Effects of oleuropein on tumor cell growth and bone remodelling: Potential clinical implications for the prevention and treatment of malignant bone diseases.

Oleuropein (Ole) is the main bioactive phenolic compound present in olive leaves, fruits and olive oil. This molecule has been shown to exert beneficial effects on several human pathological conditions. In particular, recent preclinical and observational studies have provided evidence that Ole exhibits chemo-preventive effects on different types of human tumors. Studies undertaken to elucidate the specific mechanisms underlying these effects have shown that this molecule may thwart several key steps of malignant progression, including tumor cell proliferation, survival, angiogenesis, invasion and metastasis, by modulating the expression and activity of several growth factors, cytokines, adhesion molecules and enzymes involved in these processes. Interestingly, experimental observations have highlighted the fact that most of these signalling molecules also appear to be actively involved in the homing and growth of disseminating cancer cells in bones and, ultimately, in the development of metastatic bone diseases. These findings, and the experimental and clinical data reporting the preventive activity of Ole on various pathological conditions associated with a bone loss, are indicative of a potential therapeutic role of this molecule in the prevention and treatment of cancer-related bone diseases. This paper provides a current overview regarding the molecular mechanisms and the experimental findings underpinning a possible clinical role of Ole in the prevention and development of cancer-related bone diseases.

Content of phenolic compounds and mannitol in olive leaves extracts from six Spanish cultivars: Extraction with the Soxhlet method and pressurized liquids.

Olive leaves are considered a promising source of bioactives such as phenolic compounds and mannitol. The extraction of high added value products is an issue of great interest and importance from the point of view of their exploitation. However, the content of these compounds can differ between cultivars and extraction methods. In this work, six olive leaves cultivars, including three wild cultivars, and two extraction processes (an innovative and alternative technique, pressurized liquid extraction, and a conventional Soxhlet extraction) were evaluated and compared towards the selective recovery of bioactive compounds. The wild cultivars showed the highest content of phenolic and flavonoid compounds, being oleuropein the compound present in higher amount. Findings also revealed that the highest mannitol content in the extracts was observed with the commercial cultivars, specifically in Arbequina. It is thus possible to decide which cultivars to use in order to obtain the highest yield of each bioproduct.

Extraction of oleuropein and luteolin-7-O-glucoside from olive leaves: Optimization of technique and operating conditions.

Olive leaves have become a promising source of phenolic compounds and flavonoids with high added value. Phenolic compounds and flavonoids are important sources of antioxidants and bioactives, and one of the processes used to effectively produce them is extraction via solvents, using aqueous ethanol solutions. To obtain the highest extraction yield per kg of biomass, olive leaves were extracted using a conventional technique (dynamic maceration) and an emerging technology, such as pressurized liquid extraction. Studies of the factors that influence these processes were performed: temperature, leaf moisture content, solvent/solid, and aqueous ethanol concentration were optimized using the central composite and Box-Behnken experiment designs. Pressurized liquid extraction resulted in more efficient oleuropein and luteolin-7-O-glucoside extraction than dynamic maceration. The operational conditions for maximizing the recovery of phenolic compounds and flavonoids and antioxidant capacity were determined to be 190 °C, leaf moisture content of 5%, and aqueous ethanol concentration of 80%.

Structure-antioxidant activity relationship of ß-cyclodextrin inclusion complexes with olive tyrosol, hydroxytyrosol and oleuropein: Deep insights from X-ray analysis, DFT calculation and DPPH assay.

Olives and olive oil, a key food type of the Mediterranean diets, are packed with various important polyphenols including oleuropein (OLE), hydroxytyrosol (HTY) and tyrosol (TYR). OLE and HTY are highly powerful antioxidants and play a prime role in the therapeutics of free radical-related diseases. Their molecular stabilities and antioxidant properties can be improved by cyclodextrin (CD) encapsulation. Here, we present a systematic investigation on the inclusion complexes of ß-CD-TYR (1), ß-CD-HTY (2) and ß-CD-OLE (3) by combined single-crystal structure determination, DFT complete-geometry optimization and DPPH antioxidant assay. X-ray analysis and DFT calculation reveal the preference of inclusion geometry with deep protrusion of the aromatic ring moieties of TYR, HTY and OLE from the ß-CD O6-H-side, and the common host-guest stabilization scheme via intermolecular O-H⋯O hydrogen bonding interactions. No polyphenol OH group is shielded in the ß-CD cavity, in contrast to the structures of ß-CD-tea catechins complexes. The established host-guest O-H⋯O hydrogen bonds help to elevate antioxidant capacities of the olive polyphenols upon ß-CD encapsulation. The order of antioxidant activity 2 >3 ≫ 1 based on the DPPH measurement is in fair agreement with their relative thermodynamic stabilities derived from DFT calculation.

The protective role of plant biophenols in mechanisms of Alzheimer's disease.

Self-assembly of amyloid beta peptide (Aß) into the neurotoxic oligomers followed by fibrillar aggregates is a defining characteristic of Alzheimer's disease (AD). Several lines of proposed hypotheses have suggested the mechanism of AD pathology, though the exact pathophysiological mechanism is not yet elucidated. The poor understanding of AD and multitude of adverse responses reported from the current synthetic drugs are the leading cause of failure in the drug development to treat or halt the progression of AD and mandate the search for safer and more efficient alternatives. A number of natural compounds have shown the ability to prevent the formation of the toxic oligomers and disrupt the aggregates, thus attracted much attention. Referable to the abundancy and multitude of pharmacological activities of the plant active constituents, biophenols that distinguish them from the other phytochemicals as a natural weapon against the neurodegenerative disorders. This review provides a critical assessment of the current literature on in vitro and in vivo mechanistic activities of biophenols associated with the prevention and treatment of AD. We have contended the need for more comprehensive approaches to evaluate the anti-AD activity of biophenols at various pathologic levels and to assess the current evidences. Consequently, we highlighted the various problems and challenges confronting the AD research, and offer recommendations for future research.

The apoptotic and autophagic properties of two natural occurring prodrugs, hyperoside and hypoxoside, against pancreatic cancer cell lines.

Pancreatic cancer is only the 12th most common cancer, but the fourth leading cause of cancer-related deaths in the world. This is due to late prognosis, poor response to chemotherapy and early metastases. Natural prodrugs may play an important role in the treatment of pancreatic cancer. The main aim of this study was to determine the cytotoxicity of five natural prodrugs, namely harpagoside, hyperoside, hypoxoside, oleuropein and polydatin, by investigating apoptosis and autophagy as possible mechanism/s of action. Hypoxoside and hyperoside have shown selective cytotoxicity at IC50 values of ∼25 and 50µM against INS-1 and MIA PaCa-2 pancreatic cancer cells, respectively. Hypoxoside and hyperoside induced G2/M phase arrest and caspase-3 activation in INS-1 and MIA PaCa-2 cells, respectively. Hoechst/phalloidin staining confirmed morphological changes, including condensed chromatin multinucleation, membrane blebbing and loss of cytoskeletal arrangement in INS-1 and MIA PaCa-2 cells. Acridine orange staining was absent in INS-1 (hypoxoside) and MIA PaCa-2 (hyperoside) treated cells, whereas LC3B expression was not significantly increased. INS-1 and MIA PaCa-2 treated cells favour the cell death pathway, apoptosis, over the cell survival pathway, autophagy.

Olive mill wastewater microconstituents composition according to olive variety and extraction process.

Olive oil production yields a considerable amount of wastewater, a powerful pollutant that is currently discarded but could be considered as a potential source of valuable natural products due to its content in phenolic compounds and other natural antioxidants. The aim of this work was to explore the variability in olive mill wastewater composition from Algerian olive oil mills considering extraction processes (traditional discontinuous press vs 3-phases centrifugal system) and olive varieties (Azerraj, Sigoise, Chemlal). Whereas pH, dry or organic matter content didn't vary, there was a significant difference in ash content according to extraction process and olive variety. Carotenoid content was 2.2-fold higher with 3-phases than with press systems whereas tocopherol content was not significantly different. Among the phenolic compounds quantified, tyrosol was usually the most abundant whereas oleuropein concentrations were highly variable. Differences in phenolic compound concentrations were more pronounced between olive varieties than between processes.

On-field monitoring of fruit ripening evolution and quality parameters in olive mutants using a portable NIR-AOTF device.

This study optimizes the application of portable Near Infrared-Acousto Optically Tunable Filter (NIR) device to meet the increasing demand for cost-effective, non-invasive and easy-to-use methods for measuring physical and chemical properties during olive fruit development. Fruits from different phenotypically cultivars were sampled for firmness, total and specific phenols detection by HPLC, total anthocyanins, chlorophyll and carotenoids detection by spectrophotometry. On the same fruits, a portable NIR device in diffuse reflectance mode was employed for spectral detections. Predictive models for firmness, chlorophyll, anthocyanins, carotenoids and rutin were developed by Partial Least Square analysis. Oleuropein, verbascoside, 3,4-DHPEA-EDA, and total phenols were used to develop a validation model. Internal cross-validation was applied for calibration and predictive models. The standard errors for calibration, cross-validation, prediction, and RPD ratios (SD/SECV) were calculated as references for the model effectiveness. The determination of the optimal harvesting time facilitates the production of high quality extra virgin olive oil and table olives.

Fermentation of table olives by oleuropeinolytic starter culture in reduced salt brines and inactivation of Escherichia coli O157:H7 and Listeria monocytogenes.

The effect of an autochthonous starter culture developed by oleuropeinolytic strains belonging to the Lactobacillus plantarum group on the physicochemical and microbiological characteristics and the biophenol content of table olives fermented under reduced salt conditions was studied. Black (cv. Kalamata) and green (cv. Chalkidikis) olives were fermented in two different kinds of brine (Brine A containing 2.3% NaCl, 32.3mM Ca-acetate and 33.9mM Ca-lactate and Brine B containing 4% NaCl, pH5.0 in both brines). The sensory attributes of olives fermented by oleuropeinolytic starter culture assessed by a trained panel did not differ significantly compared with industrial processing. It is possible to carry out significant changes in table olive processing applying a completely microbiological procedure using oleuropeinolytic strains of the L. plantarum group as both the debittering and the fermentation agent in order to achieve improved sensorial and nutritional characteristics of the final product. Table olives processed by the suggested methodology may constitute a good source of biophenols in the diet, especially hydroxytyrosol and tyrosol. The inactivation potential of Escherichia coli O157 EDL-932 and Listeria monocytogenes Scott A in olives fermented by oleuropeinolytic starter culture was evaluated. The population of each pathogen in olive homogenates of both cultivars is inactivated by more than 6logCFU/ml in less than 24h. When whole fermented olives were submerged in peptone/saline (containing 6.7logCFU/ml of the relevant bacterial pathogen) for 30min followed by rinsing in distilled water, the population of viable foodborne pathogens dropped more than 4 logs in olive pulp. During subsequent storage at 22 or 4°C the population of L. monocytogenes Scott A was further eliminated under the detection limit in both olive cultivars whereas the population of E. coli O157 EDL-932 could be detected in olives stored in peptone/saline at 22°C for 7days. The inhibitory effect of olives fermented by oleuropeinolytic starter culture in reduced salt brines on pathogens is due to the antimicrobial activity of the phenolic compounds and the antagonistic action of the associated microflora.

Ethnobotanical survey of medicinal plants used in the Maseru district of Lesotho.

ETHNOPHARMACOLOGICAL RELEVANCE: Ethnobotanical knowledge in Lesotho is passed on orally from one generation to another. As a result it has not been well documented. Existing publications have relied on previous literature and are limited either in terms of scope or coverage. Furthermore, some of them are out of print. Therefore, there are gaps in the documentation of medicinal plants used in Lesotho. AIM OF THE STUDY: The purpose of the current study is to investigate common ailments in Lesotho's traditional medicine and document plants that are used in treating such ailments. MATERIALS AND METHODS: Interviews were conducted in five urban and four rural areas of the capital town of Maseru, by means of questionnaires to elicit information on medicinal plant use to cure common ailments. The informants were 20 males and seven females comprising 15 traditional healers, 11 herbalists and one pharmacist. RESULTS: Reproductive ailments were found to be the most commonly treated, followed by respiratory, degenerative and digestive problems. A list of the 80 plants used for treating the common ailments is given. A total of 44 families is represented, with Asteraceae, Fabaceae, Asphodelaceae and Poaceae families having the highest number of species used for medicinal purposes. The most frequently mentioned medicinal plants in interviews include; Elephantorrhiza elephantina, Pentanisia prunelloides, Hypoxis hermerocallidea, Eriocephalus sp., Salvia runcinata, Scabiosa columbaria, Dicoma anomala, Morella serrata, Xysmalobium undulatum, and Leobordea lanceolata. Due to the high demand of medicinal plants, some species such as L. lanceolata, Tephrosia capensis, E. elephantina, D. anomala and P. prunelloides were reported as over-harvested. In some cases animal products are added to the medicinal plants to enhance their curative abilities. CONCLUSIONS: A total of 80 plants were recorded in the study as treating 38 common ailments in the Maseru district of Lesotho. Records of eight medicinal plants and 146 new medicinal uses of 34 plants that were not recorded elsewhere in literature are reported in the current study for the first time. The new records of medicinal plants used in traditional healing practices in Lesotho clearly show the need to document these practices, and the wealth of new knowledge gained with the current study reinforces the importance of extending the study to other parts of Lesotho.

Characteristics of oleuropeinolytic strains of Lactobacillus plantarum group and influence on phenolic compounds in table olives elaborated under reduced salt conditions.

The technological characteristics of five oleuropeinolytic strains of the Lactobacillus plantarum group selected within 135 isolates from table olives were investigated. The metabolism of phenolic compounds during elaboration of green (cv. Chalkidikis) and black (cv. Kalamata) olives under reduced salt conditions was evaluated. Olives of both cultivars were fermented in two different kinds of brine (Brine A containing 2.3% NaCl, 32.3 mM Ca-acetate and 33.9 mM Ca-lactate and Brine B containing 4% NaCl, pH 5.0 in both brines) by five selected strains of L. plantarum group. After 60 days of fermentation, the analysis of phenolic compounds was performed by HPLC and nine compounds were identified and quantified: oleuropein, hydroxytyrosol, tyrosol and vanillin and the phenolic acids protocatechuic, caffeic, p-hydroxybenzoic, vanillic and p-coumaric acid. The study can lead to the development of starter culture potentially active in biological debittering of olives during fermentation in order to unify the debittering and fermentation process during elaboration of table olives.

Therapeutic approaches against common structural features of toxic oligomers shared by multiple amyloidogenic proteins.

Impaired proteostasis is one of the main features of all amyloid diseases, which are associated with the formation of insoluble aggregates from amyloidogenic proteins. The aggregation process can be caused by overproduction or poor clearance of these proteins. However, numerous reports suggest that amyloid oligomers are the most toxic species, rather than insoluble fibrillar material, in Alzheimer's, Parkinson's, and Prion diseases, among others. Although the exact protein that aggregates varies between amyloid disorders, they all share common structural features that can be used as therapeutic targets. In this review, we focus on therapeutic approaches against shared features of toxic oligomeric structures and future directions.