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Olivares-Vicente M, Sánchez-Marzo N, Herranz-López M, Micol V. Analysis of Lemon Verbena Polyphenol Metabolome and Its Correlation with Oxidative Stress under Glucotoxic Conditions in Adipocyte. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:9768-9781. [PMID: 38629896 PMCID: PMC11066870 DOI: 10.1021/acs.jafc.3c06309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 03/21/2024] [Accepted: 03/26/2024] [Indexed: 05/02/2024]
Abstract
Lemon verbena has been shown to ameliorate obesity-related oxidative stress, but the intracellular final effectors underlying its antioxidant activity are still unknown. The purpose of this study was to correlate the antioxidant capacity of plasma metabolites of lemon verbena (verbascoside, isoverbascoside, hydroxytyrosol, caffeic acid, ferulic acid, homoprotocatechuic acid, and luteolin-7-diglucuronide) with their uptake and intracellular metabolism in hypertrophic adipocytes under glucotoxic conditions. To this end, intracellular ROS levels were measured, and the intracellular metabolites were identified and quantified by high-performance liquid chromatography with a diode array detector coupled to mass spectrometry (HPLC-DAD-MS). The results showed that the plasma metabolites of lemon verbena are absorbed by adipocytes and metabolized through phase II reactions and that the intracellular appearance of these metabolites correlates with the decrease in the level of glucotoxicity-induced oxidative stress. It is postulated that the biotransformation and accumulation of these metabolites in adipocytes contribute to the long-term antioxidant activity of the extract.
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Affiliation(s)
- Mariló Olivares-Vicente
- Instituto
de Investigación, Desarrollo e Innovación en Biotecnología
Sanitaria de Elche, Universidad Miguel Hernández
(UMH), Elche 03202, Spain
| | - Noelia Sánchez-Marzo
- Instituto
de Investigación, Desarrollo e Innovación en Biotecnología
Sanitaria de Elche, Universidad Miguel Hernández
(UMH), Elche 03202, Spain
| | - María Herranz-López
- Instituto
de Investigación, Desarrollo e Innovación en Biotecnología
Sanitaria de Elche, Universidad Miguel Hernández
(UMH), Elche 03202, Spain
| | - Vicente Micol
- Instituto
de Investigación, Desarrollo e Innovación en Biotecnología
Sanitaria de Elche, Universidad Miguel Hernández
(UMH), Elche 03202, Spain
- CIBER:
CB12/03/30038, Fisiopatología de la Obesidad y la Nutrición,
CIBERobn, Instituto de Salud Carlos III
(ISCIII), Madrid 28029, Spain
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2
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Decot H, Sudhakaran M, Boismier E, Schilmiller A, Claucherty E, Doseff AI, Aliakbarian B. Tart Cherry ( Prunus cerasus L.) Pit Extracts Protect Human Skin Cells against Oxidative Stress: Unlocking Sustainable Uses for Food Industry Byproducts. Foods 2023; 12:3748. [PMID: 37893640 PMCID: PMC10606708 DOI: 10.3390/foods12203748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 09/25/2023] [Accepted: 10/07/2023] [Indexed: 10/29/2023] Open
Abstract
Industrial processing of tart cherries (Prunus cerasus L.) produces bioproducts like cherry pits (CP), which contribute to adverse environmental effects. To identify sustainable strategies to minimize the environmental impact of cherry processing, we investigated their potential value as antioxidants for prospective utilization within cosmeceutical applications. Untargeted metabolomic analyses of water and water: ethanol CP extracts using an eco-friendly technique revealed significant enrichment in coumaroyl derivatives and flavonoids with congruent metabolite representation regardless of the extraction solvent. The antioxidant activity of tart CP extracts was evaluated on human skin cells exposed to H2O2 or LPS, modeling environmentally induced oxidants. Notably, both CP extracts provide antioxidant activity by reducing H2O2 or LPS-induced ROS in human skin keratinocytes without affecting cell viability. The CP extracts increased the expression of CAT and SOD1 genes encoding antioxidant regulatory enzymes while decreasing the expression of NOS2, a pro-oxidant regulator. These findings reveal the antioxidant properties of tart CP, offering new opportunities to produce natural-based skin care products and adding economic value while providing sustainable options to reduce the environmental impact of food byproducts.
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Affiliation(s)
- Hannah Decot
- Molecular, Cellular, and Integrative Physiology Graduate Program, Michigan State University, 567 Wilson Rd., East Lansing, MI 48824, USA; (H.D.); (M.S.)
- Department of Physiology, Michigan State University, 567 Wilson Rd., East Lansing, MI 48824, USA;
| | - Meenakshi Sudhakaran
- Molecular, Cellular, and Integrative Physiology Graduate Program, Michigan State University, 567 Wilson Rd., East Lansing, MI 48824, USA; (H.D.); (M.S.)
- Department of Physiology, Michigan State University, 567 Wilson Rd., East Lansing, MI 48824, USA;
| | - Emma Boismier
- Department of Physiology, Michigan State University, 567 Wilson Rd., East Lansing, MI 48824, USA;
| | - Anthony Schilmiller
- Mass Spectrometry and Metabolomics Core, Michigan State University, 603 Wilson Rd., East Lansing, MI 48824, USA;
| | - Ethan Claucherty
- The Axia Institute, Michigan State University, 1910 W. St. Andrews Rd., Midland, MI 49640, USA;
| | - Andrea I. Doseff
- Department of Physiology, Michigan State University, 567 Wilson Rd., East Lansing, MI 48824, USA;
- Department of Pharmacology and Toxicology, Michigan State University, 1355 Bogue St., East Lasing, MI 48824, USA
| | - Bahar Aliakbarian
- The Axia Institute, Michigan State University, 1910 W. St. Andrews Rd., Midland, MI 49640, USA;
- Department of Biosystems and Agricultural Engineering, Michigan State University, 524 S Shaw Lane, East Lansing, MI 48824, USA
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Vijakumaran U, Shanmugam J, Heng JW, Azman SS, Yazid MD, Haizum Abdullah NA, Sulaiman N. Effects of Hydroxytyrosol in Endothelial Functioning: A Comprehensive Review. Molecules 2023; 28:molecules28041861. [PMID: 36838850 PMCID: PMC9966213 DOI: 10.3390/molecules28041861] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 02/13/2023] [Accepted: 02/14/2023] [Indexed: 02/18/2023] Open
Abstract
Pharmacologists have been emphasizing and applying plant and herbal-based treatments in vascular diseases for decades now. Olives, for example, are a traditional symbol of the Mediterranean diet. Hydroxytyrosol is an olive-derived compound known for its antioxidant and cardioprotective effects. Acknowledging the merit of antioxidants in maintaining endothelial function warrants the application of hydroxytyrosol in endothelial dysfunction salvage and recovery. Endothelial dysfunction (ED) is an impairment of endothelial cells that adversely affects vascular homeostasis. Disturbance in endothelial functioning is a known precursor for atherosclerosis and, subsequently, coronary and peripheral artery disease. However, the effects of hydroxytyrosol on endothelial functioning were not extensively studied, limiting its value either as a nutraceutical supplement or in clinical trials. The action of hydroxytyrosol in endothelial functioning at a cellular and molecular level is gathered and summarized in this review. The favorable effects of hydroxytyrosol in the improvement of endothelial functioning from in vitro and in vivo studies were scrutinized. We conclude that hydroxytyrosol is capable to counteract oxidative stress, inflammation, vascular aging, and arterial stiffness; thus, it is beneficial to preserve endothelial function both in vitro and in vivo. Although not specifically for endothelial dysfunction, hydroxytyrosol safety and efficacy had been demonstrated via in vivo and clinical trials for cardiovascular-related studies.
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Ayyadurai VAS, Deonikar P, Fields C. Mechanistic Understanding of D-Glucaric Acid to Support Liver Detoxification Essential to Muscle Health Using a Computational Systems Biology Approach. Nutrients 2023; 15:733. [PMID: 36771439 PMCID: PMC9921405 DOI: 10.3390/nu15030733] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 01/10/2023] [Accepted: 01/24/2023] [Indexed: 02/04/2023] Open
Abstract
Liver and muscle health are intimately connected. Nutritional strategies that support liver detoxification are beneficial to muscle recovery. Computational-in silico-molecular systems' biology analysis of supplementation of calcium and potassium glucarate salts and their metabolite D-glucaric acid (GA) reveals their positive effect on mitigation of liver detoxification via four specific molecular pathways: (1) ROS production, (2) deconjugation, (3) apoptosis of hepatocytes, and (4) β-glucuronidase synthesis. GA improves liver detoxification by downregulating hepatocyte apoptosis, reducing glucuronide deconjugates levels, reducing ROS production, and inhibiting β-Glucuronidase enzyme that reduces re-absorption of toxins in hepatocytes. Results from this in silico study provide an integrative molecular mechanistic systems explanation for the mitigation of liver toxicity by GA.
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Affiliation(s)
- V. A. Shiva Ayyadurai
- Systems Biology Group, CytoSolve Research Division, CytoSolve, Inc., Cambridge, MA 02138, USA
| | - Prabhakar Deonikar
- Systems Biology Group, CytoSolve Research Division, CytoSolve, Inc., Cambridge, MA 02138, USA
| | - Christine Fields
- Applied Food Sciences Inc., 8708 South Congress Suite 290, Austin, TX 78745, USA
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Pluta R, Furmaga-Jabłońska W, Januszewski S, Czuczwar SJ. Post-Ischemic Brain Neurodegeneration in the Form of Alzheimer's Disease Proteinopathy: Possible Therapeutic Role of Curcumin. Nutrients 2022; 14:nu14020248. [PMID: 35057429 PMCID: PMC8779038 DOI: 10.3390/nu14020248] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Revised: 01/01/2022] [Accepted: 01/03/2022] [Indexed: 02/01/2023] Open
Abstract
For thousands of years, mankind has been using plant extracts or plants themselves as medicinal herbs. Currently, there is a great deal of public interest in naturally occurring medicinal substances that are virtually non-toxic, readily available, and have an impact on well-being and health. It has been noted that dietary curcumin is one of the regulators that may positively influence changes in the brain after ischemia. Curcumin is a natural polyphenolic compound with pleiotropic biological properties. The observed death of pyramidal neurons in the CA1 region of the hippocampus and its atrophy are considered to be typical changes for post-ischemic brain neurodegeneration and for Alzheimer’s disease. Additionally, it has been shown that one of the potential mechanisms of severe neuronal death is the accumulation of neurotoxic amyloid and dysfunctional tau protein after cerebral ischemia. Post-ischemic studies of human and animal brains have shown the presence of amyloid plaques and neurofibrillary tangles. The significant therapeutic feature of curcumin is that it can affect the aging-related cellular proteins, i.e., amyloid and tau protein, preventing their aggregation and insolubility after ischemia. Curcumin also decreases the neurotoxicity of amyloid and tau protein by affecting their structure. Studies in animal models of cerebral ischemia have shown that curcumin reduces infarct volume, brain edema, blood-brain barrier permeability, apoptosis, neuroinflammation, glutamate neurotoxicity, inhibits autophagy and oxidative stress, and improves neurological and behavioral deficits. The available data suggest that curcumin may be a new therapeutic substance in both regenerative medicine and the treatment of neurodegenerative disorders such as post-ischemic neurodegeneration.
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Affiliation(s)
- Ryszard Pluta
- Laboratory of Ischemic and Neurodegenerative Brain Research, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland;
- Correspondence: ; Tel.: +48-22-6086-540
| | - Wanda Furmaga-Jabłońska
- Department of Neonate and Infant Pathology, Medical University of Lublin, 20-093 Lublin, Poland;
| | - Sławomir Januszewski
- Laboratory of Ischemic and Neurodegenerative Brain Research, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland;
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Valdenegro M, Bernales M, Knox M, Vinet R, Caballero E, Ayala-Raso A, Kučerová D, Kumar R, Viktorová J, Ruml T, Figueroa CR, Fuentes L. Characterization of Fruit Development, Antioxidant Capacity, and Potential Vasoprotective Action of Peumo ( Cryptocarya alba), a Native Fruit of Chile. Antioxidants (Basel) 2021; 10:antiox10121997. [PMID: 34943100 PMCID: PMC8698990 DOI: 10.3390/antiox10121997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/07/2021] [Accepted: 12/10/2021] [Indexed: 11/18/2022] Open
Abstract
The peumo (Cryptocarya alba) is a native fruit from central Chile that belongs to the Lauraceae family. To characterize the development and the potential health benefits of this edible fruit, quality and physiological parameters, along with antioxidant capacity, were evaluated during three clearly defined developmental stages of the fruit in two seasons. The most distinguishable attributes of ripe fruit were the change in size and color. Low CO2 production and no detectable ethylene levels suggested non-climacteric behavior of the peumo fruit. Peumo demonstrate a significant increase in their antioxidant capacity per 1 g of fresh weight (FW) of the sample, from small to ripe fruit. Higher values in ripe fruit (FRAP: 37.1–38.3 µmol FeSO4/gFW, TEAC: 7.9–8.1 mmol TE/gFW, DPPH: 8.4-8.7 IC50 μg/mL, and ORAC: = 0.19–0.20 mmol TE/gFW) were observed than those in blueberry fruit (FRAP: 4.95 µmol FeSO4/gFW, TEAC: 1.25 mmol TE/gFW, DPPH: 11.3 IC50 μg/mL, and ORAC: 0.032 mmol TE/ gFW). The methanol extracts of ripe fruit displayed the presence of polyphenol acids and quercetin, an ORAC value of 0.637 ± 0.061 mmol TE per g dried weight (DW), and a high cellular antioxidant and anti-inflammatory potential, the latter exceeding the effect of quercetin and indomethacin used as standard molecules. Also, the assay of isolated rat aorta with endothelium-dependent relaxation damage demonstrated that the peumo extract induced vascular protection, depending on its concentration under a high glucose condition. These results demonstrate that these endemic fruits have a good chance as ingredients or foods with functional properties.
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Affiliation(s)
- Mónika Valdenegro
- Escuela de Agronomía, Facultad de Ciencias Agronómicas y de los Alimentos, Pontificia Universidad Católica de Valparaíso, Casilla 4-D, Quillota 2260000, Chile; (M.V.); (M.B.)
| | - Maricarmen Bernales
- Escuela de Agronomía, Facultad de Ciencias Agronómicas y de los Alimentos, Pontificia Universidad Católica de Valparaíso, Casilla 4-D, Quillota 2260000, Chile; (M.V.); (M.B.)
| | - Marcela Knox
- Laboratory of Pharmacology, Center of Micro Bioinnovation (CMBi), Faculty of Pharmacy, Universidad de Valparaíso, Valparaíso 2360102, Chile; (M.K.); (R.V.)
| | - Raúl Vinet
- Laboratory of Pharmacology, Center of Micro Bioinnovation (CMBi), Faculty of Pharmacy, Universidad de Valparaíso, Valparaíso 2360102, Chile; (M.K.); (R.V.)
- Centro Regional de Estudios en Alimentos Saludables (CREAS), CONICYT-Regional GORE Valparaíso Proyecto R17A10001, Avenida Universidad 330, Placilla, Curauma, Valparaíso 2362696, Chile;
| | - Eduardo Caballero
- Centro Regional de Estudios en Alimentos Saludables (CREAS), CONICYT-Regional GORE Valparaíso Proyecto R17A10001, Avenida Universidad 330, Placilla, Curauma, Valparaíso 2362696, Chile;
| | - Aníbal Ayala-Raso
- Instituto de Estadística, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile;
| | - Denisa Kučerová
- Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague, Czech Republic; (D.K.); (R.K.); (J.V.); (T.R.)
| | - Rohitesh Kumar
- Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague, Czech Republic; (D.K.); (R.K.); (J.V.); (T.R.)
| | - Jitka Viktorová
- Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague, Czech Republic; (D.K.); (R.K.); (J.V.); (T.R.)
| | - Tomáš Ruml
- Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague, Czech Republic; (D.K.); (R.K.); (J.V.); (T.R.)
| | - Carlos R. Figueroa
- Laboratory of Plant Molecular Physiology, Institute of Biological Sciences, Universidad de Talca, Talca 3465548, Chile;
| | - Lida Fuentes
- Centro Regional de Estudios en Alimentos Saludables (CREAS), CONICYT-Regional GORE Valparaíso Proyecto R17A10001, Avenida Universidad 330, Placilla, Curauma, Valparaíso 2362696, Chile;
- Correspondence: ; Tel.: +56-322372868
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Fança-Berthon P, Tenon M, Bouter-Banon SL, Manfré A, Maudet C, Dion A, Chevallier H, Laval J, van Breemen RB. Pharmacokinetics of a Single Dose of Turmeric Curcuminoids Depends on Formulation: Results of a Human Crossover Study. J Nutr 2021; 151:1802-1816. [PMID: 33877323 PMCID: PMC8245892 DOI: 10.1093/jn/nxab087] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 01/11/2021] [Accepted: 03/09/2021] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Curcuminoids from turmeric rhizome have significant health benefits but low bioavailability. OBJECTIVES To assess the pharmacokinetics of a novel natural turmeric dried colloidal suspension compared with 4 other turmeric formulations (including a standardized extract) at their respective recommended dosages. METHODS Thirty healthy men and women (18 to 45 y old) were enrolled in a randomized, open-labeled, crossover trial, and sequentially consumed single oral doses of standard turmeric extract (1500 mg), liquid micellar preparation (1000 mg), piperine-curcuminoid combination (1515 mg), phytosome formulation (1000 mg), or the dried colloidal suspension (300 mg). Eleven blood samples were obtained over 24 h, plasma was extracted with or without deconjugation with β-glucuronidase or sulfatase, and ultra-high-pressure liquid chromatography/tandem MS was used to quantify the 3 parent curcuminoids and 12 metabolites. Classical pharmacokinetics parameters were derived. RESULTS The total AUC values of unconjugated curcuminoids were highly variable within participants, with no significant differences between formulations. However, the AUC values for total curcuminoids (including all metabolites) showed significant product effects. Indeed, the micellar preparation delivered higher levels of total curcuminoids than any other formulation (8540 ng·h/mL), reaching significance when compared with the dried colloidal suspension and standard extract (6520 and 5080 ng·h/mL, respectively). After dose normalization, both micellar and dried colloidal formulations showed significantly higher AUC levels than the standard extract (respectively 136 and 72.9, compared with 3.7 ng·h/mL/mg). Total curcuminoid absorption levels were also significantly higher for the dried colloidal suspension when compared with either piperine or phytosome formulations. Interestingly, no significant differences were observed between the piperine-curcuminoid combination and the standard extract. No serious adverse events were reported. CONCLUSIONS The administration of a low dose of the novel natural dried colloidal suspension provided high unconjugated and conjugated curcuminoid absorption, with significant beneficial differences when compared with the high dose of standard extract.This trial was registered at clinicaltrials.gov as NCT03621865.
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Agulló-Chazarra L, Borrás-Linares I, Lozano-Sánchez J, Segura-Carretero A, Micol V, Herranz-López M, Barrajón-Catalán E. Sweet Cherry Byproducts Processed by Green Extraction Techniques as a Source of Bioactive Compounds with Antiaging Properties. Antioxidants (Basel) 2020; 9:antiox9050418. [PMID: 32414056 PMCID: PMC7278782 DOI: 10.3390/antiox9050418] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Revised: 05/05/2020] [Accepted: 05/10/2020] [Indexed: 12/20/2022] Open
Abstract
In the cosmetic industry, there is a continuous demand for new and innovative ingredients for product development. In the context of continual renovation, both cosmetic companies and customers are particularly interested in compounds derived from natural sources due to their multiple benefits. In this study, novel and green-extractive techniques (pressurized solvent, supercritical CO2, and subcritical water extractions) were used to obtain three new extracts from sweet cherry stems, a byproduct generated by the food industry. The extracts were characterized by high-performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS), and 57 compounds, mainly flavonoids but also organic and phenolic acids, fatty acids, and terpenes, were identified. After analytical characterization, a multistep screening approach, including antioxidant, enzymatic, and photoprotective cellular studies, was used to select the best extract according to its benefits of interest to the cosmetics industry. The extract obtained with supercritical CO2 presented the best characteristics, including a wide antioxidant capacity, especially against lipid peroxyl and •OH free radicals, as well as relevant photoprotective action and antiaging properties, making it a potential new ingredient for consideration in the development of new cosmetics.
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Affiliation(s)
- Luz Agulló-Chazarra
- Instituto de Biología Molecular y Celular (IBMC) and Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universitas Miguel Hernández (UMH), 03202 Elche, Spain; (L.A.-C.); (V.M.); (E.B.-C.)
| | - Isabel Borrás-Linares
- Research and Development Functional Food Centre (CIDAF), Health Science Technological Park, Avenida del Conocimiento 37, BioRegión Building, 18016 Granada, Spain; (I.B.-L.); (J.L.-S.); (A.S.-C.)
| | - Jesús Lozano-Sánchez
- Research and Development Functional Food Centre (CIDAF), Health Science Technological Park, Avenida del Conocimiento 37, BioRegión Building, 18016 Granada, Spain; (I.B.-L.); (J.L.-S.); (A.S.-C.)
- Department of Food Science and Nutrition, University of Granada, Campus of Cartuja, 18071 Granada, Spain
| | - Antonio Segura-Carretero
- Research and Development Functional Food Centre (CIDAF), Health Science Technological Park, Avenida del Conocimiento 37, BioRegión Building, 18016 Granada, Spain; (I.B.-L.); (J.L.-S.); (A.S.-C.)
- Department of Analytical Chemistry, Faculty of Sciences, University of Granada, Avenida Fuentenueva s/n, 18071 Granada, Spain
| | - Vicente Micol
- Instituto de Biología Molecular y Celular (IBMC) and Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universitas Miguel Hernández (UMH), 03202 Elche, Spain; (L.A.-C.); (V.M.); (E.B.-C.)
- CIBER: CB12/03/30038 Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Instituto de Salud Carlos III, 07122 Palma de Mallorca, Spain
| | - María Herranz-López
- Instituto de Biología Molecular y Celular (IBMC) and Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universitas Miguel Hernández (UMH), 03202 Elche, Spain; (L.A.-C.); (V.M.); (E.B.-C.)
- Correspondence: ; Tel.: +34-965222586
| | - Enrique Barrajón-Catalán
- Instituto de Biología Molecular y Celular (IBMC) and Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universitas Miguel Hernández (UMH), 03202 Elche, Spain; (L.A.-C.); (V.M.); (E.B.-C.)
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Silenzi A, Giovannini C, Scazzocchio B, Varì R, D’Archivio M, Santangelo C, Masella R. Extra virgin olive oil polyphenols: biological properties and antioxidant activity. Pathology 2020. [DOI: 10.1016/b978-0-12-815972-9.00022-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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The Potential Synergistic Modulation of AMPK by Lippia citriodora Compounds as a Target in Metabolic Disorders. Nutrients 2019; 11:nu11122961. [PMID: 31817196 PMCID: PMC6950112 DOI: 10.3390/nu11122961] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Revised: 11/26/2019] [Accepted: 11/29/2019] [Indexed: 12/13/2022] Open
Abstract
Lippia citriodora (LC) represents a complex plant-derived source of polyphenols and iridoids that has shown beneficial properties against obesity-related metabolic disorders. The complete extract and its major compound, verbascoside, have shown AMPK-activating capacity in cell and animal models. In this work, we aimed to elucidate the contribution of the different compounds present in the LC extract on the AMPK activation capacity of the whole extract. Semipreparative reversed-phase high-performance liquid chromatography coupled to electrospray ionization time-of-flight mass spectrometry (RP-HPLC-ESI-TOF-MS) was used to identify the major compounds with bioassay-guided fractionation in an adipocyte cell model for the measurement of AMPK activity. Twenty-two compounds were identified and purified almost to homogeneity in 16 fractions, and three compounds, namely verbascoside, luteolin-7-diglucuronide and loganic acid, showed the highest AMPK-activating capacity. The synergy study using the checkerboard and fractional inhibitory concentration index (FICI) methods exhibited synergistic behavior between loganic acid and luteolin-7-diglucuronide. Molecular docking experiments revealed that these three compounds might act as direct agonists of AMPK, binding to the AMP binding sites of the gamma subunit and/or the different sites of the interaction zones between the gamma and beta subunits. Although our findings conclude that the bioactivity of the extract is mainly due to verbascoside, the synergy found between loganic acid and luteolin-7-diglucuronide deserves further research aimed to develop optimized combinations of polyphenols as a new nutritional strategy against obesity-related metabolic disorders.
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11
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Alkhouli M, Laflouf M, Alhaddad M. Evaluation of the effectiveness of olive oil to prevent chemotherapy induced oral mucositis: A randomized controlled clinical trial. PEDIATRIC DENTAL JOURNAL 2019. [DOI: 10.1016/j.pdj.2019.08.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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12
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Curcumin induces multiple signaling pathways leading to vascular smooth muscle cell senescence. Biogerontology 2019; 20:783-798. [PMID: 31372798 PMCID: PMC6790191 DOI: 10.1007/s10522-019-09825-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Accepted: 07/24/2019] [Indexed: 01/01/2023]
Abstract
Curcumin, a phytochemical present in the spice named turmeric, and one of the promising anti-aging factors, is itself able to induce cellular senescence. We have recently shown that cells building the vasculature senesced as a result of curcumin treatment. Curcumin-induced senescence was DNA damage-independent; however, activation of ATM was observed. Moreover, neither increased ROS production, nor even ATM were indispensable for senescence progression. In this paper we tried to elucidate the mechanism of curcumin-induced senescence. We analyzed the time-dependence of the level and activity of numerous proteins involved in senescence progression in vascular smooth muscle cells and how inhibition p38 or p38 together with ATM, two proteins involved in canonical signaling pathways, influenced cell senescence. We showed that curcumin was able to influence many signaling pathways of which probably none was dominant and sufficient to induce senescence by itself. However, we cannot exclude that the switch between initiation and progression of senescence is the result of the impact of curcumin on signaling pathways engaging AMPK, ATM, sirtuin 1 and p300 and on their reciprocal interplay. Cytostatic concentration of curcumin induced cellular stress, which exceeded the adaptive response and, in consequence, led to cellular senescence, which is triggered by time dependent activation of several signaling pathways playing diverse roles in different phases of senescence progression. We also showed that activity of β-glucuronidase, the enzyme involved in deconjugation of the main metabolites of curcumin, glucuronides, increased in senescent cells. It suggests a possible local elevation of curcumin concentration in the organism.
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Francisco V, Ruiz-Fernández C, Lahera V, Lago F, Pino J, Skaltsounis L, González-Gay MA, Mobasheri A, Gómez R, Scotece M, Gualillo O. Natural Molecules for Healthy Lifestyles: Oleocanthal from Extra Virgin Olive Oil. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:3845-3853. [PMID: 30875206 DOI: 10.1021/acs.jafc.8b06723] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Extra virgin olive oil (EVOO) is the main source of fat in the Mediterranean diet. Phenolic compounds of EVOO, in particular, secoiridoids, are minor components that have generated special interest due to their positive effects on human health, supported by several clinical trials. This review summarizes the most recent findings on the pharmacological properties and action's mechanisms of secoiridoid oleocanthal, focusing attention on inflammation, oxidative stress, cancer, neurodegenerative processes, and rheumatic diseases. Being of relevance to the clinical effects of EVOO intake, the bioavailability and biotransformation of EVOO polyphenols are addressed. Moreover, this review summarizes the factors that may influence the oleocanthal concentration in EVOO. With the growing incidence of age- and lifestyle-related diseases, the current data indicated that the administration of EVOO rich in secoiridoids may be helpful in the prevention or treatment of different pathologies with an inflammatory component. Although promising, the future raises several questions and challenges, which are discussed here. The real beneficial effects of olive oil phenols on human health need to be clarified in new, well-designed clinical studies.
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Affiliation(s)
- Vera Francisco
- SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases) , Santiago University Clinical Hospital , Laboratory 9, Building C, Travesía da Choupana S/N , Santiago de Compostela 15706 , Spain
| | - Clara Ruiz-Fernández
- SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases) , Santiago University Clinical Hospital , Laboratory 9, Building C, Travesía da Choupana S/N , Santiago de Compostela 15706 , Spain
| | - Vicente Lahera
- Complutense University , School of Medicine, Department of Physiology , Madrid , Spain
| | - Francisca Lago
- SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), Laboratory of Cellular and Molecular Cardiology , CIBERCV (Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares) , Laboratory 7, Building C, Travesía da Choupana S/N , Santiago de Compostela 15706 , Spain
| | - Jesús Pino
- SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases) , Santiago University Clinical Hospital , Laboratory 9, Building C, Travesía da Choupana S/N , Santiago de Compostela 15706 , Spain
| | - Leandros Skaltsounis
- National and Kapodistrian University of Athens , Faculty of Pharmacy, Department of Pharmacognosy and Natural Products Chemistry , Athens , 15771 , Greece
| | - Miguel Angel González-Gay
- Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL , Santander , 39011 , Spain
| | - Ali Mobasheri
- Department of Regenerative Medicine , State Research Institute Centre for Innovative Medicine , Santariskiu 5 , 08661 Vilnius , Lithuania
| | - Rodolfo Gómez
- SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The Musculoskeletal Pathology Group , Santiago University Clinical Hospital , Laboratory 18, Building C, Travesía da Choupana S/N , Santiago de Compostela 15706 , Spain
| | - Morena Scotece
- SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases) , Santiago University Clinical Hospital , Laboratory 9, Building C, Travesía da Choupana S/N , Santiago de Compostela 15706 , Spain
| | - Oreste Gualillo
- SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases) , Santiago University Clinical Hospital , Laboratory 9, Building C, Travesía da Choupana S/N , Santiago de Compostela 15706 , Spain
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Bielak-Zmijewska A, Grabowska W, Ciolko A, Bojko A, Mosieniak G, Bijoch Ł, Sikora E. The Role of Curcumin in the Modulation of Ageing. Int J Mol Sci 2019; 20:E1239. [PMID: 30871021 PMCID: PMC6429134 DOI: 10.3390/ijms20051239] [Citation(s) in RCA: 82] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Revised: 03/04/2019] [Accepted: 03/06/2019] [Indexed: 12/27/2022] Open
Abstract
It is believed that postponing ageing is more effective and less expensive than the treatment of particular age-related diseases. Compounds which could delay symptoms of ageing, especially natural products present in a daily diet, are intensively studied. One of them is curcumin. It causes the elongation of the lifespan of model organisms, alleviates ageing symptoms and postpones the progression of age-related diseases in which cellular senescence is directly involved. It has been demonstrated that the elimination of senescent cells significantly improves the quality of life of mice. There is a continuous search for compounds, named senolytic drugs, that selectively eliminate senescent cells from organisms. In this paper, we endeavor to review the current knowledge about the anti-ageing role of curcumin and discuss its senolytic potential.
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Affiliation(s)
- Anna Bielak-Zmijewska
- Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-093 Warsaw, Poland.
| | - Wioleta Grabowska
- Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-093 Warsaw, Poland.
| | - Agata Ciolko
- Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-093 Warsaw, Poland.
| | - Agnieszka Bojko
- Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-093 Warsaw, Poland.
| | - Grażyna Mosieniak
- Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-093 Warsaw, Poland.
| | - Łukasz Bijoch
- Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-093 Warsaw, Poland.
| | - Ewa Sikora
- Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-093 Warsaw, Poland.
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Zarrouk A, Martine L, Grégoire S, Nury T, Meddeb W, Camus E, Badreddine A, Durand P, Namsi A, Yammine A, Nasser B, Mejri M, Bretillon L, Mackrill JJ, Cherkaoui-Malki M, Hammami M, Lizard G. Profile of Fatty Acids, Tocopherols, Phytosterols and Polyphenols in Mediterranean Oils (Argan Oils, Olive Oils, Milk Thistle Seed Oils and Nigella Seed Oil) and Evaluation of their Antioxidant and Cytoprotective Activities. Curr Pharm Des 2019; 25:1791-1805. [PMID: 31298157 DOI: 10.2174/1381612825666190705192902] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Accepted: 06/23/2019] [Indexed: 12/30/2022]
Abstract
BACKGROUND The effects of vegetable oils on human health depend on their components. Therefore, their profiles of lipid nutrients and polyphenols were determined. OBJECTIVE To establish and compare the fatty acid, tocopherol, phytosterol and polyphenol profiles of Mediterranean oils: cosmetic and dietary argan oils (AO; Morocco: Agadir, Berkane); olive oils (OO; Morocco, Spain, Tunisia); milk thistle seed oils (MTSO; Tunisia: Bizerte, Sousse, Zaghouane); nigella seed oil (NSO). METHODS The biochemical profiles were determined by gas chromatography-flame ionization, high performance liquid chromatography and gas chromatography, coupled with mass spectrometry as required. The antioxidant and cytoprotective activities were evaluated with the KRL (Kit Radicaux Libres) and the fluorescein diacetate tests on nerve cells treated with 7-ketocholesterol (7KC). RESULTS The fatty acid profile revealed high linoleic acid (C18:2 n-6) content in AO, OO, MTSO and NSO. The highest levels of oleic acid (C18:1 n-9) were found in AO and OO. The tocopherol profile showed that Agadir AO contained the highest amount of α-tocopherol, also present at high level in MTSO and Tunisian OO; Berkane AO was rich in γ-tocopherol. The phytosterol profile indicated that β-sitosterol was predominant in the oils, except AO; spinasterol was only present in AO. Polyphenol profiles underlined that OO was the richest in polyphenols; hydroxytyrosol was only found in OO; few polyphenols were detected in AO. The oils studied have antioxidant activities, and all of them, except NSO, prevented 7KC-induced cell death. The antioxidant characteristics of AO were positively correlated with procatechic acid and compestanol levels. CONCLUSION Based on their biochemical profiles, antioxidant and cytoprotective characteristics, AO, OO, and MTSO are potentially beneficial to human health.
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Affiliation(s)
- Amira Zarrouk
- Laboratoire 'Nutrition, Aliments Fonctionnels et Sante Vasculaire', UR12ES05 Universite de Monastir, Monastir, Tunisia
- Equipe 'Biochimie du Peroxysome, Inflammation et Metabolisme Lipidique' EA 7270 / Universite de Bourgogne Franche-Comte / Inserm, Dijon, France
- Laboratoire de Biochimie, Faculté de Médecine, Sousse, Tunisia
| | - Lucy Martine
- Eye and Nutrition Research Group, Centre des Sciences du Gout et de l'Alimentation, UMR 1324 INRA, 6265 CNRS, Universite de Bourgogne Franche-Comte, Dijon, France
| | - Stéphane Grégoire
- Eye and Nutrition Research Group, Centre des Sciences du Gout et de l'Alimentation, UMR 1324 INRA, 6265 CNRS, Universite de Bourgogne Franche-Comte, Dijon, France
| | - Thomas Nury
- Equipe 'Biochimie du Peroxysome, Inflammation et Metabolisme Lipidique' EA 7270 / Universite de Bourgogne Franche-Comte / Inserm, Dijon, France
| | - Wiem Meddeb
- Institut Superieur de Biotechnologie, Beja, Tunisia
| | | | - Asmaa Badreddine
- Laboratory of 'Biochemistry of Neuroscience', University Hassan 1er, Settat, Morocco
| | | | - Amira Namsi
- Equipe 'Biochimie du Peroxysome, Inflammation et Metabolisme Lipidique' EA 7270 / Universite de Bourgogne Franche-Comte / Inserm, Dijon, France
| | - Aline Yammine
- Equipe 'Biochimie du Peroxysome, Inflammation et Metabolisme Lipidique' EA 7270 / Universite de Bourgogne Franche-Comte / Inserm, Dijon, France
| | - Boubker Nasser
- Laboratory of 'Biochemistry of Neuroscience', University Hassan 1er, Settat, Morocco
| | | | - Lionel Bretillon
- Eye and Nutrition Research Group, Centre des Sciences du Gout et de l'Alimentation, UMR 1324 INRA, 6265 CNRS, Universite de Bourgogne Franche-Comte, Dijon, France
| | - John J Mackrill
- Department of Physiology, BioSciences Institute, Univ. College Cork, Cork, Ireland
| | - Mustapha Cherkaoui-Malki
- Equipe 'Biochimie du Peroxysome, Inflammation et Metabolisme Lipidique' EA 7270 / Universite de Bourgogne Franche-Comte / Inserm, Dijon, France
| | - Mohamed Hammami
- Laboratoire 'Nutrition, Aliments Fonctionnels et Sante Vasculaire', UR12ES05 Universite de Monastir, Monastir, Tunisia
| | - Gérard Lizard
- Equipe 'Biochimie du Peroxysome, Inflammation et Metabolisme Lipidique' EA 7270 / Universite de Bourgogne Franche-Comte / Inserm, Dijon, France
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Serreli G, Deiana M. In vivoformed metabolites of polyphenols and their biological efficacy. Food Funct 2019; 10:6999-7021. [DOI: 10.1039/c9fo01733j] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
The metabolites of polyphenols are antioxidant, anti-inflammatory and anticancer agents. Being bioavailable, they may play an important role in preventing degenerative diseases.
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Affiliation(s)
- Gabriele Serreli
- Department of Biomedical Sciences
- University of Cagliari
- Cagliari
- Italy
| | - Monica Deiana
- Department of Biomedical Sciences
- University of Cagliari
- Cagliari
- Italy
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Biological Relevance of Extra Virgin Olive Oil Polyphenols Metabolites. ANTIOXIDANTS (BASEL, SWITZERLAND) 2018. [PMID: 30469520 DOI: 10.3390/antiox7120170]] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Extra virgin olive oil (EVOO) polyphenols beneficial effects have widely been debated throughout the last three decades, with greater attention to hydroxytyrosol and tyrosol, which are by far the most studied. The main concern about the evaluation of EVOO phenols activities in vitro and in vivo is that the absorption and metabolism of these compounds once ingested lead to the production of different metabolites in the human body. EVOO phenols in the ingested forms are less concentrated in human tissues than their glucuronide, sulfate and methyl metabolites; on the other hand, metabolites may undergo deconjugation before entering the cells and thus act as free forms or may be reformed inside the cells so acting as conjugated forms. In most in vitro studies the presence of methyl/sulfate/glucuronide functional groups does not seem to inhibit biological activity. Parent compounds and metabolites have been shown to reach tissue concentrations useful to exert beneficial effects others than antioxidant and scavenging properties, by modulating intracellular signaling and improving cellular response to oxidative stress and pro-inflammatory stimuli. This review aims to give an overview on the reported evidence of the positive effects exerted by the main EVOO polyphenols metabolites in comparison with the parent compounds.
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Biological Relevance of Extra Virgin Olive Oil Polyphenols Metabolites. Antioxidants (Basel) 2018; 7:antiox7120170. [PMID: 30469520 PMCID: PMC6315336 DOI: 10.3390/antiox7120170] [Citation(s) in RCA: 94] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Revised: 11/19/2018] [Accepted: 11/21/2018] [Indexed: 01/23/2023] Open
Abstract
Extra virgin olive oil (EVOO) polyphenols beneficial effects have widely been debated throughout the last three decades, with greater attention to hydroxytyrosol and tyrosol, which are by far the most studied. The main concern about the evaluation of EVOO phenols activities in vitro and in vivo is that the absorption and metabolism of these compounds once ingested lead to the production of different metabolites in the human body. EVOO phenols in the ingested forms are less concentrated in human tissues than their glucuronide, sulfate and methyl metabolites; on the other hand, metabolites may undergo deconjugation before entering the cells and thus act as free forms or may be reformed inside the cells so acting as conjugated forms. In most in vitro studies the presence of methyl/sulfate/glucuronide functional groups does not seem to inhibit biological activity. Parent compounds and metabolites have been shown to reach tissue concentrations useful to exert beneficial effects others than antioxidant and scavenging properties, by modulating intracellular signaling and improving cellular response to oxidative stress and pro-inflammatory stimuli. This review aims to give an overview on the reported evidence of the positive effects exerted by the main EVOO polyphenols metabolites in comparison with the parent compounds.
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