA and RNA binding, and ribosome inactivation. The peptides were 2-5 orders of magnitude less active than GAP31. Truncation of 19 aa from the C terminus of K10-K42 resulted in the loss of all of these activities. On the other hand, deletion of N-terminal residues to give E23-K42 did not alter ribosome-inactivation activity but eliminated the other activities. These findings permit identification of a 7-aa sequence, KGATYIT, at the N terminus of K10-K42 that is critical for DNA binding and RNA binding, whereas a 9-aa sequence, SHGIPSLRK, at the C terminus is important to ribosome inactivation. Both regions contribute to anti-HIV activity. Histidine at position 35 is critical for all of these activities. The disparity of sequence requirements for inhibition of HIV infection and replication and for ribosome-inactivation activity suggests that the anti-HIV activity of most ribosome-inactivating proteins may not be the result of N-glycosidase activity alone. Mapping the minimal domain of GAP31 offers insights into the rational design of molecular mimetics of anti-HIV drugs.
The hedgehog (Hh) signaling pathway is involved in the development of many tissues. Here we show that sonic hedgehog (Shh) is involved in thymocyte development. Our data suggest that termination of Hh signaling is necessary for differentiation from CD4-CD8-double-negative (DN) to CD4+CD8+ double-positive (DP) thymocyte. Shh is produced by the thymic stroma, and Patched and Smoothened (Smo), the transmembrane receptors for Shh, are expressed in DN thymocytes. A neutralizing monoclonal antibody against Shh increases differentiation of DN to DP thymocytes, and Shh protein arrests thymocyte differentiation at the CD25+ DN stage, after T cell receptor beta (TCRbeta) gene rearrangement. We show that one consequence of pre-TCR signaling is downregulation of Smo, allowing DN thymocytes to proliferate and differentiate.
Interest in the health-promoting effects of virgin olive oil, an important part of the "Mediterranean diet", prompted us to determine the antiinflammatory effects of erythrodiol, beta-sitosterol and squalene, identified as major components of the so-called "unsaponifiable fraction" of virgin olive oil, as well as of the phenolic compounds from the "polar fraction": oleuropein, tyrosol, hydroxytyrosol and caffeic acid. Their activities were compared to those of both, total unsaponifiable and polar fractions. This study was designed to analyse the antiinflammatory effect of these specific compounds from virgin olive oil on edema in mice induced by either arachidonic acid (AA) or 12-O-tetradecanoylphorbol acetate (TPA). The inhibition of the myeloperoxidase (MPO), marker enzyme of the accumulation of neutrophils in the inflamed tissue, was also investigated by the TPA model. The topical application of the olive oil compounds (0.5 mg/ear) produced a variable degree of antiinflammatory effect with both assays. In the auricular edema induced by TPA, beta-sitosterol and erythrodiol from the unsaponifiable fraction of the oil showed a potent antiedematous effect with a 61.4% and 82.1% of inhibition respectively, values not very different to that of the reference indomethacin (85.6%) at 0.5 mg/ear. The four phenolics exerted a similar range of inhibition (33-45%). All compounds strongly inhibited the enzyme myeloperoxidase, indicating a reduction of the neutrophil influx in the inflamed tissues. The strongest inhibitor of AA edema was the total unsaponifiable fraction which inhibition was 34%, similar to that obtained by the reference drug dexamethasone at 0.05 mg/ear. Among the phenolics, oleuropein also produced an inhibition of about 30% with the same dose, but all the other components were found less active in this assay. The anti-inflammatory effects exerted by both unsaponifiable and polar compounds might contribute to the potential biological properties reported for virgin olive oil against different pathological processes.
Sonic hedgehog (Shh) is important in the growth and differentiation of a variety of cell types, including the development of T cells in the thymus. This prompted us to investigate whether Shh signaling is a functional component of the physiological response of human mature CD4(+) T cells following Ag recognition. In this study, we demonstrate that Shh and its receptor Patched (Ptc) are expressed on resting and activated human peripheral CD4(+) T cells. In approximately one-half of the randomly selected, anonymous blood donors tested, exposure of anti-CD3/28 Ab-activated CD4(+) T cells to the biologically active N-terminal Shh peptide increased the transcription of ptc, thereby demonstrating that Shh signaling had occurred. Furthermore, the addition of exogenous Shh amplified the production of IL-2, IFN-gamma, and IL-10 by activated CD4(+) T cells. The synthesis of IL-2 and IFN-gamma, but not IL-10, by CD4(+) T cells was down-regulated by the addition of neutralizing anti-Shh Ab. Cell surface expression of CD25 and CD69 on activated T cells was up-regulated by exogenous Shh, whereas in the presence of the neutralizing anti-Shh Ab expression it was reduced. Collectively, our findings demonstrate that Shh-mediated signaling is a physiological component of T cell responses, which acts to modulate CD4(+) T cell effector function.
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.
A new inhibitor of human immunodeficiency virus (HIV) has been isolated and purified to homogeneity from the seeds and fruits of the Momordica charantia. This compound, MAP 30 (Momordica Anti-HIV Protein), is a basic protein of about 30 kDa. It exhibits dose-dependent inhibition of cell-free HIV-1 infection and replication as measured by: (i) quantitative focal syncytium formation on CEM-ss monolayers; (II) viral core protein p24 expression; and (iii) viral-associated reverse transcriptase (RT) activity in HIV-1 infected H9 cells. The doses required for 50% inhibition (ID50) in these assays were 0.83, 0.22 and 0.33 nM, respectively. No cytotoxic or cytostatic effects were found under the assay conditions. These data suggest that MAP 30 may be a useful therapeutic agent in the treatment of HIV-1 infections. The sequence of the N-terminal 44 amino acids of MAP 30 has been determined.
The anti-HIV agent MAP30 (Momordica anti-HIV protein, 30 kDa) inhibits the proliferation of BC-2, an AIDS-related primary effusion lymphoma (PEL) cell line derived from an AIDS patient. BC-2 cells are latently infected with Kaposi's sarcoma-associated herpes virus (KSHV), also known as human herpes virus 8 (HHV8). We examined the effect of MAP30 on the expression of viral and cellular genes in BC-2 during latent and lytic states of the viral life cycle. By Northern analysis and RT-PCR, we found that MAP30 downregulates the expression of viral cyclin D (vCD), viral interleukin-6 (vIL-6), and viral FLIP (vFLIP), genes involved in cell cycle regulation, viral pathogenesis, and apoptosis. By pathway-specific cDNA microarray analysis, we found that BC-2 cells express high levels of egr-1, ATF-2, hsp27, hsp90, IκB, mdm2, skp1, and IL-2, cellular genes involved in mitogenesis, tumorigenesis, and inhibition of apoptosis in NFκB and p53 signaling pathways. These results define for the first time the specific cellular pathways involved in AIDS-related tumorigenesis and suggest specific novel targets for the treatment. Furthermore, we found that MAP30 downregulates the expression of egr-1, ATF-2, hsp27, hsp90, IκB, mdm2, and Skp1, while it upregulates the pro-apoptotic-related genes Bax, CRADD, and caspase-3. Thus, MAP30 modulates the expression of both viral and cellular genes involved in KS pathogenesis. These results provide valuable insight into the molecular mechanisms of MAP30 anti-KS action and suggest its utility as a therapeutic agent against AIDS-related tumors.
The Mediterranean diet, rich in fruit, vegetables, grain, and vegetable oil (mainly olive oil) is correlated with a lower incidence of coronary heart disease (CHD). Natural antioxidants contained in the Mediterranean diet might also play a role in the prevention of cardiovascular diseases, through inhibition of LDL oxidation. We tested this hypothesis “in vitro” by inducing LDL oxidation with copper sulphate and preincubating the samples with oleuropein, the bitter principle of olive, that is one of the major components of the polyphenolic fraction of olive oil. Oleuropein 10−5 M effectively inhibited CuSO4-induced LDL oxidation, as assessed by various parameters. We demonstrate in this investigation that polyphenolic components of the Mediterranean diet interfere with biochemical events that are implicated in atherogenetic disease, thus proposing a new link between the Mediterranean diet and prevention of CHD.
This study was designed to investigate the in vitro effects of phenolic compounds extracted from olive oil and from olive derived fractions. More specifically, we investigated the effects on platelets of 2-(3,4-di-hydroxyphenyl)-ethanol (DHPE), a phenol component of extra-virgin olive oil with potent antioxidant properties. The following variables were studied: aggregation of platelet rich plasma (PRP) induced by ADP or collagen, and thromboxane B2 production by collagen or thrombin-stimulated PRP. In addition, thromboxane B2 and 12-hydroxyeicosatetraenoic acid (12-HETE) produced during blood clotting were measured in serum. Preincubation of PRP with DHPE for at least 10 min resulted in maximal inhibition of the various measured variables. The IC50s (concentration resulting in 50% inhibition) of DHPE for ADP- or collagen-induced PRP aggregations were 23 and 67 μM, respectively. At 400 μM DHPE, a concentration which completely inhibited collagen-induced PRP aggregation, TxB2 production by collagen- or thrombin-stimulated PRP was inhibited by over 80 percent. At the same DHPE concentration, the accumulation of TxB2 and 12-HETE in serum was reduced by over 90 and 50 percent, respectively. We also tested the effects on PRP aggregation of oleuropein, another typical olive oil phenol, and of selected flavonoids (luteolin, apigenin, quercetin) and found them to be much less active. On the other hand a partially characterized phenol-enriched extract obtained from aqueous waste from olive oil showed rather potent activities. Our results are the first evidence that components of the phenolic fraction of olive oil can inhibit platelet function and eicosanoid formation in vitro, and that other, partially characterized, olive derivatives share these biological activities.
Oleuropein, the bitter glucoside of olives, and its hydrolysis products can possess antibacterial action. However, there is no information on the possible utilization of this polyphenolic compound; therefore studies have been made to assess its utilization as a major source of carbon. Various microorganisms associated with fermentation of olives (both desirable lactic acid bacteria and spoilage organisms) did use oleuropein, many without a significant delay in growth resulting in the appearance of a strong visible turbidity. Although the increase in oleuropein from 0.2 to 0.4% (w/v) had little or no effect on the spoilage organisms, the additional glucoside caused a delay in development of growth with some of the lactic acid bacteria. However, all of the latter cultures tested eventually grew and developed strong visible turbidity.
The human T-cell lines MT-2 and MT-4 carry the human T-cell leukemia virus type I (HTLV-I). When MT-2 and MT-4 were infected with HTLV-III, the probable etiologic agent of the acquired immune deficiency syndrome (AIDS), rapid cytopathogenic effects and cytotoxicity were observed that made it possible to titrate the biologically active virus in a plaque-forming assay. The cytopathogenic effects were preceded by the rapid induction and increase of HTLV-III antigens as revealed by immunofluorescence and immunoprecipitation. Activities of HTLV-III were neutralized by the human antibodies against the virus when immunofluorescence and plaque assays were used. Essentially the same results were obtained with the lymphadenopathy-associated virus (LAV1).
The development of a cytomorphologic infectivity microbioassay for human immunodeficiency virus (HIV) allows rapid, sensitive, and specific characterization of neutralizing antibodies or antiviral agents.
. Treatment of green olives for 2 min with dilute hot alkali before brining increased the release of sugars, B complex vitamins, amino acids and phenolic compounds, and enhanced the establishment of lactic acid bacteria in the brine. Two components of the ethyl acetate extract of green olives, which showed an antibacterial activity, were isolated and identified as the glycoside oleuropein and its phenolic aglycone. The inhibition of Lactobacillus plantarum by the ethyl acetate extract or by oleuropein was augmented by reducing the concentration of organic nitrogenous compounds, increasing the NaCl concentration in the assay medium and decreasing the inoculum size. Besides its activity towards various bacteria, oleuropein inhibited the growth of Geotrichum candidum Link, Rhizopus sp. and Rhizoctonia solani Kühn. On the basis of these findings, an explanation for some problems in the lactic fermentation of green olives is suggested.
A cell system was developed for the reproducible detection of human T-lymphotropic retroviruses (HTLV family) from patients with the acquired immunodeficiency syndrome (AIDS) or with signs or symptoms that frequently precede AIDS (pre-AIDS). The cells are specific clones from a permissive human neoplastic T-cell line. Some of the clones permanently grow and continuously produce large amounts of virus after infection with cytopathic (HTLV-III) variants of these viruses. One cytopathic effect of HTLV-III in this system is the arrangement of multiple nuclei in a characteristic ring formation in giant cells of the infected T-cell population. These structures can be used as an indicator to detect HTLV-III in clinical specimens. This system opens the way to the routine detection of HTLV-III and related cytopathic variants of HTLV in patients with AIDS or pre-AIDS and in healthy carriers, and it provides large amounts of virus for detailed molecular and immunological analyses.
The importance of ornithine decarboxylase (ODC) to cell proliferation is underscored by the complex array of cell-specific
mechanisms invoked to regulate its synthesis and activity. Misregulation of ODC has severe negative consequences on normal
cell function, including the acquisition of tumorigenic growth properties by cells overexpressing ODC. We hypothesize that
ODC gene expression is a candidate target for the anti-proliferative function of certain tumor suppressors. Here we show that
the Wilms' tumor suppressor WT1 binds to multiple sites within the human ODC promoter, as determined by DNase I protection
and methylation interference assays. The expression of WT1 in transfected HCT 116, NIH/3T3 and HepG2 cells represses activity
of the ODC promoter controlling expression of a luciferase reporter gene. In contrast, WT1 expression enhances ODC promoter
activity in SV40-transfected HepG2 cells. Both the extent of modulation of ODC gene expression and the mediating WT1 binding
elements are cell specific. Constructs expressing WT1 deletion mutants implicate two regions required for repressor function,
as well as an intrinsic activation domain. Understanding the regulation of ODC gene expression by WT1 may provide valuable
insights into the roles of both WT1 and ODC in development and tumorigenesis.
This study sought to update national estimates of the use of alternative therapies, to improve the quality of those estimates, and to examine differences between users and nonusers of alternative medicine. Data were analyzed from the general probability sample (N = 3450) of the 1994 Robert Wood Johnson Foundation National Access to Care Survey. The results indicate that nearly 10% of the U.S. population, almost 25 million persons, saw a professional in 1994 for at least one of the following four therapies: chiropractic, relaxation techniques, therapeutic massage, or acupuncture. Even though users of alternative therapies made almost twice as many visits to conventional (or orthodox) medical providers as nonusers made, the former still reported much higher levels of unmet need for medical care. The growing emphasis on market-driven health care and consumer choice suggests that alternative therapies could have a larger role in the health-care system of the future.
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.
The Hedgehog (Hh) family of secreted proteins is involved in a number of developmental processes as well as in cancer. Genetic and biochemical data suggest that the Sonic hedgehog (Shh) receptor is composed of at least two proteins: the tumor suppressor protein Patched (Ptc) and the seven-transmembrane protein Smoothened (Smo).
Using a biochemical assay for activation of the transcription factor Gli, a downstream component of the Hh pathway, we show here that Smo functions as the signaling component of the Shh receptor, and that this activity can be blocked by Ptc. The inhibition of Smo by Ptc can be relieved by the addition of Shh. Furthermore, oncogenic forms of Smo are insensitive to Ptc repression in this assay. Mapping of the Smo domains required for binding to Ptc and for signaling revealed that the Smo-Ptc interaction involves mainly the amino terminus of Smo, and that the third intracellular loop and the seventh transmembrane domain are required for signaling.
These data demonstrate that Smo is the signaling component of a multicomponent Hh receptor complex and that Ptc is a ligand-regulated inhibitor of Smo. Different domains of Smo are involved in Ptc binding and activation of a Gli reporter construct. The latter requires the third intracellular loop and the seventh transmembrane domain of Smo, regions often involved in coupling to G proteins. No changes in the levels of cyclic AMP or calcium associated with such pathways could be detected following receptor activation, however.
Substantial evidence suggests that oxidative modifications of low density lipoproteins (LDL) critically contribute to the pathogenesis and progression of human atherosclerosis. Oxidized LDL (oxLDL) are present in atherosclerotic plaques and contain oxysterols that exhibit a variety of adverse biological activities. Antioxidants have also been shown to prevent LDL modification. We have therefore assessed the efficacy of virgin olive oil phenolic compounds in preventing oxidative modifications of human LDL oxidized by UV light.
Cholesterol oxides formed during LDL photo-oxidation were determined by UV-HPLC in the presence of different concentrations of phenolic compounds and their pure components (tyrosol and oleuropein), and probucol, a widely used synthetic antioxidant. Electrophoretic mobility was also assayed. The results demonstrate that phenolic compounds are much more potent in preventing cholesterol oxide formation and apoproteic moiety modification than their pure components and probucol.
The beneficial effects of a Mediterranean diet may be ascribable not only to the high unsaturated/saturated fatty acid ratio characteristic of olive oil, but also to the unique antioxidant properties of its phenolic compounds.
Olive oil contains several phenolic compounds with antioxidant activity, whose levels depend strongly on the kind of cultivar grown, fruit ripening effects and the oil extraction process. Therefore, the beneficial effects exerted by olive oil consumption on the resistance of low density lipoproteins (LDLs) to oxidation depend not only on an increased intake of mono-unsaturated fatty acids (e.g. oleate) which are less prone to oxidation, but also phenolic antioxidants. The aim of this study was to analyze in vitro effects exerted on the oxidative modification of Cu-stimulated human LDL by two olive oil biophenols, i.e. 3,4-dihydroxyphenylethanol-elenolic acid (3,4-DHPEA-EA) and protocatecuic acid. These compounds have not been investigated in as much detail as the better-known olive oil biophenols - such as tyrosol (p-HPEA), o-coumaric acid, vanillic acid, caffeic acid, oleuropein and 3,4-dihydroxyphenylethanol (3,4-DHPEA). Modification of LDL was tested by measuring the formation of intermediate and end products of lipid peroxidation such as conjugated dienes, lipid hydroperoxides, cholesterol and cholesteryl ester oxides, as well as studying the decrease in oxidizable substrates like polyunsaturated fatty acids. In addition, the increase in LDL negative charges was evaluated. The results demonstrate the two-tested olive oil biophenols show high antioxidant activities. In particular, protocatecuic acid and 3,4-DHPEA-EA show an antioxidant activity comparable with that of caffeic acid, oleuropein and 3,4-DHPEA. They are not only able to retard lipid peroxidation, but also to reduce the extent of its activity.
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.
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%).
Olive oil is the principal source of fats in the Mediterranean diet, which has been associated with a lower incidence of coronary heart disease and certain cancers. Phenolic compounds, e.g., hydroxytyrosol and oleuropein, in extra-virgin olive oil are responsible for its peculiar pungent taste and for its high stability. Recent findings demonstrate that olive oil phenolics are powerful antioxidants, both in vitro and in vivo, and possess other potent biological activities that could partially account for the observed healthful effects of the Mediterranean diet.
Animal and in vitro studies suggest that olive oil phenols are effective antioxidants. The most abundant phenols in olive oil are the nonpolar oleuropein- and ligstroside-aglycones and the polar hydroxytyrosol and tyrosol. The aim of this study was to gain more insight into the metabolism of those phenols in humans. We measured their absorption in eight healthy ileostomy subjects. We also measured urinary excretion in the ileostomy subjects and in 12 volunteers with a colon. Subjects consumed three different supplements containing 100 mg of olive oil phenols on separate days in random order. Ileostomy subjects consumed a supplement with mainly nonpolar phenols, one with mainly polar phenols and one with the parent compound oleuropein-glycoside. Subjects with a colon consumed a supplement without phenols (placebo) instead of the supplement with oleuropein-glycoside. Ileostomy effluent and urine were collected for 24 h after supplement intake. Tyrosol and hydroxytyrosol concentrations were low (< 4 mol/100 mol of intake) in the ileostomy effluent, and no aglycones were detected. We estimated that the apparent absorption of phenols was at least 55-66% of the ingested dose. Absorption was confirmed by the excretion of tyrosol and hydroxytyrosol in urine. In ileostomy subjects, 12 mol/100 mol and in subjects with a colon, 6 mol/100 mol of the phenols from the nonpolar supplement were recovered in urine as tyrosol or hydroxytyrosol. In both subject groups, 5--6 mol/100 mol of the phenols was recovered from the polar supplement. When ileostomy subjects were given oleuropein-glycoside, 16 mol/100 mol was recovered in 24-h urine, mainly in the form of hydroxytyrosol. Thus, humans absorb a large part of ingested olive oil phenols and absorbed olive oil phenols are extensively modified in the body.
In the Mediterranean basin, olive oil, along with fruits, vegetables, and fish, is an important constituent of the diet, and is considered a major factor in preserving a healthy and relatively disease-free population. Epidemiological data show that the Mediterranean diet has significant protective effects against cancer and coronary heart disease. We present evidence that it is the unique profile of the phenolic fraction, along with high intakes of squalene and the monounsaturated fatty acid, oleic acid, which confer its health-promoting properties. The major phenolic compounds identified and quantified in olive oil belong to three different classes: simple phenols (hydroxytyrosol, tyrosol); secoiridoids (oleuropein, the aglycone of ligstroside, and their respective decarboxylated dialdehyde derivatives); and the lignans [(+)-1-acetoxypinoresinol and pinoresinol]. All three classes have potent antioxidant properties. High consumption of extra-virgin olive oils, which are particularly rich in these phenolic antioxidants (as well as squalene and oleic acid), should afford considerable protection against cancer (colon, breast, skin), coronary heart disease, and ageing by inhibiting oxidative stress.
Typical components of the Mediterranean diet, such as olive oil and red wine, contain high concentrations of complex phenols, which have been suggested to have an important antioxidant role. The aim of the present work was to determine the inhibitory potency of compounds such as oleuropein, hydroxytyrosol, and other structurally related compounds, such as gallic acid, toward reactive oxygen species generation and free radical scavenging ability. The potency of these compounds was also examined with respect to protecting in vitro low-density lipoprotein oxidation. These studies indicate that complex phenols, such as hydroxytyrosol, and gallic acid both inhibit free radical generation and act as free radical scavengers. The use of three different approaches to determine antioxidant potency demonstrates that activity in one test does not necessarily correlate with activity in another. It was also demonstrated that the presence of two phenolic groups is not always associated with antioxidant activity.
Olive oil is the principal source of fat in the Mediterranean diet, which has been associated with a lower incidence of coronary heart disease and certain cancers. Extra-virgin olive oil contains a considerable amount of phenolic compounds, for example, hydroxytyrosol and oleuropein, that are responsible for its peculiar taste and for its high stability. Evidence is accumulating to demonstrate that olive oil phenolics are powerful antioxidants, both in vitro and in vivo; also, they exert other potent biological activities that could partially account for the observed healthful effects of the Mediterranean diet.
In the present work, virgin olive oil, sunflower oil and a vegetable shortening were used as cooking oils for the deep-frying and pan-frying of potatoes, for eight successive sessions, under the usual domestic practice. Several chemical and physicochemical parameters (acidic value, peroxide value, total polar artefacts, total phenol content and triglyceride fatty acyl moiety composition) were assayed during frying operations in order to evaluate the status of the frying oils, which were found within expected ranges similar to those previously reported. The oil fatty acids were effectively protected from oxidation by the natural antioxidants. The frying oil absorption by the potatoes was quantitated within 6.1-12.8%, depending on the oil type and the frying process. The retention of α- and (β + γ)-tocopherols during the eight fryings ranged from 85-90% (first frying) to 15-40% (eighth frying), except for the (β + γ)-tocopherols of sunflower oil, which almost disappeared after the sixth frying. The deterioration during the successive frying of several phenolic species present in virgin olive oil is reported for the first time. The retention of total phenolics ranged from 70-80% (first frying) to 20-30% (eighth frying). Tannic acid, oleuropein and hydroxytyrosol-elenolic acid dialdeydic form showed remarkable resistance in all frying sessions in both frying methods, while hydroxytyrosol and hydroxytyrosol-elenolic acid were the faster eliminated. The deterioration of the other phenolic species account for 40-50% and 20-30% for deep-frying and pan-frying, respectively, after three to four frying sessions, which are the most usual in the household kitchen. Deep-frying resulted in better recoveries of all the parameters examined. The correlation of the deterioration rate of the phenolic compounds and tocopherols during frying is discussed and the nutritional aspects of the natural antioxidant intake, through the oil absorbed by the potatoes, are evaluated.
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.
It has been postulated that the components in olive oil in the Mediterranean diet, a diet which is largely vegetarian in nature, can contribute to the lower incidence of coronary heart disease and prostate and colon cancers. The Mediterranean diet includes the consumption of large amounts of olive oil. Olive oil is a source of at least 30 phenolic compounds. The major phenolic compounds in olive oil are oleuropein, hydroxytyrosol and tyrosol. Recently there has been a surge in the number of publications that has investigated their biological properties. The phenolic compounds present in olive oil are strong antioxidants and radical scavengers. Olive "waste water" also possesses compounds which are strong antioxidant and radical scavengers. Typically, hydroxytyrosol is a superior antioxidant and radical scavenger to oleuropein and tyrosol. Hydroxytyrosol and oleuropein have antimicrobial activity against ATTC bacterial strains and clinical bacterial strains. Recent syntheses of labeled and unlabelled hydroxytyrosol coupled with superior analytical techniques have enabled its absorption and metabolism to be studied. It has recently been found that hydroxytyosol is renally excreted unchanged and as the following metabolites as its glucuronide conjugate, sulfate conjugate, homovanillic acid, homovanillic alcohol, 3,4-dihydroxyphenylacetic acid and 3,4-dihydroxyphenylacetaldehyde. Studies with tyrosol have shown that it is excreted unchanged and as its conjugates. This review summarizes the antioxidant abilities; the scavenging abilities and the biological fates of hydroxytyrosol, oleuropein and tyrosol which have been published in recent years.
Epidemiology suggests that Mediterranean diets are associated with reduced risk of cardiovascular disease. Because monocyte adhesion to the endothelium is crucial in early atherogenesis, we evaluated whether typical olive oil and red wine polyphenols affect endothelial-leukocyte adhesion molecule expression and monocyte adhesion.
Phytochemicals in olive oil and red wine, including oleuropein, hydroxytyrosol, tyrosol, elenolic acid, and resveratrol, with or without antioxidant activity, were incubated with human umbilical vein endothelial cells for 30 minutes, followed by co-incubation with bacterial lipopolysaccharide or cytokines to trigger adhesion molecule expression. At nutritionally relevant concentrations, only oleuropein, hydroxytyrosol, and resveratrol, possessing a marked antioxidant activity, reduced monocytoid cell adhesion to stimulated endothelium, as well as vascular cell adhesion molecule-1 (VCAM-1) mRNA and protein by Northern analysis and cell surface enzyme immunoassay. Reporter gene assays with deletional VCAM-1 promoter constructs indicated the relevance of nuclear factor-kappaB, activator protein-1, and possibly GATA binding sites in mediating VCAM-1 transcriptional inhibition. The involvement of nuclear factor-kappaB and activator protein-1 was finally demonstrated at electrophoretic mobility shift assays.
Olive oil and red wine antioxidant polyphenols at nutritionally relevant concentrations transcriptionally inhibit endothelial adhesion molecule expression, thus partially explaining atheroprotection from Mediterranean diets.
The Hedgehog (Hh) and Wnt family proteins, and the bone morphogenetic proteins (BMPs) 2 and 4, act as morphogens during vertebrate embryogenesis and organogenesis by regulating patterning and cell fate. They have recently been found to have a role in regulating cell fate and determination in self-renewing tissues in adults, such as the immune system and haematopoietic system. This Review presents studies on the role of Sonic Hh (Shh), Wnts and BMP2/4 in the regulation of thymocyte development. Shh and BMP2/4 act as negative regulators of thymocyte development. By contrast, Wnt signalling, through beta-catenin, has a positive role in the control of T-cell development, such that an absence or reduction in the Wnt signal leads to a reduction in cell number and cell proliferation rate and differentiation to the CD4+CD8+ double-positive stage.
Antimicrobial properties of oleuropein and products of its hydrolysis from green olives Comparative antibacterial and antifungal effects of some phenolic compounds
- H P Fleming
- W M Walter
- J L Jr
- Etchells
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Olive leaf extract. The new oral treatment to counteract most types of pathological organisms
- Walker
M. Walker, Olive leaf extract. The new oral treatment to counteract
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- P M Furneri
- A Marino
- A Saija
- N Uccella
- G Bisignano
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Inhibition of platelet aggregation and eicosanoid production by phenolic components of olive oil
- A Petroni
- M Blasevich
- M Salami
- N Papini
- G F Montedoro
- C Galli
A. Petroni, M. Blasevich, M. Salami, N. Papini, G.F. Montedoro,
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- S Lee-Huang
- P L Huang
- P L Nara
- H C Chen
- H F Kung
- P Huang
- H I Huang
S. Lee-Huang, P.L. Huang, P.L. Nara, H.C. Chen, H.F. Kung, P.
Huang, H.I. Huang, MAP 30: a new inhibitor of HIV-1 infection
and replication, FEBS Lett. 272 (1990) 12-18.
Utilization of oleuropein by microorganisms associated with olive fermentations
- A Garrido-Fernandez
- R H Vaughn
A. Garrido-Fernandez, R.H. Vaughn, Utilization of oleuropein
by microorganisms associated with olive fermentations, Can. J.
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Inhibition of platelet aggregation and eicosanoid production by phenolic components of olive oil
- Petroni