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Robert M. Williams - One of the best experts on this subject based on the ideXlab platform.
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Synthesis of (+/-)-Oleocanthal via a Tandem Intramolecular Michael Cyclization-HWE Olefination.
Tetrahedron Letters, 2009Co-Authors: Brandon J. English, Robert M. WilliamsAbstract:Abstract A synthesis of racemic Oleocanthal has been accomplished in 11 steps from 1,3 propanediol by a key tandem intramolecular Michael cyclization–Horner–Wadsworth–Emmons olefination.
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synthesis of Oleocanthal via a tandem intramolecular michael cyclization hwe olefination
Tetrahedron Letters, 2009Co-Authors: Brandon J. English, Robert M. WilliamsAbstract:Abstract A synthesis of racemic Oleocanthal has been accomplished in 11 steps from 1,3 propanediol by a key tandem intramolecular Michael cyclization–Horner–Wadsworth–Emmons olefination.
Khalid El A Sayed - One of the best experts on this subject based on the ideXlab platform.
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the olive oil phenolic Oleocanthal modulates estrogen receptor expression in luminal breast cancer in vitro and in vivo and synergizes with tamoxifen treatment
European Journal of Pharmacology, 2017Co-Authors: Nehad M. Ayoub, Hassan Y. Ebrahim, Mohamed M. Mohyeldin, Abu Bakar Siddique, Khalid El A SayedAbstract:Luminal breast cancer represents a therapeutic challenge in terms of aggressive disease and emerging resistance to targeted therapy. (-)-Oleocanthal has demonstrated anticancer activity in multiple human cancers. The goal of this study was to explore the effect of (-)-Oleocanthal treatment on growth of luminal breast cancer cells and to examine the effect of combination of (-)-Oleocanthal with tamoxifen. Results showed that (-)-Oleocanthal inhibited growth of BT-474, MCF-7, and T-47D human breast cancer cells in mitogen-free media with IC50 values of 32.7, 24.07, and 80.93µM, respectively. Similarly, (-)-Oleocanthal suppressed growth of BT-474, MCF-7, and T-47D cells in 17β-estradiol-supplemented media with IC50 values of 22.28, 20.77, and 83.91µM, respectively. Combined (-)-Oleocanthal and tamoxifen treatments resulted in a synergistic growth inhibition of BT-474, MCF-7, and T-47D cells with combination index values of 0.65, 0.61, and 0.53 for each cell line, respectively. In-silico docking studies indicated high degree of overlapping for the binding of (-)-Oleocanthal and 17β-estradiol to estrogen receptors, while (-)-Oleocanthal and tamoxifen have distinguished binding modes. Treatment with 5mg/kg or 10mg/kg (-)-Oleocanthal resulted in 97% inhibition of tumor growth in orthotopic athymic mice bearing BT-474 tumor xenografts compared to vehicle-treated animals. (-)-Oleocanthal treatment reduced total levels of estrogen receptors in BT-474 cells both in vitro and in vivo. Collectively, (-)-Oleocanthal showed a potential beneficial effect in suppressing growth of hormone-dependent breast cancer and improving sensitivity to tamoxifen treatment. These findings provide rational for evaluating the effect of (-)-Oleocanthal in combination with endocrine treatments in luminal breast cancer.
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Oleocanthal Enhances Amyloid‑β Clearance from the Brains of TgSwDI Mice and in Vitro across a Human Blood-Brain Barrier Model
2016Co-Authors: Hisham Qosa, Khalid El A Sayed, Mohamed M. Mohyeldin, Yazan S. Batarseh, Jeffrey N. Keller, Amal KaddoumiAbstract:ABSTRACT: Numerous clinical and preclinical studies have suggested several health promoting effects for the dietary consumption of extra-virgin olive oil (EVOO) that could protect and decrease the risk of developing Alzheimer’s disease (AD). Moreover, recent studies have linked this protective effect to Oleocanthal, a phenolic secoiridoid component of EVOO. This protective effect of Oleocanthal against AD has been related to its ability to prevent amyloid-β (Aβ) and tau aggregation in vitro, and enhance Aβ clearance from the brains of wild type mice in vivo; however, its effect in a mouse model of AD is not known. In the current study, we investigated the effect of Oleocanthal on pathological hallmarks of AD in TgSwDI, an animal model of AD. Mice treatment for 4 weeks with Oleocanthal significantly decreased amyloid load in the hippocampal parenchyma and microvessels. This reduction was associated with enhanced cerebral clearance of Aβ across the blood-brain barrier (BBB). Further mechanistic studies demonstrated Oleocanthal to increase the expression of important amyloid clearance proteins at the BBB including P-glycoprotein and LRP1, and to activate the ApoE-dependent amyloid clearance pathway in the mice brains. The anti-inflammatory effect of Oleocanthal in the brains of these mice was also obvious where it was able to reduce astrocytes activation and IL-1β levels. Finally, we could recapitulate the observed protective effect of Oleocanthal in an in vitro human-based model, which could argue against species difference in response to Oleocanthal. In conclusion, findings from in vivo and in vitro studies provide further support for the protective effect of Oleocanthal against the progression of AD
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olive oil derived Oleocanthal as potent inhibitor of mammalian target of rapamycin biological evaluation and molecular modeling studies
Phytotherapy Research, 2015Co-Authors: Mohammad A. Khanfar, Sanaa K. Bardaweel, Mohamed R. Akl, Khalid El A SayedAbstract:The established anticancer and neuroprotective properties of Oleocanthal combined with the reported role of mammalian target of rapamycin (mTOR) in cancer and Alzheimer's disease development encouraged us to examine the possibility that Oleocanthal inhibits mTOR. To validate this hypothesis, we docked Oleocanthal into the adenosine triphosphate binding pocket of a close mTOR protein homologue, namely, PI3K-γ. Apparently, Oleocanthal shared nine out of ten critical binding interactions with a potent dual PIK3-γ/mTOR natural inhibitor. Subsequent experimental validation indicated that Oleocanthal indeed inhibited the enzymatic activity of mTOR with an IC50 value of 708 nM. Oleocanthal inhibits the growth of several breast cancer cell lines at low micromolar concentration in a dose-dependent manner. Oleocanthal treatment caused a marked downregulation of phosphorylated mTOR in metastatic breast cancer cell line (MDA-MB-231). These results strongly indicate that mTOR inhibition is at least one of the factors of the reported anticancer and neuroprotective properties of Oleocanthal. Copyright © 2015 John Wiley & Sons, Ltd.
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olive oil derived Oleocanthal enhances β amyloid clearance as a potential neuroprotective mechanism against alzheimer s disease in vitro and in vivo studies
ACS Chemical Neuroscience, 2013Co-Authors: Alaa H Abuznait, Khalid El A Sayed, Hisham Qosa, Belnaser A Busnena, Amal KaddoumiAbstract:Oleocanthal, a phenolic component of extra-virgin olive oil, has been recently linked to reduced risk of Alzheimer’s disease (AD), a neurodegenerative disease that is characterized by accumulation of β-amyloid (Aβ) and tau proteins in the brain. However, the mechanism by which Oleocanthal exerts its neuroprotective effect is still incompletely understood. Here, we provide in vitro and in vivo evidence for the potential of Oleocanthal to enhance Aβ clearance from the brain via up-regulation of P-glycoprotein (P-gp) and LDL lipoprotein receptor related protein-1 (LRP1), major Aβ transport proteins, at the blood-brain barrier (BBB). Results from in vitro and in vivo studies demonstrated similar and consistent pattern of Oleocanthal in controlling Aβ levels. In cultured mice brain endothelial cells, Oleocanthal treatment increased P-gp and LRP1 expression and activity. Brain efflux index (BEI%) studies of 125I-Aβ40 showed that administration of Oleocanthal extracted from extra-virgin olive oil to C57BL/6 wild...
Amos B Smith - One of the best experts on this subject based on the ideXlab platform.
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Biomimetic Synthesis of Oleocanthal, Oleacein, and Their Analogues Starting from Oleuropein, A Major Compound of Olive Leaves
Journal of Natural Products, 2020Co-Authors: Georgia Sarikaki, Amos B Smith, Nikoleta Christoforidou, Nicolas Gaboriaud-kolar, Ioannis K. Kostakis, Alexios-leandros SkaltsounisAbstract:Oleocanthal and oleacein are known for a wide range of beneficial activities in human health and the prevention of diseases. The inability to isolate significant and pure amounts of these natural c...
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new drugs from ancient natural foods Oleocanthal the natural occurring spicy compound of olive oil a brief history
Drug Discovery Today, 2015Co-Authors: Morena Scotece, Javier Conde, Jesus Pino, Amos B Smith, Vanessa Abella, Verónica López, Francisca Lago, Juan J GomezreinoAbstract:Extra-virgin olive oil (EVOO), a principal component of the Mediterranean diet (Med diet), is one of the most ancient known foods and has long been associated with health benefits. Many phenolic compounds extracted from Olea europea L. have attracted attention since their discovery. Among these phenolic constituents, Oleocanthal has recently emerged as a potential therapeutic molecule for different diseases, showing relevant pharmacological properties in various pathogenic processes, including inflammation, cancers and neurodegenerative diseases. Here, we discuss and summarize the most recent pharmacological evidence for the medical relevance of Oleocanthal, focusing our attention on its anti-inflammatory and chemotherapeutic roles.
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One-Step Semisynthesis of Oleacein and the Determination as a 5-Lipoxygenase Inhibitor
Journal of Natural Products, 2014Co-Authors: Konstantina Vougogiannopoulou, Amos B Smith, Leandros Skaltsounis, Maria Halabalaki, Christelle Lemus, Carlo Pergola, Oliver Werz, Sylvie Michel, Brigitte DeguinAbstract:The dialdehydes oleacein (2) and Oleocanthal (4) are closely related to oleuropein (1) and ligstroside (3), the two latter compounds being abundant iridoids of Olea europaea. By exploiting oleuropein isolated from the plant leaf extract, an efficient procedure has been developed for a one-step semisynthesis of oleacein under Krapcho decarbomethoxylation conditions. Highlighted is the fact that 5-lipoxygenase is a direct target for oleacein with an inhibitory potential (IC50: 2 μM) more potent than Oleocanthal (4) and oleuropein (1). This enzyme catalyzes the initial steps in the biosynthesis of pro-inflammatory leukotrienes. Taken together, the methodology presented here offers an alternative solution to isolation or total synthesis for the procurement of oleacein, thus facilitating the further development as a potential anti-inflammatory agent.
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Oleocanthal Inhibits Proliferation and MIP-1α Expression in Human Multiple Myeloma Cells
Current Medicinal Chemistry, 2013Co-Authors: Morena Scotece, Javier Conde, Amos B Smith, Verónica López, Francisca Lago, Rodolfo Gómez, J. J. Gomez-reino, Oreste GualilloAbstract:Multiple myeloma (MM) is a plasma cell malignancy that causes devastating bone destruction by activating osteoclasts in the bone marrow milieu. MM is the second of all hematological malignancies. Thus, the search for new pharmacological weapons is under intensive investigation being MM a critically important public health goal. Recently, it has been demonstrated that macrophage inflammatory protein 1- alpha (MIP-1α) is crucially involved in the development of osteolytic bone lesions in MM. Phenolic components of extra virgin olive oil are reported to have anti tumor activity. However, the underlying mechanisms and specific targets of extra virgin olive oil remain to be elucidated. In the present study, we investigated the effects of a recently isolated novel extra virgin olive oil polyphenol, Oleocanthal, on the human multiple myeloma cell line ARH-77. Here we report that this natural compound has a remarkable in vitro activity by inhibiting MIP-1α expression and secretion in MM cells. In addition, we also demonstrated that Oleocanthal inhibits MM cells proliferation by inducing the activation of apoptosis mechanisms and by down-regulating ERK1/2 and AKT signal transduction pathways. This in vitro study suggests a therapeutic potential of Oleocanthal in treating multiple myeloma.
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Further evidence for the anti-inflammatory activity of Oleocanthal: inhibition of MIP-1α and IL-6 in J774 macrophages and in ATDC5 chondrocytes.
Life Sciences, 2012Co-Authors: Morena Scotece, Javier Conde, Amos B Smith, Verónica López, Francisca Lago, Rodolfo Gómez, Juan J Gómez-reino, Oreste GualilloAbstract:Abstract Aims Given the relevance of degenerative joint diseases in our society, the development of a novel pharmacologic intervention is a critically important public health goal. Recently, Oleocanthal, a polyphenolic natural compound from extra virgin olive oil, has emerged as a potential therapeutic weapon for the treatment of inflammatory degenerative diseases. The goal of this study was to further evaluate the anti-inflammatory activity of Oleocanthal in murine macrophages J774 and murine chondrocytes ATDC5 with a particular focus on the inhibition of gene expression of pro-inflammatory factors such as MIP-1α and IL-6. Main methods ATDC5 murine chondrogenic cells and murine macrophages J774 were used. J774 macrophages were tested with different doses of Oleocanthal and cell viability was evaluated using the MTT assay. Western blot analysis was carried on in J774 cells using anti NOS2 antibody. Nitrite accumulation was determined in culture supernatant using the Griess reaction. MIP-1α and IL-6 mRNA levels were determined using SYBR Green-based quantitative RT-PCR. MIP-1α and IL-6 protein levels were evaluated using specific ELISA assay. Several cytokines, involved in the inflammatory response, were also tested by BioPlex assay. Key findings First, Oleocanthal inhibits LPS-induced NO production in J774 macrophages, without affecting cell viability. Moreover, it inhibits MIP-1α and IL-6 mRNA expression, as well as protein synthesis, in both ATDC5 chondrocytes and J774 macrophages. Oleocanthal also inhibits IL-1β, TNF-α and GM-CSF protein synthesis from LPS-stimulated macrophages. Significance Our data confirm a clear potent role of Oleocanthal as anti-inflammatory therapeutic agent for future treatment of arthritis or other inflammatory diseases.
Amal Kaddoumi - One of the best experts on this subject based on the ideXlab platform.
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Chemical structures of major EVOO phenolics.
2019Co-Authors: Abu Bakar Siddique, Amal Kaddoumi, Hassan Ebrahim, Mohamed Mohyeldin, Mohammed Qusa, Yazan Batarseh, Ahmed Fayyad, Afsana Tajmim, Sami Nazzal, Khalid El SayedAbstract:S-Oleocanthal (OC), S-HydroxyOleocanthal (HOC), S-Ligstroside aglycone (LA), S-Oleuropein aglycone (OA), Tyrosol (TY), Hydroxytyrosol (HT), (+)-Pinoresinol (PR), (+)-1-Acetoxypinoresinol (APR).
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Application of OC-water isolation method on the Governor EVOO batch number: 5–214000242017.
2019Co-Authors: Abu Bakar Siddique, Amal Kaddoumi, Hassan Ebrahim, Mohamed Mohyeldin, Mohammed Qusa, Yazan Batarseh, Ahmed Fayyad, Afsana Tajmim, Sami Nazzal, Khalid El SayedAbstract:A. Oleocanthal standard calibration curve using quantitative HPLC data. B. HPLC Monitoring of water extraction process; i) HPLC chromatogram for crude EVOO and EVOO after water extraction. ii) HPLC chromatogram of the 1st -3rd water extraction. C. OC standard calibration curve using q1H NMR data. D. 1H NMR-based monitoring of the extraction process. i) 1H NMR spectrum of crude water extract showing OC as a major EVOO phenolic ingredient. ii) Pure OC 1H NMR spectrum after Sephadex LH20 purification.
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Oleocanthalic Acid, a Chemical Marker of Olive Oil Aging and Exposure to a High Storage Temperature with Potential Neuroprotective Activity.
Journal of Agricultural and Food Chemistry, 2018Co-Authors: Annia Tsolakou, Amal Kaddoumi, Eleni Melliou, Feliciano Priego-capote, Panagiotis Diamantakos, Iliana Kalaboki, A. Mena-bravo, Ihab M. Abdallah, Prokopios MagiatisAbstract:The investigation of olive oils stored for a period of 24 months under appropriate conditions (25 °C, dark place, and airtight container) led to the identification of a new major phenolic ingredient, which was named Oleocanthalic acid. The structure of the new compound was elucidated using one- and two-dimensional nuclear magnetic resonance in combination with tandem mass spectrometry. The new compound is an oxidation product of Oleocanthal and is found in fresh oils in very low concentrations. The concentration of Oleocanthalic acid increased with storage time, while the Oleocanthal concentration decreased. A similar increase of the Oleocanthalic acid/Oleocanthal ratio was achieved after exposure of olive oil to 60 °C for 14 days. Although the presence of an oxidized derivative of decarboxymethylated ligstroside aglycon had been reported, it is the first time that its structure is characterized. The isolated compound could induce the expression of amyloid-β major transport proteins as well as tight junct...
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Oleocanthalic Acid, a Chemical Marker of Olive Oil Aging and Exposure to a High Storage Temperature with Potential Neuroprotective Activity
2018Co-Authors: Annia Tsolakou, Amal Kaddoumi, Eleni Melliou, Feliciano Priego-capote, Panagiotis Diamantakos, Iliana Kalaboki, A. Mena-bravo, Ihab M. Abdallah, Prokopios MagiatisAbstract:The investigation of olive oils stored for a period of 24 months under appropriate conditions (25 °C, dark place, and airtight container) led to the identification of a new major phenolic ingredient, which was named Oleocanthalic acid. The structure of the new compound was elucidated using one- and two-dimensional nuclear magnetic resonance in combination with tandem mass spectrometry. The new compound is an oxidation product of Oleocanthal and is found in fresh oils in very low concentrations. The concentration of Oleocanthalic acid increased with storage time, while the Oleocanthal concentration decreased. A similar increase of the Oleocanthalic acid/Oleocanthal ratio was achieved after exposure of olive oil to 60 °C for 14 days. Although the presence of an oxidized derivative of decarboxymethylated ligstroside aglycon had been reported, it is the first time that its structure is characterized. The isolated compound could induce the expression of amyloid-β major transport proteins as well as tight junctions expressed at the blood–brain barrier, suggesting that Oleocanthalic acid could be beneficial against Alzheimer’s disease
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Oleocanthal-rich extra-virgin olive oil enhances donepezil effect by reducing amyloid-β load and related toxicity in a mouse model of Alzheimer’s disease
Journal of Nutritional Biochemistry, 2017Co-Authors: Yazan S. Batarseh, Amal KaddoumiAbstract:Previous evidence suggested that extra-virgin olive oil (EVOO) is linked to attenuating amyloid-β (Aβ) pathology and improving cognitive function in Alzheimer's disease (AD) mouse models. In addition, we recently reported the beneficial effect of Oleocanthal, a phenolic compound in EVOO, against AD pathology. Currently, medications available to target AD pathology are limited. Donepezil is an acetylcholine esterase inhibitor approved for use for all AD stages. Donepezil has been reported to have limited Aβ-targeting mechanisms beside its acetylcholine esterase inhibition. The aim of this study was to investigate the consumption of EVOO rich with Oleocanthal (hereafter EVOO) as a medical food on enhancing the effect of donepezil on attenuating Aβ load and related toxicity in 5xFAD mouse model of AD. Our results showed that EVOO consumption in combination with donepezil significantly reduced Aβ load and related pathological changes. Reduced Aβ load could be explained, at least in part, by enhancing Aβ clearance pathways including blood-brain barrier (BBB) clearance and enzymatic degradation, and shifting amyloid precursor protein processing toward the nonamyloidogenic pathway. Furthermore, EVOO combination with donepezil up-regulated synaptic proteins, enhanced BBB tightness and reduced neuroinflammation associated with Aβ pathology. In conclusion, EVOO consumption as a medical food combined with donepezil offers an effective therapeutic approach by enhancing the noncholinergic mechanisms of donepezil and by providing additional mechanisms to attenuate Aβ-related pathology in AD patients.
Brandon J. English - One of the best experts on this subject based on the ideXlab platform.
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Synthesis of (+/-)-Oleocanthal via a Tandem Intramolecular Michael Cyclization-HWE Olefination.
Tetrahedron Letters, 2009Co-Authors: Brandon J. English, Robert M. WilliamsAbstract:Abstract A synthesis of racemic Oleocanthal has been accomplished in 11 steps from 1,3 propanediol by a key tandem intramolecular Michael cyclization–Horner–Wadsworth–Emmons olefination.
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synthesis of Oleocanthal via a tandem intramolecular michael cyclization hwe olefination
Tetrahedron Letters, 2009Co-Authors: Brandon J. English, Robert M. WilliamsAbstract:Abstract A synthesis of racemic Oleocanthal has been accomplished in 11 steps from 1,3 propanediol by a key tandem intramolecular Michael cyclization–Horner–Wadsworth–Emmons olefination.
