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Olive Bioactives, Nutraceuticals and Health

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (15 November 2018) | Viewed by 43161

Special Issue Editors

IRESMO Foundation, Institute for Research in Europe on Molecular Sciences, c/o DIMEG, 42C, UniCal, 87036 Arcavacata, CS, Italy
Interests: olive bioactives; biomolecular sciences of Mediterranean food; molecular dynamics and computation of Mediterranean bioactives; Mediterranean nutraceuticals; Mediterranean functional foods; Mediterranean cosmeceuticals and nutricosmeceuticals; biophenols; biophenol-secoiridoids; soft-mass spectrometry; heterocyclic molecules; reaction mechanisms of gas-phase organic ions; pericyclic sintones
Rural Clinical School, Faculty of Medicine, University of New South Wales, Wagga Wagga, NSW 2650, Australia
Interests: Alzheimer's disease; dementia; amyloid; Tau; Biomarkers; small molecules; natural products; biophenols; Mediterranean diet
Special Issues, Collections and Topics in MDPI journals
Department of Engineering Technology, College of Technology, University of Houston, Houston, TX 77204, USA
Interests: molecular biotechnology; synthetic biotechnology; natural products; analytical chemistry; medicinal chemistry; computational biotechnology, food engineering and nutra food and medicine

Special Issue Information

Dear Colleagues,

Healthy olive trees, found around the Mediterranean Basin, and then almost worldwide, have an ancient talent, which has been partially recognized by biomolecular sciences. The secret is the complex and beautiful systems of different phytomolecules, such as olive bioactives (OBs). These relatively small biomolecules are significant for wellbeing and health practice of modern Homo edens (eating consumers). Their biomolecular dynamics of pathogen antagonism, before being harvested and processed into olive oil, table olives, and leaf extracts (towards functional foods, nutraceuticals, prevention and the treatment of diseases and the promotion of human health) have still not been precisely investigated and rationalized. Olive-tree processing products are olive oil, table olive, olive waste water and pomace, and olive cell and bioreactor cultures. They contain triacylglycerols, fatty acids, phospholipids, amino acids, sugars, aliphatic and aromatic alcohols, hydrocarbons, biophenols, coumarins, flavonoids, and their glucosides, hydroxy-isochromans, irridoids, secoiridoids, lignans, methoxyphenols, biophenolic fatty acid esters, pigments, sterols, tocopherols, terpenes and volatiles. Some OBs are phytoalexins or phytoanticipins, which can be stored as masked precursors and elicited by host enzymes after pathogen attacks or tissue damages, during olive-milling practice.

Biomolecular evidence refers to many OB groups and subgroups, individual bio- and techno-derivatives, embodying an exceptional font of ingredients for traditional and functional Mediterranean foods, nutraceuticals, cosmeceuticals, and nutricosmeceuticals. The biological action of OBs derives from skillful olive drupe processing and leaf extractions, guaranteed throughout the food supply chain, from the olive orchard to the table, and health supplements. The potential OB impact on modern Homo edens well-being and health arouses attention regarding the prevention and handling of modern degenerative diseases, cancer, cardio- and cerebral-vascular syndromes, as well as bacterial and fungal infections.

This Special Issue intends to re-evaluate OB operative roles, which are exerted in olive drupes and leaves during their transformation into olive oil, table olives, and olive leaf extracts for discovering novel potential influences on Homo edens wellbeing and health. This special issue will be dedicated to understanding how OBs are biosynthesized by using analytical and computational techniques. It will also be beneficial for identifying molecular structures, mechanisms, and functions, as well as the best manufacturing practices to enhance the level of OBs in food and health products to prevent various Homo edens diseases. Increasingly-popular OB-derived dietary supplements require establishing bioavailability, safe concentrations, and potential action on degenerative diseases. OB names sometime have bizarre and commercial terms. A rational method should adopt common or IUPAC names for scientific communication.

Dr. Nicola A. Uccella
Dr. Syed Haris Omar
Dr. Ganapathy Sivakumar
Guest Editors

Manuscript Submission Information

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Keywords

  • Olive Biophenols
  • Olive flavonoids
  • Olive sterols
  • Olive tocopherols
  • Olive terpenes
  • Olive n-3, n-7, n-9 fatty acids
  • Olive volatiles
  • Olive Antioxidant
  • Olive Biological Activity
  • Olive Health Benefits

Published Papers (8 papers)

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Research

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17 pages, 2102 KiB  
Article
Downregulation of Pro-Inflammatory and Pro-Angiogenic Pathways in Prostate Cancer Cells by a Polyphenol-Rich Extract from Olive Mill Wastewater
by Denisa Baci, Matteo Gallazzi, Caterina Cascini, Matilde Tramacere, Daniela De Stefano, Antonino Bruno, Douglas M. Noonan and Adriana Albini
Int. J. Mol. Sci. 2019, 20(2), 307; https://doi.org/10.3390/ijms20020307 - 14 Jan 2019
Cited by 32 | Viewed by 3742
Abstract
Dietary phytochemicals are particularly attractive for chemoprevention and are able to modulate several signal transduction pathways linked with cancer. Olive oil, a major component of the Mediterranean diet, is an abundant source of phenolic compounds. Olive oil production is associated with the generation [...] Read more.
Dietary phytochemicals are particularly attractive for chemoprevention and are able to modulate several signal transduction pathways linked with cancer. Olive oil, a major component of the Mediterranean diet, is an abundant source of phenolic compounds. Olive oil production is associated with the generation of a waste material, termed ‘olive mill wastewater’ (OMWW) that have been reported to contain water-soluble polyphenols. Prostate cancer (PCa) is considered as an ideal cancer type for chemopreventive approaches, due to its wide incidence but relatively long latency period and progression time. Here, we investigated activities associated with potential preventive properties of a polyphenol-rich olive mill wastewater extract, OMWW (A009), on three in vitro models of PCa. A009 was able to inhibit PCa cell proliferation, adhesion, migration, and invasion. Molecularly, we found that A009 targeted NF-κB and reduced pro-angiogenic growth factor, VEGF, CXCL8, and CXCL12 production. IL-6/STAT3 axis was also regulated by the extract. A009 shows promising properties, and purified hydroxytyrosol (HyT), the major polyphenol component of A009, was also active but not always as effective as A009. Finally, our results support the idea of repositioning a food waste-derived material for nutraceutical employment, with environmental and industrial cost management benefits. Full article
(This article belongs to the Special Issue Olive Bioactives, Nutraceuticals and Health)
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23 pages, 4241 KiB  
Article
Olive Biophenols Reduces Alzheimer’s Pathology in SH-SY5Y Cells and APPswe Mice
by Syed Haris Omar, Christopher J. Scott, Adam S. Hamlin and Hassan K. Obied
Int. J. Mol. Sci. 2019, 20(1), 125; https://doi.org/10.3390/ijms20010125 - 30 Dec 2018
Cited by 42 | Viewed by 6571
Abstract
Alzheimer’s disease (AD) is a major neurodegenerative disease, associated with the hallmark proteinacious constituent called amyloid beta (Aβ) of senile plaques. Moreover, it is already established that metals (particularly copper, zinc and iron) have a key role in the pathogenesis of AD. In [...] Read more.
Alzheimer’s disease (AD) is a major neurodegenerative disease, associated with the hallmark proteinacious constituent called amyloid beta (Aβ) of senile plaques. Moreover, it is already established that metals (particularly copper, zinc and iron) have a key role in the pathogenesis of AD. In order to reduce the Aβ plaque burden and overcome the side effects from the synthetic inhibitors, the current study was designed to focus on direct inhibition of with or without metal-induced Aβ fibril formation and aggregation by using olive biophenols. Exposure of neuroblastoma (SH-SY5Y) cells with Aβ42 resulted in decrease of cell viability and morphological changes might be due to severe increase in the reactive oxygen species (ROS). The pre-treated SH-SY5Y cells with olive biophenols were able to attenuate cell death caused by Aβ42, copper- Aβ42, and [laevodihydroxyphenylalanine (l-DOPA)] l-DOPA-Aβ42-induced toxicity after 24 h of treatment. Oleuropein, verbascoside and rutin were the major anti-amyloidogenic compounds. Transgenic mice (APPswe/PS1dE9) received 50 mg/kg of oleuropein containing olive leaf extracts (OLE) or control diet from 7 to 23 weeks of age. Treatment mice (OLE) were showed significantly reduced amyloid plaque deposition (p < 0.001) in cortex and hippocampus as compared to control mice. Our findings provide a basis for considering natural and low cost biophenols from olive as a promising candidate drug against AD. Further studies warrant to validate and determine the anti-amyloid mechanism, bioavailability as well as permeability of olive biophenols against blood brain barrier in AD. Full article
(This article belongs to the Special Issue Olive Bioactives, Nutraceuticals and Health)
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12 pages, 2340 KiB  
Article
Oleuropein Induces AMPK-Dependent Autophagy in NAFLD Mice, Regardless of the Gender
by Cristiana Porcu, Silvia Sideri, Maurizio Martini, Alessandra Cocomazzi, Andrea Galli, Giovanni Tarantino and Clara Balsano
Int. J. Mol. Sci. 2018, 19(12), 3948; https://doi.org/10.3390/ijms19123948 - 08 Dec 2018
Cited by 37 | Viewed by 4997
Abstract
Oleuropein (Ole) is one of the most plentiful phenolic compounds with antioxidant, anti-inflammatory, anti-atherogenic, hypoglycemic and hypolipidemic effects. The aim of our study was to establish whether the positive Ole-related effects on liver steatosis could be associated with autophagy. Female and male C57BL/6J [...] Read more.
Oleuropein (Ole) is one of the most plentiful phenolic compounds with antioxidant, anti-inflammatory, anti-atherogenic, hypoglycemic and hypolipidemic effects. The aim of our study was to establish whether the positive Ole-related effects on liver steatosis could be associated with autophagy. Female and male C57BL/6J mice were fed normal diet (ND) or high-fat diet (HFD) for eight weeks, and Ole was added or not for the following eight weeks. The autophagy-related proteins Akt, mTOR, AMPK, ULK1, Beclin-1, LC3B and p62/Sqstm1 were analyzed. Interestingly, Ole induced a different regulation of the Akt/mTOR pathway in female compared to male mice, but was able to activate the autophagic process in ND and HFD mice through AMPK-dependent phosphorylation of ULK1 at Ser555, regardless of the gender. Our work reveals the ability of Ole to induce, in liver of ND and HFD mice, autophagy independently by gender-specific mTOR activation. We highlight Ole as a novel therapeutic approach to counteract unhealthy diet-related liver steatosis by targeting autophagy. Full article
(This article belongs to the Special Issue Olive Bioactives, Nutraceuticals and Health)
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14 pages, 10265 KiB  
Article
Probing Downstream Olive Biophenol Secoiridoids
by Ganapathy Sivakumar, Nicola A. Uccella and Luigi Gentile
Int. J. Mol. Sci. 2018, 19(10), 2892; https://doi.org/10.3390/ijms19102892 - 23 Sep 2018
Cited by 8 | Viewed by 4114
Abstract
Numerous bioactive biophenol secoiridoids (BPsecos) are found in the fruit, leaves, and oil of olives. These BPsecos play important roles in both the taste of food and human health. The main BPseco bioactive from green olive fruits, leaves, and table olives is oleuropein, [...] Read more.
Numerous bioactive biophenol secoiridoids (BPsecos) are found in the fruit, leaves, and oil of olives. These BPsecos play important roles in both the taste of food and human health. The main BPseco bioactive from green olive fruits, leaves, and table olives is oleuropein, while olive oil is rich in oleuropein downstream pathway molecules. The aim of this study was to probe olive BPseco downstream molecular pathways that are alike in biological and olive processing systems at different pHs and reaction times. The downstream molecular pathway were analyzed by high performance liquid chromatography coupled with electrospray ionization mass spectrometry (HPLC-ESI/MS) and typed neglected of different overlap (TNDO) computational methods. Our study showed oleuropein highest occupied molecular orbital (HOMO) and HOMO-1 triggered the free radical processes, while HOMO-2 and lowest unoccupied molecular orbital (LUMO) were polar reactions of glucoside and ester groups. Olive BPsecos were found to be stable under acid and base catalylic experiments. Oleuropein aglycone opened to diales and rearranged to hydroxytyrosil-elenolate under strong reaction conditions. The results suggest that competition among olive BPseco HOMOs could induce glucoside hydrolysis during olive milling due to native olive β-glucosidases. The underlined olive BPsecos downstream molecular mechanism herein could provide new insights into the olive milling process to improve BPseco bioactives in olive oil and table olives, which would enhance both the functional food and the nutraceuticals that are produced from olives. Full article
(This article belongs to the Special Issue Olive Bioactives, Nutraceuticals and Health)
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25 pages, 12459 KiB  
Article
A Proteomic Approach to Uncover Neuroprotective Mechanisms of Oleocanthal against Oxidative Stress
by Laura Giusti, Cristina Angeloni, Maria Cristina Barbalace, Serena Lacerenza, Federica Ciregia, Maurizio Ronci, Andrea Urbani, Clementina Manera, Maria Digiacomo, Marco Macchia, Maria Rosa Mazzoni, Antonio Lucacchini and Silvana Hrelia
Int. J. Mol. Sci. 2018, 19(8), 2329; https://doi.org/10.3390/ijms19082329 - 08 Aug 2018
Cited by 39 | Viewed by 4525
Abstract
Neurodegenerative diseases represent a heterogeneous group of disorders that share common features like abnormal protein aggregation, perturbed Ca2+ homeostasis, excitotoxicity, impairment of mitochondrial functions, apoptosis, inflammation, and oxidative stress. Despite recent advances in the research of biomarkers, early diagnosis, and pharmacotherapy, there [...] Read more.
Neurodegenerative diseases represent a heterogeneous group of disorders that share common features like abnormal protein aggregation, perturbed Ca2+ homeostasis, excitotoxicity, impairment of mitochondrial functions, apoptosis, inflammation, and oxidative stress. Despite recent advances in the research of biomarkers, early diagnosis, and pharmacotherapy, there are no treatments that can halt the progression of these age-associated neurodegenerative diseases. Numerous epidemiological studies indicate that long-term intake of a Mediterranean diet, characterized by a high consumption of extra virgin olive oil, correlates with better cognition in aged populations. Olive oil phenolic compounds have been demonstrated to have different biological activities like antioxidant, antithrombotic, and anti-inflammatory activities. Oleocanthal, a phenolic component of extra virgin olive oil, is getting more and more scientific attention due to its interesting biological activities. The aim of this research was to characterize the neuroprotective effects of oleocanthal against H2O2-induced oxidative stress in neuron-like SH-SY5Y cells. Moreover, protein expression profiling, combined with pathways analyses, was used to investigate the molecular events related to the protective effects. Oleocanthal was demonstrated to counteract oxidative stress, increasing cell viability, reducing reactive oxygen species (ROS) production, and increasing reduced glutathione (GSH) intracellular level. Proteomic analysis revealed that oleocanthal significantly modulates 19 proteins in the presence of H2O2. In particular, oleocanthal up-regulated proteins related to the proteasome, the chaperone heat shock protein 90, the glycolytic enzyme pyruvate kinase, and the antioxidant enzyme peroxiredoxin 1. Moreover, oleocanthal protection seems to be mediated by Akt activation. These data offer new insights into the molecular mechanisms behind oleocanthal protection against oxidative stress. Full article
(This article belongs to the Special Issue Olive Bioactives, Nutraceuticals and Health)
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17 pages, 2718 KiB  
Article
The Olive Biophenols Oleuropein and Hydroxytyrosol Selectively Reduce Proliferation, Influence the Cell Cycle, and Induce Apoptosis in Pancreatic Cancer Cells
by Chloe D. Goldsmith, Danielle R. Bond, Helen Jankowski, Judith Weidenhofer, Costas E. Stathopoulos, Paul D. Roach and Christopher J. Scarlett
Int. J. Mol. Sci. 2018, 19(7), 1937; https://doi.org/10.3390/ijms19071937 - 02 Jul 2018
Cited by 77 | Viewed by 5455
Abstract
Current chemotherapy drugs for pancreatic cancer only offer an increase in survival of up to six months. Additionally, they are highly toxic to normal tissues, drastically affecting the quality of life of patients. Therefore, the search for novel agents, which induce apoptosis in [...] Read more.
Current chemotherapy drugs for pancreatic cancer only offer an increase in survival of up to six months. Additionally, they are highly toxic to normal tissues, drastically affecting the quality of life of patients. Therefore, the search for novel agents, which induce apoptosis in cancer cells while displaying limited toxicity towards normal cells, is paramount. The olive biophenols, oleuropein, hydroxytyrosol and tyrosol, have displayed cytotoxicity towards cancer cells without affecting non-tumorigenic cells in cancers of the breast and prostate. However, their activity in pancreatic cancer has not been investigated. Therefore, the aim of this study was to determine the anti-pancreatic cancer potential of oleuropein, hydroxytyrosol and tyrosol. Pancreatic cancer cells (MIA PaCa-2, BxPC-3, and CFPAC-1) and non-tumorigenic pancreas cells (HPDE) were treated with oleuropein, hydroxytyrosol and tyrosol to determine their effect on cell viability. Oleuropein displayed selective toxicity towards MIA PaCa-2 cells and hydroxytyrosol towards MIA PaCa-2 and HPDE cells. Subsequent analysis of Bcl-2 family proteins and caspase 3/7 activation determined that oleuropein and hydroxytyrosol induced apoptosis in MIA PaCa-2 cells, while oleuropein displayed a protective effect on HPDE cells. Gene expression analysis revealed putative mechanisms of action, which suggested that c-Jun and c-Fos are involved in oleuropein and hydroxytyrosol induced apoptosis of MIA PaCa-2 cells. Full article
(This article belongs to the Special Issue Olive Bioactives, Nutraceuticals and Health)
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Review

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13 pages, 1678 KiB  
Review
Olive Tree Biophenols in Inflammatory Bowel Disease: When Bitter is Better
by Tiziana Larussa, Maria Imeneo and Francesco Luzza
Int. J. Mol. Sci. 2019, 20(6), 1390; https://doi.org/10.3390/ijms20061390 - 20 Mar 2019
Cited by 27 | Viewed by 4846
Abstract
The current therapeutic scenario for inflammatory bowel diseases (IBD) involves aminosalicylates, corticosteroids, and immunomodulators, but concerns regarding their safety profiles and high costs heavily impact their widespread use. In recent years, the beneficial effects thatbiophenols—from fruit and vegetables—have on human health have been [...] Read more.
The current therapeutic scenario for inflammatory bowel diseases (IBD) involves aminosalicylates, corticosteroids, and immunomodulators, but concerns regarding their safety profiles and high costs heavily impact their widespread use. In recent years, the beneficial effects thatbiophenols—from fruit and vegetables—have on human health have been investigated. The antioxidant and anti-inflammatory properties of phenolic fraction, from olive leaves and fruits, have been suggested, and a potential application in gut inflammation has been supported by in vitro and IBD-animal models studies. In the present review, we first introduced the potential therapeutic role of olive tree biophenolsin chronic inflammatory disease. Then, we aimed to describe their most interesting application for gut inflammation, as the results of basic science studies and animal experimental models. Finally, the potential role of olive tree biophenols in the setting of human IBD is discussed. Full article
(This article belongs to the Special Issue Olive Bioactives, Nutraceuticals and Health)
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15 pages, 713 KiB  
Review
Olive Oil Nutraceuticals in the Prevention and Management of Diabetes: From Molecules to Lifestyle
by Ahmad Alkhatib, Catherine Tsang and Jaakko Tuomilehto
Int. J. Mol. Sci. 2018, 19(7), 2024; https://doi.org/10.3390/ijms19072024 - 12 Jul 2018
Cited by 40 | Viewed by 7974
Abstract
Lifestyle is the primary prevention of diabetes, especially type-2 diabetes (T2D). Nutritional intake of olive oil (OO), the key Mediterranean diet component has been associated with the prevention and management of many chronic diseases including T2D. Several OO bioactive compounds such as monounsaturated [...] Read more.
Lifestyle is the primary prevention of diabetes, especially type-2 diabetes (T2D). Nutritional intake of olive oil (OO), the key Mediterranean diet component has been associated with the prevention and management of many chronic diseases including T2D. Several OO bioactive compounds such as monounsaturated fatty acids, and key biophenols including hydroxytyrosol and oleuropein, have been associated with preventing inflammation and cytokine-induced oxidative damage, glucose lowering, reducing carbohydrate absorption, and increasing insulin sensitivity and related gene expression. However, research into the interaction of OO nutraceuticals with lifestyle components, especially physical activity, is lacking. Promising postprandial effects have been reported when OO or other similar monounsaturated fatty acids were the main dietary fat compared with other diets. Animal studies have shown a potential anabolic effect of oleuropein. Such effects could be further potentiated via exercise, especially strength training, which is an essential exercise prescription for individuals with T2D. There is also an evidence from in vitro, animal, and limited human studies for a dual preventative role of OO biophenols in diabetes and cancer, especially that they share similar risk factors. Putative antioxidative and anti-inflammatory mechanisms and associated gene expressions resulting from OO biophenols have produced paradoxical results, making suggested inferences from dual prevention T2D and cancer outcomes difficult. Well-designed human interventions and clinical trials are needed to decipher such a potential dual anticancer and antidiabetic effects of OO nutraceuticals. Exercise combined with OO consumption, individually or as part of a healthy diet is likely to induce reciprocal action for T2D prevention outcomes. Full article
(This article belongs to the Special Issue Olive Bioactives, Nutraceuticals and Health)
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