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Morelli MB, Aguzzi C, Rascioni R, Mignini F. A Study of the Effects of Oleuropein and Polydatin Association on Muscle and Bone Metabolism. Biomolecules 2025; 15:628. [PMID: 40427521 PMCID: PMC12109345 DOI: 10.3390/biom15050628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2025] [Revised: 04/20/2025] [Accepted: 04/23/2025] [Indexed: 05/29/2025] Open
Abstract
Sarcopenia and osteoporosis are age-related musculoskeletal pathologies that often develop in parallel, and numerous studies support the concept of a bone-muscle unit, where deep interaction between the two tissues takes place. In Mediterranean areas, the lowest incidence of osteoporosis within Europe is observed, so the Mediterranean diet was suggested to play an important role. Consequently, in this study, oleuropein, a phenolic compound found in olive oil, and polydatin, another natural polyphenol found in the Mediterranean diet, were evaluated to determine their beneficial effects on bone and muscle metabolism. In human osteoblasts and skeletal muscle myoblasts, the effects were examined, and, after analyzing the cytotoxic effect to find non-toxic doses, the modulation of bone and muscle differentiation markers was evaluated at the gene and protein levels using PCR, Western blot, and immunohistochemistry. Interestingly, the compounds increased markers involved in osteoblast differentiation, such as osteocalcin, type I collagen, and dentin-sialo-phosphoprotein, as well as markers involved in myoblast differentiation, such as myogenic regulatory factors and creatine kinase. These effects were most noticeable when the compounds were administered together. These results suggest a beneficial role for oleuropein-polydatin association on bone and muscle tissue pathologies simultaneously.
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Affiliation(s)
| | - Cristina Aguzzi
- School of Pharmacy, University of Camerino, 62032 Camerino, Italy; (M.B.M.); (C.A.)
| | - Riccardo Rascioni
- International Institute for Clinical Research and Analisys (IICRA srl), Spin Off University of Camerino, 63032 Camerino, Italy;
| | - Fiorenzo Mignini
- International Institute for Clinical Research and Analisys (IICRA srl), Spin Off University of Camerino, 63032 Camerino, Italy;
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Iantomasi M, Terzo M, Tsiani E. Anti-Diabetic Effects of Oleuropein. Metabolites 2024; 14:581. [PMID: 39590817 PMCID: PMC11597061 DOI: 10.3390/metabo14110581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 10/17/2024] [Accepted: 10/25/2024] [Indexed: 11/28/2024] Open
Abstract
Background/Objectives: Oleuropein, a secoiridoid polyphenol found in olive oil as well as the fruit and leaves of the olive tree, has been reported to have antioxidant, cardioprotective, anti-inflammatory, anti-cancer, and anti-diabetic properties. Type 2 diabetes mellitus (TD2M) is a chronic metabolic disease characterized by impaired insulin action, termed insulin resistance. The development of T2DM is closely associated with obesity and chronic low-grade inflammation. In recent years, a rise in sedentary lifestyles and diets rich in refined carbohydrates and saturated fats has contributed to an increase in the prevalence of obesity and TD2M. Currently, the strategies for treating T2DM and its prevention lack efficacy and are associated with adverse side effects. Hence, there is an urgent need for novel treatment strategies, including naturally occurring compounds possessing hypoglycemic and insulin-sensitizing properties. Methods: This review summarizes the evidence of the anti-inflammatory and anti-diabetic properties of oleuropein from in vitro and in vivo animal studies, as well as the available clinical trials. Results: The existing evidence indicates that oleuropein may exert its anti-inflammatory effects by downregulating the levels of pro-inflammatory cytokines in hepatic and adipose tissue. Additionally, the evidence suggests that oleuropein targets skeletal muscle and enhances glucose uptake and its related protein signalling cascades, improving glucose tolerance and insulin sensitivity. Conclusions: Despite the evidence of oleuropein's anti-inflammatory and anti-diabetic potential, more animal and clinical studies are needed to proceed towards its clinical/therapeutic use for metabolic diseases confidently.
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Affiliation(s)
- Michael Iantomasi
- Department of Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada
| | - Matthew Terzo
- Department of Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada
| | - Evangelia Tsiani
- Department of Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada
- Centre for Bone and Muscle Health, Brock University, St. Catharines, ON L2S 3A1, Canada
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Balbuena-Pecino S, Montblanch M, Rosell-Moll E, González-Fernández V, García-Meilán I, Fontanillas R, Gallardo Á, Gutiérrez J, Capilla E, Navarro I. Impact of Hydroxytyrosol-Rich Extract Supplementation in a High-Fat Diet on Gilthead Sea Bream ( Sparus aurata) Lipid Metabolism. Antioxidants (Basel) 2024; 13:403. [PMID: 38671851 PMCID: PMC11047642 DOI: 10.3390/antiox13040403] [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: 02/26/2024] [Revised: 03/19/2024] [Accepted: 03/25/2024] [Indexed: 04/28/2024] Open
Abstract
High-fat diets (HFDs) enhance fish growth by optimizing nutrient utilization (i.e., protein-sparing effect); however, their potential negative effects have also encouraged the search for feed additives. This work has investigated the effects of an extract rich in a polyphenolic antioxidant, hydroxytyrosol (HT), supplemented (0.52 g HT/kg feed) in a HFD (24% lipid) in gilthead sea bream (Sparus aurata). Fish received the diet at two ration levels, standard (3% of total fish weight) or restricted (40% reduction) for 8 weeks. Animals fed the supplemented diet at a standard ration had the lowest levels of plasma free fatty acids (4.28 ± 0.23 mg/dL versus 6.42 ± 0.47 in the non-supplemented group) and downregulated hepatic mRNA levels of lipid metabolism markers (ppara, pparb, lpl, fatp1, fabp1, acox1, lipe and lipa), supporting potential fat-lowering properties of this compound in the liver. Moreover, the same animals showed increased muscle lipid content and peroxidation (1.58- and 1.22-fold, respectively, compared to the fish without HT), suggesting the modulation of body adiposity distribution and an enhanced lipid oxidation rate in that tissue. Our findings emphasize the importance of considering this phytocompound as an optimal additive in HFDs for gilthead sea bream to improve overall fish health and condition.
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Affiliation(s)
- Sara Balbuena-Pecino
- Departament de Biologia Cellular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain; (S.B.-P.); (M.M.); (E.R.-M.); (V.G.-F.); (I.G.-M.); (Á.G.); (J.G.); (E.C.)
| | - Manel Montblanch
- Departament de Biologia Cellular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain; (S.B.-P.); (M.M.); (E.R.-M.); (V.G.-F.); (I.G.-M.); (Á.G.); (J.G.); (E.C.)
| | - Enrique Rosell-Moll
- Departament de Biologia Cellular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain; (S.B.-P.); (M.M.); (E.R.-M.); (V.G.-F.); (I.G.-M.); (Á.G.); (J.G.); (E.C.)
| | - Verónica González-Fernández
- Departament de Biologia Cellular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain; (S.B.-P.); (M.M.); (E.R.-M.); (V.G.-F.); (I.G.-M.); (Á.G.); (J.G.); (E.C.)
| | - Irene García-Meilán
- Departament de Biologia Cellular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain; (S.B.-P.); (M.M.); (E.R.-M.); (V.G.-F.); (I.G.-M.); (Á.G.); (J.G.); (E.C.)
| | | | - Ángeles Gallardo
- Departament de Biologia Cellular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain; (S.B.-P.); (M.M.); (E.R.-M.); (V.G.-F.); (I.G.-M.); (Á.G.); (J.G.); (E.C.)
| | - Joaquim Gutiérrez
- Departament de Biologia Cellular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain; (S.B.-P.); (M.M.); (E.R.-M.); (V.G.-F.); (I.G.-M.); (Á.G.); (J.G.); (E.C.)
| | - Encarnación Capilla
- Departament de Biologia Cellular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain; (S.B.-P.); (M.M.); (E.R.-M.); (V.G.-F.); (I.G.-M.); (Á.G.); (J.G.); (E.C.)
| | - Isabel Navarro
- Departament de Biologia Cellular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain; (S.B.-P.); (M.M.); (E.R.-M.); (V.G.-F.); (I.G.-M.); (Á.G.); (J.G.); (E.C.)
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Gómez G, Laviano HD, García-Casco J, Muñoz M, Gómez F, Sánchez-Esquiliche F, González-Bulnes A, López-Bote C, Óvilo C, Rey AI. Long-Term Effect of Maternal Antioxidant Supplementation on the Lipid Profile of the Progeny According to the Sow's Parity Number. Antioxidants (Basel) 2024; 13:379. [PMID: 38539912 PMCID: PMC10968619 DOI: 10.3390/antiox13030379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 03/13/2024] [Accepted: 03/18/2024] [Indexed: 08/30/2024] Open
Abstract
Pig feeding prior to the extensive fattening phase might affect the final lipid profile and product quality. This study evaluates how maternal supplementation with vitamin E (VITE) (100 mg/kg), hydroxytyrosol (HXT) (1.5 mg/kg), or combined administration (VE + HXT) affects the piglet's plasma and tissues' fatty acid profiles and lipid stability according to the sow's parity number (PN), as well as the possible changes to the lipid profile after extensive feeding. The sows' PN affected the total fatty acid profile of plasma, muscle, and liver of piglets, with lower Δ-9 and Δ-6 desaturase indices but higher Δ-5 in those from primiparous (P) than multiparous (M) sows. Dietary VITE was more effective at decreasing C16:0 and saturated fatty acids in the muscle of piglets born from M than P sows, and modified the liver phospholipids in a different way. Sows' supplementation with HXT increased C18:2n-6 in triglycerides and polyunsaturated fatty acids (PUFA) in muscle phospholipids. In the liver, HXT supplementation also increased free-PUFA and free-n-3 fatty acids. However, lipid oxidation of piglets' tissues was not affected by the antioxidant supplementation, and it was higher in the livers of piglets born from M sows. The fatty acid profile in the muscle of pigs after extensive feeding was not affected by the PN, but it was by the sows' antioxidant supplementation, with positive effects on quality by both compounds.
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Affiliation(s)
- Gerardo Gómez
- Instituto Regional de Investigación y Desarrollo Agroalimentario y Forestal de Castilla-La Mancha (IRIAF), 13700 Toledo, Spain;
| | - Hernan D. Laviano
- Departamento Producción Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Avda. Puerta de Hierro s/n., 28040 Madrid, Spain
| | - Juan García-Casco
- Departamento de Mejora Genética Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Consejo Superior de Investigaciones Científicas (CSIC), Ctra Coruña km 7.5, 28040 Madrid, Spain
| | - Maria Muñoz
- Departamento de Mejora Genética Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Consejo Superior de Investigaciones Científicas (CSIC), Ctra Coruña km 7.5, 28040 Madrid, Spain
| | - Fernando Gómez
- Sánchez Romero Carvajal, Carretera de San Juan del Puerto, s/n, 21290 Jabugo, Spain
| | | | - Antonio González-Bulnes
- Departamento de Producción y Sanidad Animal, Facultad de Veterinaria, Universidad Cardenal Herrera-CEU, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain
| | - Clemente López-Bote
- Departamento Producción Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Avda. Puerta de Hierro s/n., 28040 Madrid, Spain
| | - Cristina Óvilo
- Departamento de Mejora Genética Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Consejo Superior de Investigaciones Científicas (CSIC), Ctra Coruña km 7.5, 28040 Madrid, Spain
| | - Ana I. Rey
- Departamento Producción Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Avda. Puerta de Hierro s/n., 28040 Madrid, Spain
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Basheer M, Boulos M, Basheer A, Loai A, Nimer A. Olive Oil's Attenuating Effects on Lipotoxicity. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1460:869-882. [PMID: 39287875 DOI: 10.1007/978-3-031-63657-8_29] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]
Abstract
Dietary fatty acids play a role in the pathogenesis of obesity-associated nonalcoholic fatty liver disease. Lipotoxicity in obesity mediates insulin resistance, endothelial dysfunction, atherosclerosis, and gut microbiota dysbiosis. Cardiovascular complications are the main cause of morbidity and mortality in obese, insulin-resistant, and type 2 diabetes mellitus patients.Interventions targeting lipotoxicity are the main issue in preventing its multiple insults. Lifestyle modifications including healthy eating and regular exercise are the primary recommendations. Treatments also include drugs targeting energy intake, energy disposal, lipotoxic liver injury, and the resulting inflammation, fibrogenesis, and cirrhosis.Diet and nutrition have been linked to insulin resistance, an increased risk of developing type 2 diabetes, and impaired postprandial lipid metabolism. Low-fat diets are associated with higher survival. The Mediterranean diet includes an abundance of olive oil. Extra-virgin olive oil is the main source of monounsaturated fatty acids in Mediterranean diets. An olive oil-rich diet decreases triglyceride accumulation in the liver, improves postprandial triglyceride levels, improves glucose and insulin secretions, and upregulates GLUT-2 expression in the liver. The exact molecular mechanisms of olive oil's effects are unknown, but decreasing NF-kB activation, decreasing LDL oxidation, and improving insulin resistance by reducing the production of inflammatory cytokines (TNF-α and IL-6) and upregulating kinases and JNK-mediated phosphorylation of IRS-1 are possible principal mechanisms. Olive oil phenolic compounds also modulate gut microbiota diversity, which also affects lipotoxicity.In this review, we document lipotoxicity in obesity manifestations and the beneficial health effects of the Mediterranean diet derived from monounsaturated fatty acids, mainly from olive oil.
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Affiliation(s)
- Maamoun Basheer
- Department of Internal Medicine A, Galilee Medical Center, Nahariya, Israel
| | - Mariana Boulos
- Department of Internal Medicine A, Galilee Medical Center, Nahariya, Israel
| | - Areej Basheer
- Department of Internal Medicine A, Galilee Medical Center, Nahariya, Israel
- Nutrition and Diet Services, Hillel Yaffe, Hadera, Israel
| | - Arraf Loai
- Department of Internal Medicine A, Galilee Medical Center, Nahariya, Israel
| | - Assy Nimer
- Department of Internal Medicine A, Galilee Medical Center, Nahariya, Israel.
- Faculty of Medicine at Galilee, Bar-Ilan University, Safed, Israel.
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Wang R, Ganbold M, Ferdousi F, Tominaga K, Isoda H. A Rare Olive Compound Oleacein Improves Lipid and Glucose Metabolism, and Inflammatory Functions: A Comprehensive Whole-Genome Transcriptomics Analysis in Adipocytes Differentiated from Healthy and Diabetic Adipose Stem Cells. Int J Mol Sci 2023; 24:10419. [PMID: 37445596 DOI: 10.3390/ijms241310419] [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: 05/24/2023] [Revised: 06/12/2023] [Accepted: 06/18/2023] [Indexed: 07/15/2023] Open
Abstract
Oleacein (OLE), a rare natural compound found in unfiltered extra virgin olive oil, has been shown to have anti-inflammatory and anti-obesity properties. However, little is known regarding the mechanisms by which OLE influences metabolic processes linked to disease targets, particularly in the context of lipid metabolism. In the present study, we conducted whole-genome DNA microarray analyses in adipocytes differentiated from human adipose-derived stem cells (hASCs) and diabetic hASCs (d-hASCs) to examine the effects of OLE on modulating metabolic pathways. We found that OLE significantly inhibited lipid formation in adipocytes differentiated from both sources. In addition, microarray analysis demonstrated that OLE treatment could significantly downregulate lipid-metabolism-related genes and modulate glucose metabolism in both adipocyte groups. Transcription factor enrichment and protein-protein interaction (PPI) analyses identified potential regulatory gene targets. We also found that OLE treatment enhanced the anti-inflammatory properties in adipocytes. Our study findings suggest that OLE exhibits potential benefits in improving lipid and glucose metabolism, thus holding promise for its application in the management of metabolic disorders.
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Affiliation(s)
- Rui Wang
- Tsukuba Life Science Innovation Program (T-LSI), University of Tsukuba, Tsukuba 305-8577, Japan
| | - Munkhzul Ganbold
- Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8577, Japan
| | - Farhana Ferdousi
- Tsukuba Life Science Innovation Program (T-LSI), University of Tsukuba, Tsukuba 305-8577, Japan
- Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba 305-8577, Japan
- Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan
| | - Kenichi Tominaga
- Tsukuba Life Science Innovation Program (T-LSI), University of Tsukuba, Tsukuba 305-8577, Japan
- Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8577, Japan
| | - Hiroko Isoda
- Tsukuba Life Science Innovation Program (T-LSI), University of Tsukuba, Tsukuba 305-8577, Japan
- Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8577, Japan
- Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba 305-8577, Japan
- Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan
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Khalil AA, Rahman MM, Rauf A, Islam MR, Manna SJ, Khan AA, Ullah S, Akhtar MN, Aljohani ASM, Abdulmonem WA, Simal-Gandara J. Oleuropein: Chemistry, extraction techniques and nutraceutical perspectives-An update. Crit Rev Food Sci Nutr 2023; 64:9933-9954. [PMID: 37272499 DOI: 10.1080/10408398.2023.2218495] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Olive family (Oleaceae) contains several species among which Olea europaea L. is mostly used for production of olive oils. Various parts of olive tree are rich source of diverse bioactive compounds such as Apigenin, elenolic acid, Hydroxytyrosol, Ligstroside, Oleoside, Oleuropein, Oleuropein aglycone, Tyrosol, etc. Among these, oleuropein, a secoiridoid is predominantly found in olive leaves and young olive fruits of different species of Oleaceae family. Scientists have adopted numerous extraction methods (conventional & latest) to increase the yield of oleuropein. Among these techniques, maceration, soxhlet, microwave-assisted, ultrasonication, and supercritical fluid methods are most commonly employed for extraction of oleuropein. Evidently, this review emphasizes on various in-vitro and in-vivo studies focusing on nutraceutical properties of oleuropein. Available literature highlights the pharmaceutical potential of oleuropein against various diseases such as obesity, diabetes, cardiovascular complications, neurodegenerative diseases, cancer, inflammation, microbial infections, and oxidation. This review will benefit the scientific community as it narrates comprehensive literature regarding absorption, metabolism, bioavailability, extraction techniques, and nutraceutical perspectives associated with oleuropein.
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Affiliation(s)
- Anees Ahmed Khalil
- University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan
| | - Md Mominur Rahman
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Anbar, Khyber Pakhtunkhwa, Pakistan
| | - Md Rezaul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Sultana Juhara Manna
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Ammar Ahmed Khan
- University Institute of Food Science and Technology, Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan
| | - Samee Ullah
- University Institute of Food Science and Technology, Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan
| | - Muhammad Nadeem Akhtar
- University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan
| | - Abdullah S M Aljohani
- Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, Qassim University, Saudi Arabia
| | - Waleed Al Abdulmonem
- Department of Pathology, College of Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Jesus Simal-Gandara
- Department of Analytical Chemistry and Food Science, Faculty of Science, Universidade de Vigo, Nutrition and Bromatology Group, Ourense, Spain
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Huang S, Qi B, Yang L, Wang X, Huang J, Zhao Y, Hu Y, Xiao W. Phytoestrogens, novel dietary supplements for breast cancer. Biomed Pharmacother 2023; 160:114341. [PMID: 36753952 DOI: 10.1016/j.biopha.2023.114341] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 01/26/2023] [Accepted: 01/27/2023] [Indexed: 02/08/2023] Open
Abstract
While endocrine therapy is considered as an effective way to treat breast cancer, it still faces many challenges, such as drug resistance and individual discrepancy. Therefore, novel preventive and therapeutic modalities are still in great demand to decrease the incidence and mortality rate of breast cancer. Numerous studies suggested that G protein-coupled estrogen receptor (GPER), a membrane estrogen receptor, is a potential target for breast cancer prevention and treatment. It was also shown that not only endogenous estrogens can activate GPERs, but many phytoestrogens can also function as selective estrogen receptor modulators (SERMs) to interact GPERs. In this review, we discussed the possible mechanisms of GPERs pathways and shed a light of developing novel phytoestrogens based dietary supplements against breast cancers.
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Affiliation(s)
- Shuo Huang
- School of Clinical Medicine, Chengdu University of TCM, Chengdu 610072, Sichuan, China
| | - Baowen Qi
- South China Hospital of Shenzhen University, No. 1, Fuxin Road, Longgang District, Shenzhen, 518116, P. R. China; BioCangia Inc., 205 Torbay Road, Markham, ON L3R 3W4, Canada
| | - Ling Yang
- School of Clinical Medicine, Chengdu University of TCM, Chengdu 610072, Sichuan, China
| | - Xue Wang
- School of Clinical Medicine, Chengdu University of TCM, Chengdu 610072, Sichuan, China
| | - Jing Huang
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China
| | - Ya Zhao
- School of Clinical Medicine, Chengdu University of TCM, Chengdu 610072, Sichuan, China
| | - Yonghe Hu
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China; Department of Pharmacy, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan, China.
| | - Wenjing Xiao
- Department of Pharmacy, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan, China.
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9
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The Oleoside-type Secoiridoid Glycosides: Potential Secoiridoids with Multiple Pharmacological Activities. J Mol Struct 2023. [DOI: 10.1016/j.molstruc.2023.135286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]
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10
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Olive Leaves Extract and Oleuropein Improve Insulin Sensitivity in 3T3-L1 Cells and in High-Fat Diet-Treated Rats via PI3K/AkT Signaling Pathway. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2023; 2023:6828230. [PMID: 36647430 PMCID: PMC9840553 DOI: 10.1155/2023/6828230] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 12/04/2022] [Accepted: 12/12/2022] [Indexed: 01/09/2023]
Abstract
Olive leaves extracts are known to exert potential pharmacological activities especially, antidiabetic and antiobesity. This study explores the anti-insulin resistant effect of olive leaves extracts and oleuropein in 3 T3-L1 cells and in high-fat diet fed rats. Our results showed that ethanol extract (EE) suppressed significantly (P < 0.01) triacylglycerol accumulation. In preadipocytes cells, EE 1/100 decreased cell viability and induced apoptosis. Real-time PCR analysis showed that EE reduced the mRNA levels of adipogenesis (CEBP-α, PPARγ, SREBP-1c, and FAS) and proinflammatory (TNF-α and IL-6) genes. Moreover, the cotreatment of EE 1/1000 or oleuropein with insulin increased considerably the expression of p-IRS, p85-pI3K, and p-AKT. In vivo model, the oral administration of oleuropein at 50 mg/kg in rats fed with high fat diet for 8 weeks reduced inflammation in liver and adipose tissues (WAT), improved glucose intolerance, and decreased hyperinsulinemia. Furthermore, the immunohistochemistry revealed that the expression level of p-Akt, IRS1, and Glut-4 were significantly enhanced in liver and WAT tissues after oleuropein supplementation comparing with that in HFD group. Additionally, the expression of IRS1 was markedly ameliorated in pancreas. Our obtained results can be adopted as an approach to used olive leaves as complement to prevent insulin-resistance disease.
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11
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Lao A, Chen Y, Sun Y, Wang T, Lin K, Liu J, Wu J. Transcriptomic analysis provides a new insight: Oleuropein reverses high glucose-induced osteogenic inhibition in bone marrow mesenchymal stem cells via Wnt10b activation. Front Bioeng Biotechnol 2022; 10:990507. [PMID: 36091442 PMCID: PMC9459378 DOI: 10.3389/fbioe.2022.990507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Accepted: 07/27/2022] [Indexed: 11/17/2022] Open
Abstract
Adverse events of diabetes mellitus (DM) include bone damages, such as the increased incidence of osteoporosis and bone fractures, which are known as diabetic osteopathy. The pathogenic mechanism of diabetic osteopathy is complex, and hyperglycemia is a vital cause involved in it. Bone marrow mesenchymal stem cells (BMSCs) exert a significant effect on bone formation. Therefore, in this paper, transcriptomic changes of BMSCs cultured in high glucose (35 mM) for 30 days are mainly investigated. In addition, 794 up-regulated genes and 1,162 down-regulated genes were identified. Then, biological functions of the differentially expressed genes in the high glucose microenvironment were investigated by two kinds of functional analyses. Gene Set Enrichment Analysis was also applied to focus on the significant gene sets and it is found that Wnt10b expression witnessed a remarkable decrease in BMSCs under the high glucose microenvironment. At last, in vitro experiments revealed that oleuropein effectively reversed high glucose-induced osteogenic inhibition via activating Wnt10b in BMSCs.
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Affiliation(s)
- An Lao
- Department of Stomatology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yu Chen
- Shanghai Key Laboratory of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Oral and Cranio-maxillofacial Surgery, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Yiting Sun
- Shanghai Key Laboratory of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Oral and Cranio-maxillofacial Surgery, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Tiange Wang
- Shanghai Key Laboratory of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Oral and Cranio-maxillofacial Surgery, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Kaili Lin
- Shanghai Key Laboratory of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Oral and Cranio-maxillofacial Surgery, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China
- *Correspondence: Kaili Lin, ; Jiaqiang Liu, ; Jianyong Wu,
| | - Jiaqiang Liu
- Shanghai Key Laboratory of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Oral and Cranio-maxillofacial Surgery, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China
- *Correspondence: Kaili Lin, ; Jiaqiang Liu, ; Jianyong Wu,
| | - Jianyong Wu
- Department of Stomatology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- *Correspondence: Kaili Lin, ; Jiaqiang Liu, ; Jianyong Wu,
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12
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Jiménez-Sánchez A, Martínez-Ortega AJ, Remón-Ruiz PJ, Piñar-Gutiérrez A, Pereira-Cunill JL, García-Luna PP. Therapeutic Properties and Use of Extra Virgin Olive Oil in Clinical Nutrition: A Narrative Review and Literature Update. Nutrients 2022; 14:nu14071440. [PMID: 35406067 PMCID: PMC9003415 DOI: 10.3390/nu14071440] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 03/24/2022] [Accepted: 03/25/2022] [Indexed: 02/06/2023] Open
Abstract
Extra virgin olive oil (EVOO) is a cornerstone of the Mediterranean diet (MedD). In this narrative review, we synthesize and illustrate the various characteristics and clinical applications of EVOO and its components—such as oleic acid, hydroxytyrosol, and oleuropein—in the field of clinical nutrition and dietetics. The evidence is split into diet therapy, oleic acid-based enteral nutrition formulations and oral supplementation formulations, oleic acid-based parenteral nutrition, and nutraceutical supplementation of minor components of EVOO. EVOO has diverse beneficial health properties, and current evidence supports the use of whole EVOO in diet therapy and the supplementation of its minor components to improve cardiovascular health, lipoprotein metabolism, and diabetes mellitus in clinical nutrition. Nevertheless, more intervention studies in humans are needed to chisel specific recommendations for its therapeutic use through different formulations in other specific diseases and clinical populations.
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Affiliation(s)
- Andrés Jiménez-Sánchez
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Seville, Spain; (P.J.R.-R.); (A.P.-G.); (J.L.P.-C.)
- Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Avda. Manuel Siurot s/n, 41013 Seville, Spain;
- Correspondence: (A.J.-S.); (P.P.G.-L.)
| | - Antonio Jesús Martínez-Ortega
- Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Avda. Manuel Siurot s/n, 41013 Seville, Spain;
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Torrecárdenas, C. Hermandad de Donantes de Sangre, s/n, 04009 Almería, Spain
| | - Pablo Jesús Remón-Ruiz
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Seville, Spain; (P.J.R.-R.); (A.P.-G.); (J.L.P.-C.)
- Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Avda. Manuel Siurot s/n, 41013 Seville, Spain;
| | - Ana Piñar-Gutiérrez
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Seville, Spain; (P.J.R.-R.); (A.P.-G.); (J.L.P.-C.)
- Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Avda. Manuel Siurot s/n, 41013 Seville, Spain;
| | - José Luis Pereira-Cunill
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Seville, Spain; (P.J.R.-R.); (A.P.-G.); (J.L.P.-C.)
- Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Avda. Manuel Siurot s/n, 41013 Seville, Spain;
| | - Pedro Pablo García-Luna
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Seville, Spain; (P.J.R.-R.); (A.P.-G.); (J.L.P.-C.)
- Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Avda. Manuel Siurot s/n, 41013 Seville, Spain;
- Correspondence: (A.J.-S.); (P.P.G.-L.)
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13
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Da Porto A, Brosolo G, Casarsa V, Bulfone L, Scandolin L, Catena C, Sechi LA. The Pivotal Role of Oleuropein in the Anti-Diabetic Action of the Mediterranean Diet: A Concise Review. Pharmaceutics 2021; 14:pharmaceutics14010040. [PMID: 35056936 PMCID: PMC8778910 DOI: 10.3390/pharmaceutics14010040] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 12/17/2021] [Accepted: 12/21/2021] [Indexed: 01/04/2023] Open
Abstract
Type 2 diabetes currently accounts for more than 90% of all diabetic patients. Lifestyle interventions and notably dietary modifications are one of the mainstays for the prevention and treatment of type 2 diabetes. In this context, the Mediterranean diet with its elevated content of phytonutrients has been demonstrated to effectively improve glucose homeostasis. Oleuropein is the most abundant polyphenolic compound contained in extra-virgin olive oil and might account for some of the anti-diabetic actions of the Mediterranean diet. With the aim to provide an overview of the possible contributions of oleuropein to glucose metabolism, we conducted a PubMed/Medline search in order to provide an update to the available evidence regarding this interesting compound. This narrative review summarizes the data that was obtained in in vitro and animal studies and the results of clinical investigations. Preclinical studies indicate that oleuropein improves glucose transport, increases insulin sensitivity, and facilitates insulin secretion by pancreatic β-cells, thereby supporting the hypothesis of the possible benefits of the control of hyperglycemia. However, on the clinical side, the available evidence is still preliminary and requires more extensive investigations. Thus, many questions remain unanswered in regards to the potential benefits of oleuropein in diabetes prevention and treatment. These questions should be addressed in appropriately designed studies in the future.
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14
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Hadrich F, Chamkha M, Sayadi S. Protective effect of olive leaves phenolic compounds against neurodegenerative disorders: Promising alternative for Alzheimer and Parkinson diseases modulation. Food Chem Toxicol 2021; 159:112752. [PMID: 34871668 DOI: 10.1016/j.fct.2021.112752] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 11/24/2021] [Accepted: 12/01/2021] [Indexed: 02/07/2023]
Abstract
The main objective of this work was to review literature on compounds extracted from olive tree leaves, such as simple phenols (hydroxytyrosol) and flavonoids (Apigenin, apigenin-7-O-glucoside, luteolin.) and their diverse pharmacological activities as antioxidant, antimicrobial, anti-viral, anti-obesity, anti-inflammatory and neuroprotective properties. In addition, the study discussed the key mechanisms underlying their neuroprotective effects. This study adopted an approach of collecting data through the databases provided by ScienceDirect, SCOPUS, MEDLINE, PubMed and Google Scholar. This review revealed that there was an agreement on the great impact of olive tree leaves phenolic compounds on many metabolic syndromes as well as on the most prevalent neurodegenerative diseases such as Alzheimer and Parkinson. These findings would be of great importance for the use of olive tree leaves extracts as a food supplement and/or a source of drugs for many diseases. In addition, this review would of great help to beginning researchers in the field since it would offer them a general overview of the studies undertaken in the last two decades on the topic.
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Affiliation(s)
- Fatma Hadrich
- Environmental Bioprocesses Laboratory, Center of Biotechnology of Sfax, P.O. Box 1177, 3038, Sfax, Tunisia.
| | - Mohamed Chamkha
- Environmental Bioprocesses Laboratory, Center of Biotechnology of Sfax, P.O. Box 1177, 3038, Sfax, Tunisia
| | - Sami Sayadi
- Biotechnology Program, Center of Sustainable Development, College of Arts and Sciences, Qatar University, Doha, 2713, Qatar.
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15
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Haidari F, Shayesteh F, Mohammad-Shahi M, Jalali MT, Ahmadi-Angali K. Olive Leaf Extract Supplementation Combined with Calorie-Restricted Diet on Reducing Body Weight and Fat Mass in Obese Women: Result of a Randomized Control Trial. Clin Nutr Res 2021; 10:314-329. [PMID: 34796136 PMCID: PMC8575641 DOI: 10.7762/cnr.2021.10.4.314] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 10/13/2021] [Accepted: 10/14/2021] [Indexed: 12/15/2022] Open
Abstract
The present trial aims to evaluate a supplementation of the olive leaf extract (OLE) in adjunct with a weight loss diet on anthropometric indices, glycemic indices, lipid profile, as well as the level of adipokines, and free fatty acid in obese women. We carried out an 8-week randomized, placebo-controlled, double-blind, parallel-group, clinical trial. The participants were randomly stratified according to age and they were assigned to one of the two study groups: Standard weight loss diet (estimated daily energy requirements minus 500 kcal) + OLE supplementation (n = 35) in intervention group or Standard weight loss diet (estimated daily energy requirements minus 500 kcal) + placebo (n = 35) in placebo group. The study groups were homogeneous regarding the baseline age, height, weight, body mass index (BMI), waist circumferences, married status, and physical activity levels (p > 0.05). The results of analysis of covariance presented significant decreases in BMI, fat mass, and body weight in the OLE group compared to those in the placebo group (p < 0.05). At the end of the study, the serum levels of fasting blood sugar, insulin, low-density lipoprotein cholesterol, total cholesterol, leptin, fatty free acid, and homeostasis model assessment–insulin resistance significantly decreased, and serum levels of high-density lipoprotein cholesterol and adiponectin elevated in the intervention group (p < 0.05). Based on results it seems that the addition of OLE to a hypocaloric diet for 8-week compared with a hypocaloric diet alone may be more effective in modifying obesity and metabolic risk factors.
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Affiliation(s)
- Fatemeh Haidari
- Department of Nutrition, Faculty of Paramedical Sciences, Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical sciences, Ahvaz 61357-15794, Iran
| | - Forough Shayesteh
- Department of Nutrition, Faculty of Paramedical Sciences, Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical sciences, Ahvaz 61357-15794, Iran.,Diabetes Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 5794-61357, Iran
| | - Majid Mohammad-Shahi
- Department of Nutrition, Faculty of Paramedical Sciences, Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical sciences, Ahvaz 61357-15794, Iran
| | - Mohammad-Taha Jalali
- Hyperlipidemia Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 5794-61357, Iran
| | - Kambiz Ahmadi-Angali
- Faculty of Public Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 5794-61357, Iran
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16
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Borah AK, Sharma P, Singh A, Kalita KJ, Saha S, Chandra Borah J. Adipose and non-adipose perspectives of plant derived natural compounds for mitigation of obesity. JOURNAL OF ETHNOPHARMACOLOGY 2021; 280:114410. [PMID: 34273447 DOI: 10.1016/j.jep.2021.114410] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 07/07/2021] [Accepted: 07/10/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Phyto-preparations and phyto-compounds, by their natural origin, easy availability, cost-effectiveness, and fruitful traditional uses based on accumulated experiences, have been extensively explored to mitigate the global burden of obesity. AIM OF THIS REVIEW The review aimed to analyse and critically summarize the prospect of future anti-obesity drug leads from the extant array of phytochemicals for mitigation of obesity, using adipose related targets (adipocyte formation, lipid metabolism, and thermogenesis) and non-adipose targets (hepatic lipid metabolism, appetite, satiety, and pancreatic lipase activity). Phytochemicals as inhibitors of adipocyte differentiation, modulators of lipid metabolism, and thermogenic activators of adipocytes are specifically discussed with their non-adipose anti-obesogenic targets. MATERIALS AND METHODS PubMed, Google Scholar, Scopus, and SciFinder were accessed to collect data on traditional medicinal plants, compounds derived from plants, their reported anti-obesity mechanisms, and therapeutic targets. The taxonomically accepted name of each plant in this review has been vetted from "The Plant List" (www.theplantlist.org) or MPNS (http://mpns.kew.org). RESULTS Available knowledge of a large number of phytochemicals, across a range of adipose and non-adipose targets, has been critically analysed and delineated by graphical and tabular depictions, towards mitigation of obesity. Neuro-endocrinal modulation in non-adipose targets brought into sharp dual focus, both non-adipose and adipose targets as the future of anti-obesity research. Numerous phytochemicals (Berberine, Xanthohumol, Ursolic acid, Guggulsterone, Tannic acid, etc.) have been found to be effectively reducing weight through lowered adipocyte formation, increased lipolysis, decreased lipogenesis, and enhanced thermogenesis. They have been affirmed as potential anti-obesity drugs of future because of their effectiveness yet having no threat to adipose or systemic insulin sensitivity. CONCLUSION Due to high molecular diversity and a greater ratio of benefit to risk, plant derived compounds hold high therapeutic potential to tackle obesity and associated risks. This review has been able to generate fresh perspectives on the anti-diabetic/anti-hyperglycemic/anti-obesity effect of phytochemicals. It has also brought into the focus that many phytochemicals demonstrating in vitro anti-obesogenic effects are yet to undergo in vivo investigation which could lead to potential phyto-molecules for dedicated anti-obesity action.
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Affiliation(s)
- Anuj Kumar Borah
- Dept. of Molecular Biology and Biotechnology, Tezpur University, Napaam, Tezpur, 784028, Assam, India
| | - Pranamika Sharma
- Laboratory of Chemical Biology, Life Sciences Division, Institute of Advanced Study in Science & Technology, Guwahati, 781035, Assam, India
| | - Archana Singh
- Dept. of Molecular Biology and Biotechnology, Tezpur University, Napaam, Tezpur, 784028, Assam, India
| | - Kangkan Jyoti Kalita
- Laboratory of Chemical Biology, Life Sciences Division, Institute of Advanced Study in Science & Technology, Guwahati, 781035, Assam, India
| | - Sougata Saha
- Dept. of Biotechnology, NIT Durgapur, West Bengal, 713209, India
| | - Jagat Chandra Borah
- Laboratory of Chemical Biology, Life Sciences Division, Institute of Advanced Study in Science & Technology, Guwahati, 781035, Assam, India.
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17
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Madureira J, Margaça FMA, Santos-Buelga C, Ferreira ICFR, Verde SC, Barros L. Applications of bioactive compounds extracted from olive industry wastes: A review. Compr Rev Food Sci Food Saf 2021; 21:453-476. [PMID: 34773427 DOI: 10.1111/1541-4337.12861] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 09/20/2021] [Accepted: 09/23/2021] [Indexed: 11/28/2022]
Abstract
The wastes generated during the olive oil extraction process, even if presenting a negative impact for the environment, contain several bioactive compounds that have considerable health benefits. After suitable extraction and purification, these compounds can be used as food antioxidants or as active ingredients in nutraceutical and cosmetic products due to their interesting technological and pharmaceutical properties. The aim of this review, after presenting general applications of the different types of wastes generated from this industry, is to focus on the olive pomace produced by the two-phase system and to explore the challenging applications of the main individual compounds present in this waste. Hydroxytyrosol, tyrosol, oleuropein, oleuropein aglycone, and verbascoside are the most abundant bioactive compounds present in olive pomace. Besides their antioxidant activity, these compounds also demonstrated other biological properties such as antimicrobial, anticancer, or anti-inflammatory, thus being used in formulations to produce pharmaceutical and cosmetic products or in the fortification of food. Nevertheless, it is mandatory to involve both industries and researchers to create strategies to valorize these byproducts while maintaining environmental sustainability.
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Affiliation(s)
- Joana Madureira
- Centro de Ciências e Tecnologias Nucleares (C2TN), Instituto Superior Técnico, Universidade de Lisboa, Loures, Portugal.,Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, Bragança, Portugal.,Grupo de Investigación en Polifenoles (GIP-USAL), Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno s /n, Salamanca, Spain
| | - Fernanda M A Margaça
- Centro de Ciências e Tecnologias Nucleares (C2TN), Instituto Superior Técnico, Universidade de Lisboa, Loures, Portugal
| | - Celestino Santos-Buelga
- Grupo de Investigación en Polifenoles (GIP-USAL), Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno s /n, Salamanca, Spain.,Unidad de Excelencia Producción, Agrícola y Medioambiente (AGRIENVIRONMENT), Parque Científico, Universidad de Salamanca, Salamanca, Spain
| | - Isabel C F R Ferreira
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, Bragança, Portugal
| | - Sandra Cabo Verde
- Centro de Ciências e Tecnologias Nucleares (C2TN), Instituto Superior Técnico, Universidade de Lisboa, Loures, Portugal
| | - Lillian Barros
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, Bragança, Portugal
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18
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Finicelli M, Squillaro T, Galderisi U, Peluso G. Polyphenols, the Healthy Brand of Olive Oil: Insights and Perspectives. Nutrients 2021; 13:3831. [PMID: 34836087 PMCID: PMC8624306 DOI: 10.3390/nu13113831] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 10/18/2021] [Accepted: 10/25/2021] [Indexed: 12/13/2022] Open
Abstract
Given their beneficial potential on human health, plant food bioactive molecules are important components influencing nutrition. Polyphenols have been widely acknowledged for their potentially protective role against several complex diseases. In particular, the polyphenols of olive oil (OOPs) emerge as the key components of many healthy diets and have been widely studied for their beneficial properties. The qualitative and quantitative profile defining the composition of olive oil phenolic molecules as well as their absorbance and metabolism once ingested are key aspects that need to be considered to fully understand the health potential of these molecules. In this review, we provide an overview of the key aspects influencing these variations by focusing on the factors influencing the biosynthesis of OOPs and the findings about their absorption and metabolism. Despite the encouraging evidence, the health potential of OOPs is still debated due to limitations in current studies. Clinical trials are necessary to fully understand and validate the beneficial effects of olive oil and OOPs on human health. We provide an update of the clinical trials based on olive oil and/or OOPs that aim to understand their beneficial effects. Tailored studies are needed to standardize the polyphenolic distribution and understand the variables associated with phenol-enriched OO. An in-depth knowledge of the steps that occur following polyphenol ingestion may reveal useful insights to be used in clinical settings for the prevention and treatment of many diseases.
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Affiliation(s)
- Mauro Finicelli
- Research Institute on Terrestrial Ecosystems (IRET), National Research Council of Italy (CNR), Via Pietro Castellino 111, 80131 Naples, Italy
| | - Tiziana Squillaro
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Via Santa Maria di Costantinopoli 16, 80138 Naples, Italy; (T.S.); (U.G.)
| | - Umberto Galderisi
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Via Santa Maria di Costantinopoli 16, 80138 Naples, Italy; (T.S.); (U.G.)
| | - Gianfranco Peluso
- Research Institute on Terrestrial Ecosystems (IRET), National Research Council of Italy (CNR), Via Pietro Castellino 111, 80131 Naples, Italy
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19
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Hsu ML, Huang WC, Zhou YR, Hu S, Huang CH, Wu SJ. Oleuropein Protects Human Retinal Pigment Epithelium Cells from IL-1β-Induced Inflammation by Blocking MAPK/NF-κB Signaling Pathways. Inflammation 2021; 45:297-307. [PMID: 34613549 DOI: 10.1007/s10753-021-01546-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 07/27/2021] [Accepted: 08/16/2021] [Indexed: 11/25/2022]
Abstract
Proinflammatory mediators such as interleukin (IL)-1β cause retinal pigment epithelium (RPE) inflammation, which is related to visual deterioration, including age-related macular degeneration and diabetic retinopathy. Oleuropein is a polyphenol compound that shows potent anti-inflammatory, antioxidant, and anti-cancer activities, but its effects on IL-1β-induced inflammation have not been examined in the adult RPE cell line ARPE-19. Here, we assessed the ability of oleuropein to attenuate this inflammation in ARPE-19 cells. IL-1β induced secretion of the inflammatory cytokines IL-6, monocyte chemoattractant protein-1 (MCP)-1, and soluble intercellular adhesion molecule (sICAM)-1. As measured by enzyme-linked immunosorbent assay, oleuropein significantly inhibited levels of all three proteins and led to decreased monocyte adhesiveness to ARPE-19 cells. To clarify the underlying anti-inflammatory mechanisms, we used western blots to evaluate the effect of oleuropein on inactivation of the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. The results showed that oleuropein significantly decreased levels of the inflammatory mediator cyclooxygenase-2 and increased anti-inflammatory protein HO-1 expression. We next examined if the anti-inflammatory activity of oleuropein arises via inactivated NF-κB. We found that suppressing phosphorylation of the JNK1/2 and p38 MAPK signaling pathways inhibited IL-6, MCP-1, and sICAM-1 secretion, implicating these pathways and NF-κB suppression in the effects of oleuropein. These results indicate that oleuropein shows potential for the prevention and treatment of inflammatory diseases of the retina.
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Affiliation(s)
- Ming-Lung Hsu
- Department of Nutrition and Health Sciences, Research Center for Food and Cosmetic Safety, and Research Center for Chinese Herbal Medicine, College of Human Ecology, Guishan Dist, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd, Taoyuan City, 33303, Taiwan
| | - Wen-Chung Huang
- Graduate Institute of Health Industry Technology, Research Center for Industry of Human Ecology, Research Center for Chinese Herbal Medicine, College of Human Ecology, Guishan Dist, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd, Taoyuan City, 33303, Taiwan
- Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Guishan Dist, Chang Gung Memorial Hospital, Linkou, 33303, Taiwan
| | - Yi-Rong Zhou
- Department of Nutrition and Health Sciences, Research Center for Food and Cosmetic Safety, and Research Center for Chinese Herbal Medicine, College of Human Ecology, Guishan Dist, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd, Taoyuan City, 33303, Taiwan
| | - Sindy Hu
- Aesthetic Medical Center, Department of Dermatology, Chang Gung Memorial Hospital, Guishan Dist, Taoyuan, 33303, Taiwan
| | - Chun-Hsun Huang
- Aesthetic Medical Center, Department of Dermatology, Chang Gung Memorial Hospital, Guishan Dist, Taoyuan, 33303, Taiwan.
- Department of Cosmetic Science, Research Center for Food and Cosmetic Safety, and Research Center for Chinese Herbal Medicine, College of Human Ecology, Guishan Dist, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd, Taoyuan City, 33303, Taiwan.
- Department of Nutrition and Health Sciences, Research Center for Food and Cosmetic Safety, and Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd., Guishan Dist., Taoyuan City, 33303, Taiwan.
| | - Shu-Ju Wu
- Department of Nutrition and Health Sciences, Research Center for Food and Cosmetic Safety, and Research Center for Chinese Herbal Medicine, College of Human Ecology, Guishan Dist, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd, Taoyuan City, 33303, Taiwan.
- Aesthetic Medical Center, Department of Dermatology, Chang Gung Memorial Hospital, Guishan Dist, Taoyuan, 33303, Taiwan.
- Department of Nutrition and Health Sciences, Research Center for Food and Cosmetic Safety, and Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd., Guishan Dist., Taoyuan City, 33303, Taiwan.
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20
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Rocha S, Oskolkova O, de Freitas V, Reis A. (Poly)phenol-Rich Diets in the Management of Endothelial Dysfunction in Diabetes Mellitus: Biological Properties in Cultured Endothelial Cells. Mol Nutr Food Res 2021; 65:e2001130. [PMID: 34050718 DOI: 10.1002/mnfr.202001130] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 05/06/2021] [Indexed: 01/01/2023]
Abstract
Processed and ready-to-eat foods become routinely consumed resulting in a sharp rise of sugar intake in people's daily diets. The inclusion of fresh fruits and vegetables rich in (poly)phenols has been encouraged by the World Health Organization (WHO) as part of the daily choices to ameliorate endothelial dysfunction and ease the socio-economic burden of diabetes. Research in Food, Nutrition, and Cell Metabolism areas is revealing that the health benefits of (poly)phenol-rich foods go beyond their antioxidant properties and are in fact key modulators of redox and glycaemia status, and inflammatory response contributing to improved endothelial function and vascular health in diabetes. Other beneficial aspects include appetite modulation, regulation of hydrolytic enzymes involved in sugar and lipid metabolism, and mediation of cell-cell aggregation events. This work overviews the current knowledge on the biological properties of ingested (poly)phenols in cultured endothelial cells with emphasis on the circulating (poly)phenols, providing support to (poly)phenol-rich diets as alternatives to drug-based therapies in the prevention, treatment, and management of diabetes. A critical evaluation on the caveats and challenges involve in current experimental cell-based designs and approaches adopted is also discussed.
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Affiliation(s)
- Sara Rocha
- REQUIMTE/LAQV, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, Porto, 4169-007, Portugal
| | - Olga Oskolkova
- Division of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, University of Graz, Humboldtstrasse 46/III, Graz, 8010, Austria
| | - Victor de Freitas
- REQUIMTE/LAQV, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, Porto, 4169-007, Portugal
| | - Ana Reis
- REQUIMTE/LAQV, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, Porto, 4169-007, Portugal
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Danielewski M, Matuszewska A, Szeląg A, Sozański T. The Impact of Anthocyanins and Iridoids on Transcription Factors Crucial for Lipid and Cholesterol Homeostasis. Int J Mol Sci 2021; 22:6074. [PMID: 34199904 PMCID: PMC8200123 DOI: 10.3390/ijms22116074] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/29/2021] [Accepted: 06/03/2021] [Indexed: 12/17/2022] Open
Abstract
Nutrition determines our health, both directly and indirectly. Consumed foods affect the functioning of individual organs as well as entire systems, e.g., the cardiovascular system. There are many different diets, but universal guidelines for proper nutrition are provided in the WHO healthy eating pyramid. According to the latest version, plant products should form the basis of our diet. Many groups of plant compounds with a beneficial effect on human health have been described. Such groups include anthocyanins and iridoids, for which it has been proven that their consumption may lead to, inter alia, antioxidant, cholesterol and lipid-lowering, anti-obesity and anti-diabetic effects. Transcription factors directly affect a number of parameters of cell functions and cellular metabolism. In the context of lipid and cholesterol metabolism, five particularly important transcription factors can be distinguished: liver X receptor (LXR), peroxisome proliferator-activated receptor-α (PPAR-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element-binding protein 1c (SREBP-1c). Both anthocyanins and iridoids may alter the expression of these transcription factors. The aim of this review is to collect and systematize knowledge about the impact of anthocyanins and iridoids on transcription factors crucial for lipid and cholesterol homeostasis.
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Affiliation(s)
- Maciej Danielewski
- Department of Pharmacology, Wroclaw Medical University, Jana Mikulicza-Radeckiego 2, 50-345 Wroclaw, Poland; (A.M.); (A.S.); (T.S.)
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Going "Green" in the Prevention and Management of Atherothrombotic Diseases: The Role of Dietary Polyphenols. J Clin Med 2021; 10:jcm10071490. [PMID: 33916712 PMCID: PMC8038361 DOI: 10.3390/jcm10071490] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 03/24/2021] [Accepted: 03/27/2021] [Indexed: 02/06/2023] Open
Abstract
During the 20th century processed and ready-to-eat foods became routinely consumed resulting in a sharp rise of fat, salt, and sugar intake in people's diets. Currently, the global incidence of obesity, raised blood lipids, hypertension, and diabetes in an increasingly aged population contributes to the rise of atherothrombotic events and cardiovascular diseases (CVD) mortality. Drug-based therapies are valuable strategies to tackle and help manage the socio-economic impact of atherothrombotic disorders though not without adverse side effects. The inclusion of fresh fruits and vegetables rich in flavonoids to human diets, as recommended by WHO offers a valuable nutritional strategy, alternative to drug-based therapies, to be explored in the prevention and management of atherothrombotic diseases at early stages. Though polyphenols are mostly associated to color and taste in foods, food flavonoids are emerging as modulators of cholesterol biosynthesis, appetite and food intake, blood pressure, platelet function, clot formation, and anti-inflammatory signaling, supporting the health-promoting effects of polyphenol-rich diets in mitigating the impact of risk factors in atherothrombotic disorders and CVD events. Here we overview the current knowledge on the effect of polyphenols particularly of flavonoid intake on the atherothrombotic risk factors and discuss the caveats and challenges involved with current experimental cell-based designs.
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Rey AI, De Cara A, Segura JF, Martí P, Hechavarría T, Calvo L. Dietary oleuropein extract supplementation and its combination with α-tocopheryl acetate and selenium modifies the free fatty acid profile of pork and improves its stability. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2021; 101:2337-2344. [PMID: 33006761 DOI: 10.1002/jsfa.10855] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 08/27/2020] [Accepted: 10/02/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND Olive-derived antioxidants have been shown to affect the oxidative status of meat and have also been associated with greater consumption of glucose, which might affect glycogen stores and muscle characteristics. This study evaluated the effect of oleuropein extract supplementation (OLE) versus vitamin E + Se (VE), and their combination (VEOLE), in pig diets, on pH, drip loss, the proportion of free fatty acids, and meat stability, and their prediction by blood oxidative status markers. RESULTS The drip loss of muscle was lower in antioxidant-supplemented groups when compared with controls. α-Tocopherol concentration and total fatty acids profile were not affected by dietary oleuropein supplementation. However, OLE and VEOLE had lower free n-3 polyunsaturated fatty acid (PUFA) levels when compared with VE and tended to have higher free monounsaturated fatty acid (MUFA) levels. Furthermore, the VEOLE group had lower free n-6 PUFA levels when compared with controls or VE, whereas the OLE group had intermediated values. Muscle samples from pigs subjected to the antioxidant-mixed supplementation (VEOLE) had lower malondialdehyde concentration when compared with the others. The VE and OLE groups showed intermediate malondialdehyde values. Chilled meat stability was highly correlated with antioxidant status in vivo. CONCLUSION The administration of 96 mg oleuropein kg-1 feed produced similar meat quality characteristics as the use of 100 mg kg-1 α-tocopheryl acetate +0.26 mg kg-1 sodium selenite and it would be an interesting alternative in Mediterranean countries. The VEOLE group was the most effective for reducing lipid oxidation and for the production of polyunsaturated free fatty acids in meat, which would result in lower rancidity formation and better aroma development in products. © 2020 Society of Chemical Industry.
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Affiliation(s)
- Ana I Rey
- Dpto. Producción Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain
| | - Almudena De Cara
- Dpto. Producción Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain
| | - José Francisco Segura
- Dpto. Producción Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain
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Thyroid-Modulating Activities of Olive and Its Polyphenols: A Systematic Review. Nutrients 2021; 13:nu13020529. [PMID: 33561976 PMCID: PMC7915253 DOI: 10.3390/nu13020529] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 01/30/2021] [Accepted: 02/04/2021] [Indexed: 12/11/2022] Open
Abstract
Olive oil, which is commonly used in the Mediterranean diet, is known for its health benefits related to the reduction of the risks of cancer, coronary heart disease, hypertension, and neurodegenerative disease. These unique properties are attributed to the phytochemicals with potent antioxidant activities in olive oil. Olive leaf also harbours similar bioactive compounds. Several studies have reported the effects of olive phenolics, olive oil, and leaf extract in the modulation of thyroid activities. A systematic review of the literature was conducted to identify relevant studies on the effects of olive derivatives on thyroid function. A comprehensive search was conducted in October 2020 using the PubMed, Scopus, and Web of Science databases. Cellular, animal, and human studies reporting the effects of olive derivatives, including olive phenolics, olive oil, and leaf extracts on thyroid function were considered. The literature search found 445 articles on this topic, but only nine articles were included based on the inclusion and exclusion criteria. All included articles were animal studies involving the administration of olive oil, olive leaf extract, or olive pomace residues orally. These olive derivatives were consistently demonstrated to have thyroid-stimulating activities in euthyroid or hypothyroid animals, but their mechanisms of action are unknown. Despite the positive results, validation of the beneficial health effects of olive derivatives in the human population is lacking. In conclusion, olive derivatives, especially olive oil and leaf extract, could stimulate thyroid function. Olive pomace residue is not suitable for pharmaceutical or health supplementation purposes. Therapeutic applications of olive oil and leaf extract, especially in individuals with hypothyroidism, require further validation through human studies.
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Jakab J, Miškić B, Mikšić Š, Juranić B, Ćosić V, Schwarz D, Včev A. Adipogenesis as a Potential Anti-Obesity Target: A Review of Pharmacological Treatment and Natural Products. Diabetes Metab Syndr Obes 2021; 14:67-83. [PMID: 33447066 PMCID: PMC7802907 DOI: 10.2147/dmso.s281186] [Citation(s) in RCA: 152] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 12/09/2020] [Indexed: 12/14/2022] Open
Abstract
Obesity is recognized as a severe threat to overall human health and is associated with type 2 diabetes mellitus, dyslipidemia, hypertension, and cardiovascular diseases. Abnormal expansion of white adipose tissue involves increasing the existing adipocytes' cell size or increasing the number through the differentiation of new adipocytes. Adipogenesis is a process of proliferation and differentiation of adipocyte precursor cells in mature adipocytes. As a key process in determining the number of adipocytes, it is a possible therapeutic approach for obesity. Therefore, it is necessary to identify the molecular mechanisms involved in adipogenesis that could serve as suitable therapeutic targets. Reducing bodyweight is regarded as a major health benefit. Limited efficacy and possible side effects and drug interactions of available anti-obesity treatment highlight a constant need for finding novel efficient and safe anti-obesity ingredients. Numerous studies have recently investigated the inhibitory effects of natural products on adipocyte differentiation and lipid accumulation. Possible anti-obesity effects of natural products include the induction of apoptosis, cell-cycle arrest or delayed progression, and interference with transcription factor cascade or intracellular signaling pathways during the early phase of adipogenesis.
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Affiliation(s)
- Jelena Jakab
- Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Correspondence: Jelena Jakab Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Crkvena 21, Osijek31 000, CroatiaTel +385 91 224 1502 Email
| | - Blaženka Miškić
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Department of Internal Medicine, General Hospital “Dr. Josip Benčević”, Slavonski Brod, Croatia
| | - Štefica Mikšić
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Brankica Juranić
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Department of Cardiology, University Hospital Osijek, Osijek, Croatia
| | - Vesna Ćosić
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Dragan Schwarz
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Special Hospital Radiochirurgia Zagreb, Zagreb, Croatia
| | - Aleksandar Včev
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
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Tyrosol May Prevent Obesity by Inhibiting Adipogenesis in 3T3-L1 Preadipocytes. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:4794780. [PMID: 33376578 PMCID: PMC7746459 DOI: 10.1155/2020/4794780] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 11/08/2020] [Accepted: 11/19/2020] [Indexed: 02/07/2023]
Abstract
Tyrosol (TR), a major polyphenol found in extra virgin olive oil (EVOO), exerts several antioxidant effects. However, only scarce evidences are present regarding its activity on adipocytes and obesity. This study evaluated the role of TR in adipogenesis. Murine 3T3-L1 preadipocytes were incubated with TR (300 and 500 μM), and TR administration inhibited adipogenesis by downregulation of several adipogenic factors (leptin and aP2) and transcription factors (C/EBPα, PPARγ, SREBP1c, and Glut4) and by modulation of the histone deacetylase sirtuin 1. After complete differentiation, adipocytes treated with 300 and 500 μM TR showed a reduction of 20% and 30% in lipid droplets, respectively. Intracellular triglycerides were significantly reduced after TR treatment (p < 0.05). Mature adipocytes treated with TR at 300 and 500 μM showed a marked decrease in the inflammatory state and oxidative stress as shown by the modulation of specific biomarkers (TNF, IL6, ROS, and SOD2). TR treatment also acted on the early stage of differentiation by reducing cell proliferation (~40%) and inducing cell cycle arrest during Mitotic Expansion Clonal (first 48 h of differentiation), as shown by the increase in both S1 phase and p21 protein expression. We also showed that TR induced lipolysis by activating the AMPK-ATGL-HSL pathway. In conclusion, we provided evidence that TR reduces 3T3-L1 differentiation through downregulation of adipogenic proteins, inflammation, and oxidative stress. Moreover, TR may trigger adipose tissue browning throughout the induction of the AMPK-ATGL-UCP1 pathway and, subsequently, may have promise as a potential therapeutic agent for the treatment and prevention of obesity.
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Olive Leaf Extract, from Olea europaea L., Reduces Palmitate-Induced Inflammation via Regulation of Murine Macrophages Polarization. Nutrients 2020; 12:nu12123663. [PMID: 33260769 PMCID: PMC7761141 DOI: 10.3390/nu12123663] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 11/22/2020] [Accepted: 11/23/2020] [Indexed: 12/12/2022] Open
Abstract
Olive tree (Olea europaea L.) leaves are an abundant source of bioactive compounds with several beneficial effects for human health. Recently, the effect of olive leaf extract in obesity has been studied. However, the molecular mechanism in preventing obesity-related inflammation has not been elucidated. Obesity is a state of chronic low-grade inflammation and is associated with an increase of pro-inflammatory M1 macrophages infiltration in the adipose tissue. In the current study, we explored Olea europaea L. leaf extract (OLE) anti-inflammatory activity using an in vitro model of obesity-induced inflammation obtained by stimulating murine macrophages RAW 264.7 with high dose of the free fatty acid palmitate. We found that OLE significantly suppressed the induction of pro-inflammatory mediators, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, nitric oxide (NO), prostaglandin E2 (PGE2) and reactive oxygen species (ROS), while it enhanced the anti-inflammatory cytokine, IL-10. Moreover, we demonstrated that OLE reduced the oxidative stress induced by palmitate in macrophages by regulating the NF-E2-related factor 2 (NRF2)−Kelch-like ECH-associated protein 1 (KEAP1) pathway. Finally, we showed that OLE promoted the shift of M1 macrophage toward less inflammatory M2-cells via the modulation of the associated NF-κB and proliferator-activated receptor gamma (PPARγ) signaling pathways. Thereby, our findings shed light on the potential therapeutic feature of OLE in recovering obesity-associated inflammation via regulating M1/M2 status.
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Giacometti J, Muhvić D, Grubić-Kezele T, Nikolić M, Šoić-Vranić T, Bajek S. Olive Leaf Polyphenols (OLPs) Stimulate GLUT4 Expression and Translocation in the Skeletal Muscle of Diabetic Rats. Int J Mol Sci 2020; 21:ijms21238981. [PMID: 33256066 PMCID: PMC7729747 DOI: 10.3390/ijms21238981] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 11/24/2020] [Indexed: 12/18/2022] Open
Abstract
Skeletal muscles are high-insulin tissues responsible for disposing of glucose via the highly regulated process of facilitated glucose transporter 4 (GLUT4). Impaired insulin action in diabetes, as well as disorders of GLUT4 vesicle trafficking in the muscle, are involved in defects in insulin-stimulated GLUT4 translocation. Since the Rab GTPases are the main regulators of vesicular membrane transport in exo- and endo-cytosis, in the present work, we studied the effect of olive leaf polyphenols (OLPs) on Rab8A, Rab13, and Rab14 proteins of the rat soleus muscle in a model of streptozotocin (SZT)-induced diabetes (DM) in a dose-dependent manner. Glucose, cholesterol, and triglyceride levels were determined in the blood, morphological changes of the muscle tissue were captured by hematoxylin and eosin histological staining, and expression of GLUT4, Rab8A, Rab13, and Rab14 proteins were analyzed in the rat soleus muscle by the immunofluorescence staining and immunoblotting. OLPs significantly reduced blood glucose level in all treated groups. Furthermore, significantly reduced blood triglycerides were found in the groups with the lowest and highest OLPs treatment. The dynamics of activation of Rab8A, Rab13, and Rab14 was OLPs dose-dependent and more effective at higher OLP doses. Thus, these results indicate a beneficial role of phenolic compounds from the olive leaf in the regulation of glucose homeostasis in the skeletal muscle.
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Affiliation(s)
- Jasminka Giacometti
- Department of Biotechnology, University of Rijeka, Radmile Matejčić 2, 51000 Rijeka, Croatia
- Correspondence: ; Tel.: +385-51-584-557
| | - Damir Muhvić
- Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia; (D.M.); (T.G.-K.)
| | - Tanja Grubić-Kezele
- Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia; (D.M.); (T.G.-K.)
- Clinical Department for Clinical Microbiology, Clinical Hospital Center Rijeka, Krešimirova 42, 51000 Rijeka, Croatia
| | - Marina Nikolić
- Department of Anatomy, Faculty of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia; (M.N.); (T.Š.-V.); (S.B.)
| | - Tamara Šoić-Vranić
- Department of Anatomy, Faculty of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia; (M.N.); (T.Š.-V.); (S.B.)
| | - Snježana Bajek
- Department of Anatomy, Faculty of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia; (M.N.); (T.Š.-V.); (S.B.)
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4β-Hydroxywithanolide E and withanolide E from Physalis peruviana L. inhibit adipocyte differentiation of 3T3-L1 cells through modulation of mitotic clonal expansion. J Nat Med 2020; 75:232-239. [PMID: 33200287 DOI: 10.1007/s11418-020-01458-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 10/05/2020] [Indexed: 01/13/2023]
Abstract
Obesity is a risk factor for many diseases, including type 2 diabetes and cardiovascular disease, and is related to the rising morbidity and mortality. Discovery of agents targeting adipogenesis, especially from natural sources, is important for the treatment of obesity. Here, we aimed to identify anti-adipogenic substances in methanol extracts of Physalis peruviana and to investigate their effect, along with underlying mechanisms. Activity-guided fractionation of the extract revealed 4β-hydroxywithanolide E (HWE) and withanolide E (WE) as the adipogenesis inhibitors. Both compounds suppressed mRNA expression of central adipogenic transcription factors, peroxisome proliferator-activated receptor γ, and CCAAT/enhancer-binding protein α in the early stage of adipocyte differentiation. The inhibitory action of these two withanolides on adipogenesis was largely limited to this stage. The proliferation of preadipocytes was markedly suppressed by treatment with HWE and WE for 24 and 48 h in the differentiation medium, and cell-cycle arrest in the G0/G1 phase was observed. Therefore, our results suggested that withanolides from P. peruviana to be novel anti-adipogenic compounds that modulate mitotic clonal expansion.
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Vidhya R, Anuradha CV. Anti-inflammatory effects of troxerutin are mediated through elastase inhibition. Immunopharmacol Immunotoxicol 2020; 42:423-435. [PMID: 32762381 DOI: 10.1080/08923973.2020.1806870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
CONTEXT Obesity is a chronic low-grade inflammatory state associated with immune cell infiltration into the adipose tissue (AT). We hypothesize that the anti-obesity and anti-inflammatory effects of troxerutin (TX) are mediated through inhibition of elastase. OBJECTIVE To determine the inhibitory effect of TX on elastase in vitro and in tumor necrosis factor alpha (TNFα) induced 3T3-L1 adipocytes and the molecular interaction of TX with human neutrophil elastase (HNE). MATERIALS AND METHODS Differentiated 3T3-L1 adipocytes were pretreated with TX, elastatinal (ELAS) or sodium salicylate (SAL) before exposure to TNFα. Lipid accumulation, reactive oxygen species (ROS) generation and oxidant-antioxidant balance were examined. The mRNA and protein expression of TNFα, interleukin-6, monocyte chemoattractant protein-1, adiponectin, leptin, resistin, chemerin, and elastase were analyzed. Elastase inhibition by TX and ELAS in a cell free system and docking studies for HNE with TX and ELAS were performed. RESULTS TX, ELAS or SAL pretreatment had lowered lipid droplets formation and TG content. TX suppressed ROS generation, oxidative stress and improved antioxidant status. The expression of inflammatory cytokines and elastase was downregulated while that of adiponectin was upregulated by TX. The concentration required to produce 50% inhibition in vitro (IC50) was 11.5 μM for TX and 16.9 μM for ELAS. TX showed hydrogen bonding and hydrophobic interactions with elastase. DISCUSSION TNFα induces inflammation of 3T3-L1 cells through elastase activation. TX inhibits elastase activity, downregulates expression and binds with elastase. CONCLUSION The antioxidant and anti-inflammatory activities of TX in AT could be of relevance in the management of obesity.
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Affiliation(s)
- Ramachandran Vidhya
- Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar, Tamil Nadu, India
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Farràs M, Martinez-Gili L, Portune K, Arranz S, Frost G, Tondo M, Blanco-Vaca F. Modulation of the Gut Microbiota by Olive Oil Phenolic Compounds: Implications for Lipid Metabolism, Immune System, and Obesity. Nutrients 2020; 12:nu12082200. [PMID: 32718098 PMCID: PMC7468985 DOI: 10.3390/nu12082200] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Accepted: 07/20/2020] [Indexed: 12/11/2022] Open
Abstract
There is extensive information of the beneficial effects of virgin olive oil (VOO), especially on cardiovascular diseases. Some VOO healthy properties have been attributed to their phenolic-compounds (PCs). The aim of this review is to present updated data on the effects of olive oil (OO) PCs on the gut microbiota, lipid metabolism, immune system, and obesity, as well as on the crosstalk among them. We summarize experiments and clinical trials which assessed the specific effects of the olive oil phenolic-compounds (OOPCs) without the synergy with OO-fats. Several studies have demonstrated that OOPC consumption increases Bacteroidetes and/or reduces the Firmicutes/Bacteroidetes ratio, which have both been related to atheroprotection. OOPCs also increase certain beneficial bacteria and gut-bacteria diversity which can be therapeutic for lipid-immune disorders and obesity. Furthermore, some of the mechanisms implicated in the crosstalk between OOPCs and these disorders include antimicrobial-activity, cholesterol microbial metabolism, and metabolites produced by bacteria. Specifically, OOPCs modulate short-chain fatty-acids produced by gut-microbiota, which can affect cholesterol metabolism and the immune system, and may play a role in weight gain through promoting satiety. Since data in humans are scarce, there is a necessity for more clinical trials designed to assess the specific role of the OOPCs in this crosstalk.
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Affiliation(s)
- Marta Farràs
- Institut de Recerca de l’Hospital Santa Creu i Sant Pau, Institut d’Investigacions Biomèdiques (IIB) Sant Pau, 08041 Barcelona, Spain
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 08907 Barcelona, Spain;
- Correspondence: ; Tel.: +34-935537595
| | - Laura Martinez-Gili
- Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK;
| | - Kevin Portune
- AZTI, Food Research, Basque Research and Technology Alliance (BRTA), Parque Tecnológico de Bizkaia, AstondoBidea, Edificio 609, 48160 Derio, Spain; (K.P.); (S.A.)
| | - Sara Arranz
- AZTI, Food Research, Basque Research and Technology Alliance (BRTA), Parque Tecnológico de Bizkaia, AstondoBidea, Edificio 609, 48160 Derio, Spain; (K.P.); (S.A.)
| | - Gary Frost
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK;
| | - Mireia Tondo
- Hospital de la Santa Creu i Sant Pau, Servei de Bioquímica-Institut d’Investigacions Biomèdiques (IIB) Sant Pau, 08041 Barcelona, Spain;
| | - Francisco Blanco-Vaca
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 08907 Barcelona, Spain;
- Hospital de la Santa Creu i Sant Pau, Servei de Bioquímica-Institut d’Investigacions Biomèdiques (IIB) Sant Pau, 08041 Barcelona, Spain;
- Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
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Reis A, Perez-Gregorio R, Mateus N, de Freitas V. Interactions of dietary polyphenols with epithelial lipids: advances from membrane and cell models in the study of polyphenol absorption, transport and delivery to the epithelium. Crit Rev Food Sci Nutr 2020; 61:3007-3030. [PMID: 32654502 DOI: 10.1080/10408398.2020.1791794] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Currently, diet-related diseases such as diabetes, obesity, hypertension, and cardiovascular diseases account for 70% of all global deaths. To counteract the rising prevalence of non-communicable diseases governments are investing in persuasive educational campaigns toward the ingestion of fresh fruits and vegetables. The intake of dietary polyphenols abundant in Mediterranean and Nordic-type diets holds great potential as nutritional strategies in the management of diet-related diseases. However, the successful implementation of healthy nutritional strategies relies on a pleasant sensory perception in the mouth able to persuade consumers to adopt polyphenol-rich diets and on a deeper understanding on the chemical modifications, that affect not only their chemical properties but also their physical interaction with epithelial lipids and in turn their permeability, location within the lipid bilayer, toxicity and biological activity, and fate during absorption at the gastro-intestinal epithelium, transport in circulation and delivery to the endothelium. In this paper, we review the current knowledge on the interactions between polyphenols and their metabolites with membrane lipids in artificial membranes and epithelial cell models (oral, stomach, gut and endothelium) and the findings from polyphenol-lipid interactions to physiological processes such as oral taste perception, gastrointestinal absorption and endothelial health. Finally, we discuss the limitations and challenges associated with the current experimental approaches in membrane and cell model studies and the potential of polyphenol-rich diets in the quest for personalized nutritional strategies ("personalized nutrition") to assist in the prevention, treatment, and management of non-communicable diseases in an increasingly aged population.
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Affiliation(s)
- Ana Reis
- Department Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal
| | - Rosa Perez-Gregorio
- Department Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal
| | - Nuno Mateus
- REQUIMTE/LAQV, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Portugal
| | - Victor de Freitas
- REQUIMTE/LAQV, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Portugal
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Leri M, Scuto M, Ontario ML, Calabrese V, Calabrese EJ, Bucciantini M, Stefani M. Healthy Effects of Plant Polyphenols: Molecular Mechanisms. Int J Mol Sci 2020; 21:E1250. [PMID: 32070025 PMCID: PMC7072974 DOI: 10.3390/ijms21041250] [Citation(s) in RCA: 272] [Impact Index Per Article: 54.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 02/08/2020] [Accepted: 02/10/2020] [Indexed: 02/08/2023] Open
Abstract
The increasing extension in life expectancy of human beings in developed countries is accompanied by a progressively greater rate of degenerative diseases associated with lifestyle and aging, most of which are still waiting for effective, not merely symptomatic, therapies. Accordingly, at present, the recommendations aimed at reducing the prevalence of these conditions in the population are limited to a safer lifestyle including physical/mental exercise, a reduced caloric intake, and a proper diet in a convivial environment. The claimed health benefits of the Mediterranean and Asian diets have been confirmed in many clinical trials and epidemiological surveys. These diets are characterized by several features, including low meat consumption, the intake of oils instead of fats as lipid sources, moderate amounts of red wine, and significant amounts of fresh fruit and vegetables. In particular, the latter have attracted popular and scientific attention for their content, though in reduced amounts, of a number of molecules increasingly investigated for their healthy properties. Among the latter, plant polyphenols have raised remarkable interest in the scientific community; in fact, several clinical trials have confirmed that many health benefits of the Mediterranean/Asian diets can be traced back to the presence of significant amounts of these molecules, even though, in some cases, contradictory results have been reported, which highlights the need for further investigation. In light of the results of these trials, recent research has sought to provide information on the biochemical, molecular, epigenetic, and cell biology modifications by plant polyphenols in cell, organismal, animal, and human models of cancer, metabolic, and neurodegenerative pathologies, notably Alzheimer's and Parkinson disease. The findings reported in the last decade are starting to help to decipher the complex relations between plant polyphenols and cell homeostatic systems including metabolic and redox equilibrium, proteostasis, and the inflammatory response, establishing an increasingly solid molecular basis for the healthy effects of these molecules. Taken together, the data currently available, though still incomplete, are providing a rationale for the possible use of natural polyphenols, or their molecular scaffolds, as nutraceuticals to contrast aging and to combat many associated pathologies.
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Affiliation(s)
- Manuela Leri
- Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Viale Morgagni 50, 50134 Florence, Italy; (M.L.); (M.B.); (M.S.)
- Department of Neuroscience, Psychology, Drug Research and Child Health, University of Firenze, 50139 Florence, Italy
| | - Maria Scuto
- Department of Biomedical and Biotechnological Sciences, University of Catania, Torre Biologica, Via Santa Sofia, 97-95125 Catania, Italy; (M.S.); (M.L.O.); (V.C.)
| | - Maria Laura Ontario
- Department of Biomedical and Biotechnological Sciences, University of Catania, Torre Biologica, Via Santa Sofia, 97-95125 Catania, Italy; (M.S.); (M.L.O.); (V.C.)
| | - Vittorio Calabrese
- Department of Biomedical and Biotechnological Sciences, University of Catania, Torre Biologica, Via Santa Sofia, 97-95125 Catania, Italy; (M.S.); (M.L.O.); (V.C.)
| | - Edward J. Calabrese
- Department of Environmental Health Sciences, School of Public Health and Health Science, University of Massachusetts, Amherst, MA 01003, USA
| | - Monica Bucciantini
- Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Viale Morgagni 50, 50134 Florence, Italy; (M.L.); (M.B.); (M.S.)
| | - Massimo Stefani
- Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Viale Morgagni 50, 50134 Florence, Italy; (M.L.); (M.B.); (M.S.)
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Colocynth (Citrullus colocynthis) seed extracts attenuate adipogenesis by down-regulating PPARγ/ SREBP-1c and C/EBPα in 3T3-L1 cells. FOOD BIOSCI 2020. [DOI: 10.1016/j.fbio.2019.100491] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Changes in Plasma Fatty Acids, Free Amino Acids, Antioxidant Defense, and Physiological Stress by Oleuropein Supplementation in Pigs Prior to Slaughter. Antioxidants (Basel) 2020; 9:antiox9010056. [PMID: 31936246 PMCID: PMC7022758 DOI: 10.3390/antiox9010056] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 12/30/2019] [Accepted: 12/31/2019] [Indexed: 12/11/2022] Open
Abstract
Olive tree leaves are characterized for having not only a potent antioxidant power but also effects on glucose and lipid metabolism. The impact of the individual oleuropein (OLE), vitamin E + Se (VE), or a combined supplementation of oleuropein, vitamin E, and selenium (VEOLE) was evaluated on pig plasma metabolites under fasting prior to slaughter. VEOLE and OLE had lesser n-3 plasma polyunsaturated fatty acids and greater monounsaturated free fatty acids compared to control. The n-3-fatty acid mobilization was directly correlated with greater cystine and inversely with oxidized glutathione/reduced glutathione (GSSH/GSH) levels. This faster use of n-3 fatty acids might act as an indicator of glutathione synthesis mediated by an increase of cystine in plasma. Different correlations and linear adjustments were observed between plasma antioxidant power and free cystine, free glycine, free glutamine, monounsaturated free fatty acids, and total n-3. The best response to stress was found in VEOLE. Cortisol reached the greatest positive correlation with plasma total n-3 fatty acids, which suggests a faster uptake of n-3 for biological functions such as stress control or energy supply in the brain. From a practical point of view, an enhanced oxidative status as well as control of physiological stress prior to slaughter by the combined antioxidants supplementation might have positive effects on pork quality.
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Casado-Díaz A, Dorado G, Quesada-Gómez JM. Influence of olive oil and its components on mesenchymal stem cell biology. World J Stem Cells 2019; 11:1045-1064. [PMID: 31875868 PMCID: PMC6904865 DOI: 10.4252/wjsc.v11.i12.1045] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 08/29/2019] [Accepted: 11/04/2019] [Indexed: 02/06/2023] Open
Abstract
Extra virgin olive oil is characterized by its high content of unsaturated fatty acid residues in triglycerides, mainly oleic acid, and the presence of bioactive and antioxidant compounds. Its consumption is associated with lower risk of suffering chronic diseases and unwanted processes linked to aging, due to the antioxidant capacity and capability of its components to modulate cellular signaling pathways. Consumption of olive oil can alter the physiology of mesenchymal stem cells (MSCs). This may explain part of the healthy effects of olive oil consumption, such as prevention of unwanted aging processes. To date, there are no specific studies on the action of olive oil on MSCs, but effects of many components of such food on cell viability and differentiation have been evaluated. The objective of this article is to review existing literature on how different compounds of extra virgin olive oil, including residues of fatty acids, vitamins, squalene, triterpenes, pigments and phenols, affect MSC maintenance and differentiation, in order to provide a better understanding of the healthy effects of this food. Interestingly, most studies have shown a positive effect of these compounds on MSCs. The collective findings support the hypothesis that at least part of the beneficial effects of extra virgin olive oil consumption on health may be mediated by its effects on MSCs.
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Affiliation(s)
- Antonio Casado-Díaz
- CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Córdoba 14004, Spain
| | - Gabriel Dorado
- Departement Bioquímica y Biología Molecular, Campus Rabanales C6-1-E17, Campus de Excelencia Internacional Agroalimentario (ceiA3), Universidad de Córdoba, CIBERFES, Córdoba 14071, Spain
| | - José Manuel Quesada-Gómez
- Unidad de Gestión Clínica de Endocrinología y Nutrición, CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Córdoba 14004, Spain.
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Ahamad J, Toufeeq I, Khan MA, Ameen MSM, Anwer ET, Uthirapathy S, Mir SR, Ahmad J. Oleuropein: A natural antioxidant molecule in the treatment of metabolic syndrome. Phytother Res 2019; 33:3112-3128. [DOI: 10.1002/ptr.6511] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2019] [Revised: 07/25/2019] [Accepted: 08/23/2019] [Indexed: 02/03/2023]
Affiliation(s)
- Javed Ahamad
- Faculty of PharmacyTishk International University Erbil Iraq
| | - Ibrahim Toufeeq
- Faculty of PharmacyTishk International University Erbil Iraq
| | - Mohammad Ahmed Khan
- Department of Pharmacology, School of Pharmaceutical Education and ResearchJamia Hamdard New Delhi India
| | | | - Esra T. Anwer
- Faculty of PharmacyTishk International University Erbil Iraq
| | | | - Showkat R. Mir
- Department of Pharmacognosy, School of Pharmaceutical Education and Research (Formerly Faculty of Pharmacy)Jamia Hamdard New Delhi India
| | - Javed Ahmad
- Department of Pharmaceutics, College of PharmacyNajran University Najran Kingdom of Saudi Arabia
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Scoditti E, Carpi S, Massaro M, Pellegrino M, Polini B, Carluccio MA, Wabitsch M, Verri T, Nieri P, De Caterina R. Hydroxytyrosol Modulates Adipocyte Gene and miRNA Expression Under Inflammatory Condition. Nutrients 2019; 11:nu11102493. [PMID: 31627295 PMCID: PMC6836288 DOI: 10.3390/nu11102493] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2019] [Revised: 10/10/2019] [Accepted: 10/15/2019] [Indexed: 12/13/2022] Open
Abstract
Chronic inflammation of the adipose tissue (AT) is a major contributor to obesity-associated cardiometabolic complications. The olive oil polyphenol hydroxytyrosol (HT) contributes to Mediterranean diet cardiometabolic benefits through mechanisms still partially unknown. We investigated HT (1 and 10 μmol/L) effects on gene expression (mRNA and microRNA) related to inflammation induced by 10 ng/mL tumor necrosis factor (TNF)-α in human Simpson–Golabi–Behmel Syndrome (SGBS) adipocytes. At real-time PCR, HT significantly inhibited TNF-α-induced mRNA levels, of monocyte chemoattractant protein-1, C-X-C Motif Ligand-10, interleukin (IL)-1β, IL-6, vascular endothelial growth factor, plasminogen activator inhibitor-1, cyclooxygenase-2, macrophage colony-stimulating factor, matrix metalloproteinase-2, Cu/Zn superoxide dismutase-1, and glutathione peroxidase, as well as surface expression of intercellular adhesion molecule-1, and reverted the TNF-α-mediated inhibition of endothelial nitric oxide synthase, peroxisome proliferator-activated receptor coactivator-1α, and glucose transporter-4. We found similar effects in adipocytes stimulated by macrophage-conditioned media. Accordingly, HT significantly counteracted miR-155-5p, miR-34a-5p, and let-7c-5p expression in both cells and exosomes, and prevented NF-κB activation and production of reactive oxygen species. HT can therefore modulate adipocyte gene expression profile through mechanisms involving a reduction of oxidative stress and NF-κB inhibition. By such mechanisms, HT may blunt macrophage recruitment and improve AT inflammation, preventing the deregulation of pathways involved in obesity-related diseases.
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Affiliation(s)
- Egeria Scoditti
- National Research Council (CNR) Institute of Clinical Physiology (IFC), 73100 Lecce, Italy.
| | - Sara Carpi
- Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.
| | - Marika Massaro
- National Research Council (CNR) Institute of Clinical Physiology (IFC), 73100 Lecce, Italy.
| | - Mariangela Pellegrino
- Laboratory of Applied Physiology, Department of Biological and Environmental Science and Technology (DISTEBA), University of Salento, 73100 Lecce, Italy.
| | - Beatrice Polini
- Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.
| | | | - Martin Wabitsch
- Division of Pediatric Endocrinology, Diabetes and Obesity, Department of Pediatrics and Adolescent Medicine, University of Ulm, 89075 Ulm, Germany.
| | - Tiziano Verri
- Laboratory of Applied Physiology, Department of Biological and Environmental Science and Technology (DISTEBA), University of Salento, 73100 Lecce, Italy.
| | - Paola Nieri
- Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.
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Wu LY, Chen CW, Chen LK, Chou HY, Chang CL, Juan CC. Curcumin Attenuates Adipogenesis by Inducing Preadipocyte Apoptosis and Inhibiting Adipocyte Differentiation. Nutrients 2019; 11:nu11102307. [PMID: 31569380 PMCID: PMC6836120 DOI: 10.3390/nu11102307] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Revised: 08/09/2019] [Accepted: 09/10/2019] [Indexed: 12/23/2022] Open
Abstract
Patients with metabolic syndrome are at an increased risk of developing type 2 diabetes and cardiovascular diseases. The principal risk factor for development of metabolic syndrome is obesity, defined as a state of pathological hyperplasia or/and hypertrophy of adipose tissue. The number of mature adipocytes is determined by adipocyte differentiation from preadipocytes. The purpose of the present study is to investigate the effects of curcumin on adipogenesis and the underlying mechanism. To examine cell toxicity of curcumin, 3T3-L1 preadipocytes were treated with 0–50 µM curcumin for 24, 48, or 72 h, then cell viability was measured using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The effect of curcumin on the cell cycle was determined by flow cytometry. Curcumin-induced cell apoptosis was determined by the TUNEL assay and curcumin-induced caspase activation was measured by immunoblotting. The effect of curcumin on adipocyte differentiation was determined by measuring mitotic clonal expansion (MCE), expression of adipogenic transcription factors, and lipid accumulation. Results showed the viability of preadipocytes was significantly decreased by treatment with 30 µM curcumin, a concentration that caused apoptosis in preadipocytes, as assessed by the TUNEL assay, and caused activation of caspases 8, 9, and 3. A non-cytotoxic dose of curcumin (15 µM) inhibited MCE, downregulated the expression of PPARγ and C/EBPα, prevented differentiation medium-induced β-catenin downregulation, and decreased the lipid accumulation in 3T3-L1 adipocytes. In conclusion, our data show that curcumin can induce preadipocyte apoptosis and inhibit adipocyte differentiation, leading to suppression of adipogenesis.
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Affiliation(s)
- Liang-Yi Wu
- Department of Bioscience Technology, College of Science, Chung-Yuan Christian University, Chung Li 32023, Taiwan.
| | - Chien-Wei Chen
- Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
- College of Human Development and Health, National Taipei University of Nursing and Health Sciences, Taipei 11219, Taiwan.
| | - Luen-Kui Chen
- Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
| | - Hsiang-Yun Chou
- Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
| | - Chih-Ling Chang
- Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
| | - Chi-Chang Juan
- Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
- Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
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Vlavcheski F, Young M, Tsiani E. Antidiabetic Effects of Hydroxytyrosol: In Vitro and In Vivo Evidence. Antioxidants (Basel) 2019; 8:E188. [PMID: 31234300 PMCID: PMC6616959 DOI: 10.3390/antiox8060188] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 06/14/2019] [Accepted: 06/18/2019] [Indexed: 12/12/2022] Open
Abstract
Insulin resistance, a pathological condition characterized by defects in insulin action leads to the development of Type 2 diabetes mellitus (T2DM), a disease which is currently on the rise that pose an enormous economic burden to healthcare systems worldwide. The current treatment and prevention strategies are considerably lacking in number and efficacy and therefore new targeted therapies and preventative strategies are urgently needed. Plant-derived chemicals such as metformin, derived from the French lilac, have been used to treat/manage insulin resistance and T2DM. Other plant-derived chemicals which are not yet discovered, may have superior properties to prevent and manage T2DM and thus research into this area is highly justifiable. Hydroxytyrosol is a phenolic phytochemical found in olive leaves and olive oil reported to have antioxidant, anti-inflammatory, anticancer and antidiabetic properties. The present review summarizes the current in vitro and in vivo studies examining the antidiabetic properties of hydroxytyrosol and investigating the mechanisms of its action.
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Affiliation(s)
- Filip Vlavcheski
- Department of Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada.
- Centre for Bone and Muscle Health, Brock University, St. Catharines, ON L2S 3A1, Canada.
| | - Mariah Young
- Department of Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada.
| | - Evangelia Tsiani
- Department of Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada.
- Centre for Bone and Muscle Health, Brock University, St. Catharines, ON L2S 3A1, Canada.
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Karković Marković A, Torić J, Barbarić M, Jakobušić Brala C. Hydroxytyrosol, Tyrosol and Derivatives and Their Potential Effects on Human Health. Molecules 2019; 24:molecules24102001. [PMID: 31137753 PMCID: PMC6571782 DOI: 10.3390/molecules24102001] [Citation(s) in RCA: 326] [Impact Index Per Article: 54.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 05/17/2019] [Accepted: 05/24/2019] [Indexed: 12/14/2022] Open
Abstract
The Mediterranean diet and olive oil as its quintessential part are almost synonymous with a healthy way of eating and living nowadays. This kind of diet has been highly appreciated and is widely recognized for being associated with many favorable effects, such as reduced incidence of different chronic diseases and prolonged longevity. Although olive oil polyphenols present a minor fraction in the composition of olive oil, they seem to be of great importance when it comes to the health benefits, and interest in their biological and potential therapeutic effects is huge. There is a growing body of in vitro and in vivo studies, as well as intervention-based clinical trials, revealing new aspects of already known and many new, previously unknown activities and health effects of these compounds. This review summarizes recent findings regarding biological activities, metabolism and bioavailability of the major olive oil phenolic compounds—hydroxytyrosol, tyrosol, oleuropein, oleocanthal and oleacein—the most important being their antiatherogenic, cardioprotective, anticancer, neuroprotective and endocrine effects. The evidence presented in the review concludes that these phenolic compounds have great pharmacological potential, however, further studies are still required.
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Affiliation(s)
- Ana Karković Marković
- Faculty of Pharmacy and Biochemistry, University of Zagreb, A.Kovačića 1, 10 000 Zagreb, Croatia.
| | - Jelena Torić
- Faculty of Pharmacy and Biochemistry, University of Zagreb, A.Kovačića 1, 10 000 Zagreb, Croatia.
| | - Monika Barbarić
- Faculty of Pharmacy and Biochemistry, University of Zagreb, A.Kovačića 1, 10 000 Zagreb, Croatia.
| | - Cvijeta Jakobušić Brala
- Faculty of Pharmacy and Biochemistry, University of Zagreb, A.Kovačića 1, 10 000 Zagreb, Croatia.
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Chayaratanasin P, Caobi A, Suparpprom C, Saenset S, Pasukamonset P, Suanpairintr N, Barbieri MA, Adisakwattana S. Clitoria ternatea Flower Petal Extract Inhibits Adipogenesis and Lipid Accumulation in 3T3-L1 Preadipocytes by Downregulating Adipogenic Gene Expression. Molecules 2019; 24:molecules24101894. [PMID: 31108834 PMCID: PMC6571662 DOI: 10.3390/molecules24101894] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 04/28/2019] [Accepted: 05/14/2019] [Indexed: 01/05/2023] Open
Abstract
Clitoria ternatea (commonly known as blue pea) flower petal extract (CTE) is used as a natural colorant in a variety of foods and beverages. The objective of study was to determine the inhibitory effect of CTE on adipogenesis in 3T3-L1 preadipocytes. The phytochemical profiles of CTE were analyzed by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Anti-adipogenesis effect of CTE was measured by using Oil Red O staining, intracellular triglyceride assay, quantitative real-time PCR and western blot analysis in 3T3-L1 adipocytes. Cell cycle studies were performed by flow cytometry. Lipolysis experiments were performed using a colorimetric assay kit. In early stages, CTE demonstrated anti-adipogenic effects through inhibition of proliferation and cell cycle retardation by suppressing expression of phospho-Akt and phospho-ERK1/2 signaling pathway. The results also showed that CTE inhibited the late stage of differentiation through diminishing expression of adipogenic transcription factors including PPARγ and C/EBPα. The inhibitory action was subsequently attenuated in downregulation of fatty acid synthase and acetyl-CoA carboxylase, causing the reduction of TG accumulation. In addition, CTE also enhanced catecholamine-induced lipolysis in adipocytes. These results suggest that CTE effectively attenuates adipogenesis by controlling cell cycle progression and downregulating adipogenic gene expression.
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Affiliation(s)
- Poramin Chayaratanasin
- Department of Pharmacology, Faculty of Veterinary Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
- Program in Veterinary Biosciences, Faculty of Veterinary Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
| | - Allen Caobi
- Department of Biological sciences, Florida International University, Miami, FL 33199, USA.
| | - Chaturong Suparpprom
- Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Naresuan University, Ta-po, Phitsanulok 65000, Thailand.
| | - Sudarat Saenset
- Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Naresuan University, Ta-po, Phitsanulok 65000, Thailand.
| | - Porntip Pasukamonset
- Department of Home Economics, Faculty of Agriculture, Kasetsart University, Bangkok 10900, Thailand.
| | - Nipattra Suanpairintr
- Department of Pharmacology, Faculty of Veterinary Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
| | | | - Sirichai Adisakwattana
- Department of Nutrition and Dietetics, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
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Jung YC, Kim HW, Min BK, Cho JY, Son HJ, Lee JY, Kim JY, Kwon SB, Li Q, Lee HW. Inhibitory Effect of Olive Leaf Extract on Obesity in High-fat Diet-induced Mice. In Vivo 2019; 33:707-715. [PMID: 31028187 PMCID: PMC6559891 DOI: 10.21873/invivo.11529] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 03/26/2019] [Accepted: 03/27/2019] [Indexed: 12/27/2022]
Abstract
BACKGROUND/AIM The rapid increase in the number of people who are overweight or obese, which increases the risk of diseases and health problems, is becoming an important issue. Herein, we investigated whether olive leaf extract (OLE) has potent anti-obesity effects in high-fat induced mouse models. MATERIALS AND METHODS C57BL/6 mice were randomized into normal control, high-fat diet (HFD), HFD with OLE, and HFD with garcinia groups and administered experimental diets for 12 weeks. Body weight and food intake were measured once per week and obesity-related biomarkers were evaluated in the serum and adipose tissue. RESULTS OLE significantly suppressed weight gain, food efficiency ratio, visceral fat accumulation, and serum lipid composition in HFD-induced mice. Furthermore, the expression of adipogenesis- and thermogenesis-related molecules was decreased in the OLE-treated group. CONCLUSION OLE prevents obesity development by regulating the expression of molecules involved in adipogenesis and thermogenesis.
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Affiliation(s)
- Yun-Chan Jung
- Institute of Research and Development, Chaon Corp., Seongnam, Republic of Korea
| | - Hyun Woo Kim
- Institute of Research and Development, Chaon Corp., Seongnam, Republic of Korea
| | - Bok Kee Min
- Nova K Health Corp., Seoul, Republic of Korea
| | | | | | | | | | | | - Qiang Li
- Institute of Research and Development, Chaon Corp., Seongnam, Republic of Korea
| | - Hee-Woo Lee
- Institute of Research and Development, Chaon Corp., Seongnam, Republic of Korea
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Chang E, Kim CY. Natural Products and Obesity: A Focus on the Regulation of Mitotic Clonal Expansion during Adipogenesis. Molecules 2019; 24:molecules24061157. [PMID: 30909556 PMCID: PMC6471203 DOI: 10.3390/molecules24061157] [Citation(s) in RCA: 118] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 03/18/2019] [Accepted: 03/18/2019] [Indexed: 01/07/2023] Open
Abstract
Obesity is recognized as a worldwide health crisis. Obesity and its associated health complications such as diabetes, dyslipidemia, hypertension, and cardiovascular diseases impose a big social and economic burden. In an effort to identify safe, efficient, and long-term effective methods to treat obesity, various natural products with potential for inhibiting adipogenesis were revealed. This review aimed to discuss the molecular mechanisms underlying adipogenesis and the inhibitory effects of various phytochemicals, including those from natural sources, on the early stage of adipogenesis. We discuss key steps (proliferation and cell cycle) and their regulators (cell-cycle regulator, transcription factors, and intracellular signaling pathways) at the early stage of adipocyte differentiation as the mechanisms responsible for obesity.
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Affiliation(s)
- Eugene Chang
- Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03760, Korea.
| | - Choon Young Kim
- Department of Food and Nutrition, Yeungnam University, Gyeongsan 38541, Gyeongbuk, Korea.
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Larussa T, Imeneo M, Luzza F. Olive Tree Biophenols in Inflammatory Bowel Disease: When Bitter is Better. Int J Mol Sci 2019; 20:ijms20061390. [PMID: 30897691 PMCID: PMC6471980 DOI: 10.3390/ijms20061390] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 03/15/2019] [Accepted: 03/15/2019] [Indexed: 12/19/2022] Open
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 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.
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Affiliation(s)
- Tiziana Larussa
- Department of Health Sciences, University of Catanzaro "Magna Graecia", Viale Europa, 88100 Catanzaro, Italy.
| | - Maria Imeneo
- Department of Health Sciences, University of Catanzaro "Magna Graecia", Viale Europa, 88100 Catanzaro, Italy.
| | - Francesco Luzza
- Department of Health Sciences, University of Catanzaro "Magna Graecia", Viale Europa, 88100 Catanzaro, Italy.
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Sabino M, Cappelli K, Capomaccio S, Pascucci L, Biasato I, Verini-Supplizi A, Valiani A, Trabalza-Marinucci M. Dietary supplementation with olive mill wastewaters induces modifications on chicken jejunum epithelial cell transcriptome and modulates jejunum morphology. BMC Genomics 2018; 19:576. [PMID: 30068314 PMCID: PMC6090849 DOI: 10.1186/s12864-018-4962-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Accepted: 07/26/2018] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND The Mediterranean diet is considered one of the healthier food habits and olive oil is one of its key components. Olive oil polyphenols are known to induce beneficial effects in several pathological conditions, such as inflammatory bowel disease, and to contrast the proliferation of cancer cells or hypercholesterolemia. Polyphenols are also present in waste products derived from the olive industry: olive mill wastewaters (OMWW) are rich in polyphenols and there is an increasing interest in using OMWW in animal nutrition. OMWW are attributed with positive effects in promoting chicken performance and the quality of food-derived products. However, a tissue-specific transcriptome target analysis of chickens fed with OMWW has never been attempted. RESULTS We explored the effect of dietary OMWW on the intestinal function in broilers. A morphological analysis of the jejunum revealed that OMWW reduced crypt depth, whereas no significant modifications were observed for villus height and the villus height/crypt depth ratio. An RNA Sequencing analysis was performed on isolated, intestinal, epithelial cells and 280 differentially expressed genes were found using a count-based approach. An enrichment analysis revealed that the majority of up regulated genes in the OMWW group were over-represented by the regulation of viral genome replication-related GO-Terms, whereas down regulated genes were mainly involved in cholesterol and lipid metabolism. CONCLUSIONS Our study showed how an industrial waste product can be recycled as a feed additive with a positive relapse. OMWW dietary supplementation can be a nutritional strategy to improve chicken performance and health, prevent intestinal damage, enhance innate immunity and regulate cholesterol metabolism and fat deposition.
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Affiliation(s)
- Marcella Sabino
- Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126 Perugia, Italy
| | - Katia Cappelli
- Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126 Perugia, Italy
| | - Stefano Capomaccio
- Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126 Perugia, Italy
| | - Luisa Pascucci
- Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126 Perugia, Italy
| | - Ilaria Biasato
- Department of Veterinary Sciences, University of Torino, Largo Paolo Braccini 2, 10095 Grugliasco, Italy
| | - Andrea Verini-Supplizi
- Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126 Perugia, Italy
| | - Andrea Valiani
- Istituto Zooprofilattico Sperimentale dell’Umbria e delle Marche, Via Gaetano Salvemini 1, 06126 Perugia, Italy
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Feng Z, Li X, Lin J, Zheng W, Hu Z, Xuan J, Ni W, Pan X. Oleuropein inhibits the IL-1β-induced expression of inflammatory mediators by suppressing the activation of NF-κB and MAPKs in human osteoarthritis chondrocytes. Food Funct 2018; 8:3737-3744. [PMID: 28952621 DOI: 10.1039/c7fo00823f] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Osteoarthritis (OA) is the most common form of joint disease and is widespread in the elderly population and is characterized by erosion of articular cartilage, subchondral bone sclerosis and synovitis. Oleuropein (OL), a secoiridoid, is considered as the most prevalent phenolic component in olive leaves and seeds, pulp and peel of unripe olives and has been shown to have potent anti-inflammatory effects. However, its effects on OA have not been clearly elucidated. This study aimed to assess the effect of OL on human OA chondrocytes. Human OA chondrocytes were pretreated with OL (10, 50 and 100 μM) for 2 h and subsequently stimulated with IL-1β for 24 h. The production of NO, PGE2, MMP-1, MMP-13, and ADAMTS-5 was evaluated by the Griess reaction and ELISA assays. The messenger RNA (mRNA) expression of COX-2, iNOS, MMP-1, MMP13, ADAMTS-5, aggrecan, and collagen-II was measured by using real-time PCR. The protein expressions of COX-2, iNOS, p65, IκB-α, JNK, p-JNK, ERK, p-ERK, p38, and p-p38 were tested by using western blot. We found that OL significantly inhibited the IL-1β-induced production of NO and PGE2; expression of COX-2, iNOS, MMP-1, MMP-13, and ADAMTS-5; and degradation of aggrecan and collagen-II. Furthermore, OL dramatically suppressed IL-1β-stimulated NF-κB and MAPK activation. Immunofluorescence staining demonstrated that OL could suppress IL-1β-induced phosphorylation of p65 nuclear translocation. These results indicate that the therapeutic effect of OL on OA is accomplished through the inhibition of both NF-κB and MAPK signaling pathways. Altogether, our findings provide the evidence to develop OL as a potential therapeutic agent for patients with OA.
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Affiliation(s)
- Zhenhua Feng
- Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China.
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Song H, Lim DY, Jung JI, Cho HJ, Park SY, Kwon GT, Kang YH, Lee KW, Choi MS, Park JHY. Dietary oleuropein inhibits tumor angiogenesis and lymphangiogenesis in the B16F10 melanoma allograft model: a mechanism for the suppression of high-fat diet-induced solid tumor growth and lymph node metastasis. Oncotarget 2018; 8:32027-32042. [PMID: 28410190 PMCID: PMC5458266 DOI: 10.18632/oncotarget.16757] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Accepted: 03/20/2017] [Indexed: 12/20/2022] Open
Abstract
Previously, we reported that high-fat-diet (HFD)-induced obesity stimulates melanoma progression in the B16F10 allograft model. In this study, we examined whether oleuropein (OL), the most abundant phenolic compound in olives, inhibits HFD-induced melanoma progression. Four-week-old male C57BL/6N mice were fed a HFD-diet with or without OL. After 16 weeks of feeding, B16F10-luc cells were subcutaneously injected and the primary tumor was resected 3 weeks later. OL suppressed HFD-induced solid tumor growth. In the tumor tissues, OL reduced HFD-induced expression of angiogenesis (CD31, VE-cadherin, VEGF-A, and VEGFR2), lymphangiogenesis (LYVE-1, VEGF-C, VEGF-D, and VEGFR3), and hypoxia (HIF-1α and GLUT-1) markers as well as HFD-induced increases in lipid vacuoles and M2 macrophages (MΦs). All animals were euthanized 2.5 weeks after tumor resection. OL suppressed HFD-induced increases in lymph node (LN) metastasis; expression of VEGF-A, VEGF-C, and VEGF-D in the LN; and M2-MΦs and the size of adipocytes in adipose tissues surrounding LNs. Co-culture results revealed that the crosstalk between B16F10s, M2-MΦs, and differentiated 3T3-L1 cells under hypoxic conditions increased the secretion of VEGF-A and -D, which stimulated tube formation and migration of endothelial cells (HUVECs) and lymphatic endothelial cells (LEC), respectively. Additionally, OL directly inhibited the differentiation of 3T3-L1 preadipocytes and tube formation by HUVECs and LECs. The overall results indicated that dietary OL inhibits lipid and M2-MΦ accumulation in HFD-fed mice, which contributes to decreases in VEGF secretion, thereby leading to inhibition of angiogenesis and lymphangiogenesis.
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Affiliation(s)
- Hyerim Song
- Department of Food Science and Nutrition, Hallym University, Chuncheon 24252, Republic of Korea
| | - Do Young Lim
- The Hormel Institute, University of Minnesota, Austin, MN 55912, USA
| | - Jae In Jung
- Division of Bio-Imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon 24341, Republic of Korea
| | - Han Jin Cho
- Department of Food Science and Nutrition, Hallym University, Chuncheon 24252, Republic of Korea.,WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 08826, Republic of Korea
| | - So Young Park
- Department of Food Science and Nutrition, Hallym University, Chuncheon 24252, Republic of Korea.,Advanced Institutes of Convergence Technology, Seoul National University, Suwon 16229, Republic of Korea
| | - Gyoo Taik Kwon
- Department of Food Science and Nutrition, Hallym University, Chuncheon 24252, Republic of Korea.,Advanced Institutes of Convergence Technology, Seoul National University, Suwon 16229, Republic of Korea.,Berry and Biofood Research Institute, Jeonbuk 56417, Republic of Korea
| | - Young-Hee Kang
- Department of Food Science and Nutrition, Hallym University, Chuncheon 24252, Republic of Korea
| | - Ki Won Lee
- WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 08826, Republic of Korea.,Advanced Institutes of Convergence Technology, Seoul National University, Suwon 16229, Republic of Korea.,Research Institute of Agriculture and Life Science, Seoul National University, Seoul 08826, Republic of Korea
| | - Myung-Sook Choi
- Department of Food Science and Nutrition, Kyungpook National University, Daegu 41566, Republic of Korea
| | - Jung Han Yoon Park
- Department of Food Science and Nutrition, Hallym University, Chuncheon 24252, Republic of Korea.,Advanced Institutes of Convergence Technology, Seoul National University, Suwon 16229, Republic of Korea.,Research Institute of Agriculture and Life Science, Seoul National University, Seoul 08826, Republic of Korea
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Lombardo L, Grasso F, Lanciano F, Loria S, Monetti E. Broad-Spectrum Health Protection of Extra Virgin Olive Oil Compounds. ACTA ACUST UNITED AC 2018. [DOI: 10.1016/b978-0-444-64057-4.00002-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/21/2023]
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Fujiwara Y, Tsukahara C, Ikeda N, Sone Y, Ishikawa T, Ichi I, Koike T, Aoki Y. Oleuropein improves insulin resistance in skeletal muscle by promoting the translocation of GLUT4. J Clin Biochem Nutr 2017; 61:196-202. [PMID: 29203961 PMCID: PMC5703779 DOI: 10.3164/jcbn.16-120] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Accepted: 03/13/2017] [Indexed: 01/05/2023] Open
Abstract
As the beneficial effects of the Mediterranean diet on human health are well established, the phenolic compounds in olive oil have been gaining interest. Oleuropein, a major phenolic compound in olives, is known to reduce the blood glucose levels in alloxan-induced diabetic rats and rabbits, however, its effect on type 2 diabetes caused by obesity is not clear. The purpose of this study is clarifying the effect of oleuropein on the glucose tolerance in skeletal muscle under the condition of lipotoxicity caused by type 2 diabetes. Oleuropein enhanced glucose uptake in C2C12 cells without insulin. Translocation of glucose transporter 4 (GLUT4) into the cell membrane was promoted by activation of adenosine monophosphate-activated protein kinase (AMPK) but not protein kinase B (Akt). Physiological concentration of oleuropein (10 µM) was sufficient to express beneficial effects on C2C12 cells. Oleuropein prevented palmitic acid-induced myocellular insulin resistance. Furthermore, in gastrocnemius muscles of mice fed a high fat diet, oleuropein also induced the GLUT4 localization into cell membrane. These results suggest the possibility of oleuropein to be effective for type 2 diabetes by reducing insulin resistance in skeletal muscles.
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Affiliation(s)
- Yoko Fujiwara
- Food and Nutritional Sciences, Graduate Course of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8601, Japan.,Institute for Human Life Innovation, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8601, Japan
| | - Chisato Tsukahara
- Food and Nutritional Sciences, Graduate Course of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8601, Japan
| | - Naoe Ikeda
- Food and Nutritional Sciences, Graduate Course of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8601, Japan
| | - Yasuko Sone
- Departments of Health and Nutrition, Takasaki University of Health and Welfare, 37-1 Nakaorui-machi, Takasaki-shi, Gunma 370-0033, Japan
| | - Tomoko Ishikawa
- Institute for Human Life Innovation, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8601, Japan
| | - Ikuyo Ichi
- Food and Nutritional Sciences, Graduate Course of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8601, Japan.,Institute for Human Life Innovation, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8601, Japan
| | - Taisuke Koike
- Eisai Food & Chemical Co., Ltd., 2-13-10 Nihonbashi, Chuo-ku, Tokyo 103-0027, Japan
| | - Yoshinori Aoki
- Eisai Food & Chemical Co., Ltd., 2-13-10 Nihonbashi, Chuo-ku, Tokyo 103-0027, Japan
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