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Li K, Ge X, Liu W, Huang L, Lv X, Tang Y, He Z, Yang Y, Chen M, Zeng J, Cheng P. Synthesis and Biological Evaluation of Quercetagetin Derivatives as the Inhibitors of Mcl-1 and Bcl-2 Against Leukemia. Int J Mol Sci 2025; 26:2727. [PMID: 40141366 PMCID: PMC11943384 DOI: 10.3390/ijms26062727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2025] [Revised: 03/10/2025] [Accepted: 03/14/2025] [Indexed: 03/28/2025] Open
Abstract
B-cell lymphoma-2 (Bcl-2) family proteins are fundamental regulators of intrinsic cell apoptosis, and overexpression of apoptotic proteins (Bcl-2 and Mcl-1) is a characteristic of many haematological malignancies. Thus, it is necessary to discover novel inhibitors to treat leukemia. In the current study, we synthesized a series of quercetagetin derivatives (compounds 2a-2t, 3a-3j and 4a-4g) and evaluated their anticancer activities on four leukemia cells (U937, K562, K562R and KG-1). Among those synthesized derivatives, compounds 2a exhibited the best antiproliferative activity (IC50 = 0.276, 0.159, 0.312 and 0.271 µM to U937, K562, K562R and KG-1, respectively). In addition, 2a induced apoptosis in K562 and markedly arrested the cell cycle G2/M phase of K562. The Western blot assay showed that 2a is a potential inhibitor that can effectively suppress the expression of Bcl-2 and Mcl-1. The molecular docking study predicted that 2a had firm interactions with the active pockets of Bcl-2 and Mcl-1. Finally, in silico pharmacokinetic evaluation of 2a indicated its potential as an anti-leukemia drug lead in the future.
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Affiliation(s)
- Kang Li
- Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China; (K.L.); (X.G.); (W.L.); (L.H.); (X.L.); (Y.T.); (Z.H.); (Y.Y.); (M.C.)
- Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China
| | - Xiaomei Ge
- Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China; (K.L.); (X.G.); (W.L.); (L.H.); (X.L.); (Y.T.); (Z.H.); (Y.Y.); (M.C.)
- Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China
| | - Wei Liu
- Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China; (K.L.); (X.G.); (W.L.); (L.H.); (X.L.); (Y.T.); (Z.H.); (Y.Y.); (M.C.)
- Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China
| | - Lei Huang
- Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China; (K.L.); (X.G.); (W.L.); (L.H.); (X.L.); (Y.T.); (Z.H.); (Y.Y.); (M.C.)
- Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China
| | - Xinye Lv
- Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China; (K.L.); (X.G.); (W.L.); (L.H.); (X.L.); (Y.T.); (Z.H.); (Y.Y.); (M.C.)
- Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China
| | - Yuhui Tang
- Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China; (K.L.); (X.G.); (W.L.); (L.H.); (X.L.); (Y.T.); (Z.H.); (Y.Y.); (M.C.)
- Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China
| | - Zhehao He
- Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China; (K.L.); (X.G.); (W.L.); (L.H.); (X.L.); (Y.T.); (Z.H.); (Y.Y.); (M.C.)
- Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China
| | - Yingxue Yang
- Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China; (K.L.); (X.G.); (W.L.); (L.H.); (X.L.); (Y.T.); (Z.H.); (Y.Y.); (M.C.)
- Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China
| | - Miaofen Chen
- Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China; (K.L.); (X.G.); (W.L.); (L.H.); (X.L.); (Y.T.); (Z.H.); (Y.Y.); (M.C.)
- Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China
| | - Jianguo Zeng
- Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China; (K.L.); (X.G.); (W.L.); (L.H.); (X.L.); (Y.T.); (Z.H.); (Y.Y.); (M.C.)
- Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China
| | - Pi Cheng
- Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China; (K.L.); (X.G.); (W.L.); (L.H.); (X.L.); (Y.T.); (Z.H.); (Y.Y.); (M.C.)
- Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China
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Huang Y, Xu B. Critical review on the intervention effects of flavonoids from cereal grains and food legumes on lipid metabolism. Food Chem 2025; 464:141790. [PMID: 39509881 DOI: 10.1016/j.foodchem.2024.141790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Revised: 09/22/2024] [Accepted: 10/24/2024] [Indexed: 11/15/2024]
Abstract
Obesity, often caused by disorders of lipid metabolism, is a global health concern. Flavonoids from staple grains and legumes are expected as a safer and more cost-effective alternative for the future development of dietary flavonoid-based anti-obesity dietary supplements or drugs. This review systematically summarized their content variation, metabolism in the human body, effects and molecular mechanisms on lipid metabolism. These flavonoids intervene in lipid metabolism by inhibiting lipogenesis, promoting lipolysis, enhancing energy metabolism, reducing appetite, suppressing inflammation, enhancing insulin sensitivity, and improving the composition of the gut microbial. Fermentation and sprouting techniques enhance flavonoid content and these beneficial effects. The multidirectional intervention of lipid metabolism is mainly through regulating AMPK signaling pathway. This study provides potential improvement for challenges of application, including addressing high extraction costs and improving bioavailability, ensuring safety, filling clinical study gaps, and investigating potential synergistic effects between flavonoids in grains and legumes, and other components.
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Affiliation(s)
- Yin Huang
- Food Science and Technology Program, Department of Life Sciences, BNU-HKBU United International College, Zhuhai, Guangdong 519087, China
| | - Baojun Xu
- Food Science and Technology Program, Department of Life Sciences, BNU-HKBU United International College, Zhuhai, Guangdong 519087, China.
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Eren E, Das J, Tollefsbol TO. Polyphenols as Immunomodulators and Epigenetic Modulators: An Analysis of Their Role in the Treatment and Prevention of Breast Cancer. Nutrients 2024; 16:4143. [PMID: 39683540 PMCID: PMC11644657 DOI: 10.3390/nu16234143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 11/26/2024] [Accepted: 11/27/2024] [Indexed: 12/18/2024] Open
Abstract
Breast cancer poses a substantial health challenge for women globally. Recently, there has been a notable increase in scholarly attention regarding polyphenols, primarily attributed to not only the adverse effects associated with conventional treatments but also their immune-preventive impacts. Polyphenols, nature-derived substances present in vegetation, including fruits and vegetables, have received considerable attention in various fields of science due to their probable wellness merits, particularly in the treatment and hindrance of cancer. This review focuses on the immunomodulatory effects of polyphenols in breast cancer, emphasizing their capacity to influence the reaction of adaptive and innate immune cells within the tumor-associated environment. Polyphenols are implicated in the modulation of inflammation, the enhancement of antioxidant defenses, the promotion of epigenetic modifications, and the support of immune functions. Additionally, these compounds have been shown to influence the activity of critical immune cells, including macrophages and T cells. By targeting pathways involved in immune evasion, polyphenols may augment the capacity of the defensive system to detect and eliminate tumors. The findings suggest that incorporating polyphenol-rich foods into the diet could offer a promising, collaborative (integrative) approach to classical breast cancer remedial procedures by regulating how the defense mechanism interacts with the disease.
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Affiliation(s)
- Esmanur Eren
- Department of Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA; (E.E.); (J.D.)
| | - Jyotirmoyee Das
- Department of Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA; (E.E.); (J.D.)
| | - Trygve O. Tollefsbol
- Department of Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA; (E.E.); (J.D.)
- Integrative Center for Aging Research, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- O’Neal Comprehensive Cancer Research, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Nutrition Obesity Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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Squires E, Walshe IH, Dodd A, Broadbelt E, Hayman O, McHugh MP, Howatson G. Acute Dosing Strategy with Vistula Tart Cherries for Recovery of Strenuous Exercise-A Feasibility Study. Nutrients 2024; 16:2709. [PMID: 39203845 PMCID: PMC11357489 DOI: 10.3390/nu16162709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 07/26/2024] [Accepted: 07/31/2024] [Indexed: 09/03/2024] Open
Abstract
Tart cherry (TC) consumption has become a popular nutritional strategy for recovery, particularly for the attenuation of markers associated with muscle damage. However, there are relatively few studies that have examined an acute dosing strategy. The aim of this pilot study was to explore the feasibility of using powdered Vistula TC for recovery following a bout of muscle-damaging exercise. Twenty-two recreationally active participants (mean ± SD age, stature, and mass were 23 ± 3 years old, 173 ± 10 cm, and 74 ± 17 kg, respectively) performed 40 (5 sets of 8 repetitions) maximal lengthening contractions of the elbow flexors. The participants were randomised to receive either a spray-dried TC extract or a calorie-matched placebo (12 TC, 10 placebo) for 4 days in total, starting on the day of exercise. Dependent measures of maximal voluntary contraction (MVC), muscle soreness (assessed via visual analogue scales; VAS), pain pressure threshold (PPT), range of motion (ROM), and upper arm limb girth were taken at baseline (pre), 24, 48, and 72 h post damaging exercise. There were significant changes over time among all the variables (MVC, VAS, PPT, ROM, and girth, p ≤ 0.014). There were no significant differences between the conditions for any of the variables (MVC, VAS, PPT, ROM, and girth, p > 0.3). The TC group did not recover at an accelerated rate compared to the placebo. This study provides initial insights into the use of powdered Vistula TC and its effect following strenuous (damaging) exercise bouts. Vistula TC did not improve recovery when taken acutely following a bout of damaging exercise to the elbow flexors.
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Affiliation(s)
- Emma Squires
- Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK; (E.S.); (I.H.W.); (M.P.M.)
| | - Ian H. Walshe
- Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK; (E.S.); (I.H.W.); (M.P.M.)
| | - Alex Dodd
- Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK; (E.S.); (I.H.W.); (M.P.M.)
| | - Edward Broadbelt
- Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK; (E.S.); (I.H.W.); (M.P.M.)
| | - Oliver Hayman
- Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK; (E.S.); (I.H.W.); (M.P.M.)
- School of Cardiovascular and Metabolic Health, BHF Glasgow Cardiovascular Research Centre, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow G11 6EW, UK
| | - Malachy P. McHugh
- Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK; (E.S.); (I.H.W.); (M.P.M.)
- Nicholas Institute of Sports Medicine and Athletic Trauma, New York, NY 10065, USA
| | - Glyn Howatson
- Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK; (E.S.); (I.H.W.); (M.P.M.)
- Water Research Group, North West University, Potchefstroom 2531, South Africa
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Xu J, Zhu X, Xing Y, Guan G, Zhang Y, Hui R, Wang X, Liu S, Pang H, Zhu L. Associations of dietary flavonoid intake with the risk of all-cause and cardiovascular mortality in adults. Clin Nutr ESPEN 2024; 62:270-277. [PMID: 38870019 DOI: 10.1016/j.clnesp.2024.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 05/29/2024] [Accepted: 06/03/2024] [Indexed: 06/15/2024]
Abstract
BACKGROUND AND AIMS Flavonoids are widely distributed polyphenolic compounds in the diet that possess various health-promoting effects. This study aimed to investigate the association between dietary flavonoid intake and all-cause and cardiovascular mortality in adults. METHODS AND RESULTS The data on the six main subclasses of flavonoids, including isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, and flavonols, were obtained from the 2007-2010 National Health and Nutrition Examination Survey (NHANES) dataset of adults. The participants were followed up until December 30, 2019. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for dietary flavonoid intake and mortality. The study included a total of 8758 adults (mean age 44.00 years; 47.40% men). A median follow-up of 10.7 years yielded 1113 all-cause deaths and 261 cardiovascular deaths were recorded. In comparison to category 1, category 4 of flavan-3-ols, flavonols, and total flavonoids were associated with lower risks of all-cause mortality, with multivariable-adjusted HRs of 0.71 (95% CI: 0.55-0.92, Ptrend = 0.021), 0.58 (95% CI: 0.45-0.74, Ptrend<0.001), and 0.63 (95% CI: 0.50-0.80, Ptrend = 0.010), respectively. Similarly, higher intake of category 4 flavonoids was associated with a reduced risk of cardiovascular mortality, with HRs of 0.68 (95% CI: 0.29-0.89, Ptrend = 0.035) for flavones, 0.41 (95% CI: 0.22-0.78, Ptrend = 0.001) for flavonols, and 0.54 (95% CI: 0.36-0.80, Ptrend = 0.021) for total flavonoids. CONCLUSION Dietary flavonoid intake is associated with all-cause and cardiovascular mortality. Increasing dietary flavonoid intake may reduce the risk of death in adults.
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Affiliation(s)
- Jing Xu
- Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, 710000, China
| | - Xu Zhu
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu, 210029, China
| | - Yujie Xing
- Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, 710000, China
| | - Gongchang Guan
- Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, 710000, China
| | - Yong Zhang
- Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, 710000, China
| | - Rutai Hui
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Xiqiang Wang
- Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, 710000, China
| | - Shasha Liu
- Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, 710000, China.
| | - Hui Pang
- Department of Cardiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, China.
| | - Ling Zhu
- Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, 710000, China; Department of Cardiology, The Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710000, China.
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Ilie EI, Popescu L, Luță EA, Biță A, Corbu AR, Mihai DP, Pogan AC, Balaci TD, Mincă A, Duțu LE, Olaru OT, Boscencu R, Gîrd CE. Phytochemical Characterization and Antioxidant Activity Evaluation for Some Plant Extracts in Conjunction with Pharmacological Mechanism Prediction: Insights into Potential Therapeutic Applications in Dyslipidemia and Obesity. Biomedicines 2024; 12:1431. [PMID: 39062004 PMCID: PMC11274650 DOI: 10.3390/biomedicines12071431] [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: 06/03/2024] [Revised: 06/21/2024] [Accepted: 06/25/2024] [Indexed: 07/28/2024] Open
Abstract
Lipid metabolism dysregulation can lead to dyslipidemia and obesity, which are major causes of cardiovascular disease and associated mortality worldwide. The purpose of the study was to obtain and characterize six plant extracts (ACE-Allii cepae extractum; RSE-Rosmarini extractum; CHE-Cichorii extractum; CE-Cynarae extractum; AGE-Apii graveolentis extractum; CGE-Crataegi extractum) as promising adjuvant therapies for the prevention and treatment of dyslipidemia and its related metabolic diseases. Phytochemical screening revealed that RSE was the richest extract in total polyphenols (39.62 ± 13.16 g tannic acid/100 g dry extract) and phenolcarboxylic acids (22.05 ± 1.31 g chlorogenic acid/100 g dry extract). Moreover, the spectrophotometric chemical profile highlighted a significant concentration of flavones for CGE (5.32 ± 0.26 g rutoside/100 g dry extract), in contrast to the other extracts. UHPLC-MS quantification detected considerable amounts of phenolic constituents, especially chlorogenic acid in CGE (187.435 ± 1.96 mg/g extract) and rosmarinic acid in RSE (317.100 ± 2.70 mg/g extract). Rosemary and hawthorn extracts showed significantly stronger free radical scavenging activity compared to the other plant extracts (p < 0.05). Pearson correlation analysis and the heatmap correlation matrix indicated significant correlations between phytochemical contents and in vitro antioxidant activities. Computational studies were performed to investigate the potential anti-obesity mechanism of the studied extracts using target prediction, homology modeling, molecular docking, and molecular dynamics approaches. Our study revealed that rosmarinic acid (RA) and chlorogenic acid (CGA) can form stable complexes with the active site of carbonic anhydrase 5A by either interacting with the zinc-bound catalytic water molecule or by directly binding Zn2+. Further studies are warranted to experimentally validate the predicted CA5A inhibitory activities of RA and CGA and to investigate the hypolipidemic and antioxidant activities of the proposed plant extracts in animal models of dyslipidemia and obesity.
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Affiliation(s)
- Elena Iuliana Ilie
- Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, Traian Vuia 6, 020956 Bucharest, Romania; (E.I.I.); (E.-A.L.); (A.C.P.); (T.D.B.); (L.E.D.); (O.T.O.); (R.B.); (C.E.G.)
| | - Liliana Popescu
- Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, Traian Vuia 6, 020956 Bucharest, Romania; (E.I.I.); (E.-A.L.); (A.C.P.); (T.D.B.); (L.E.D.); (O.T.O.); (R.B.); (C.E.G.)
| | - Emanuela-Alice Luță
- Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, Traian Vuia 6, 020956 Bucharest, Romania; (E.I.I.); (E.-A.L.); (A.C.P.); (T.D.B.); (L.E.D.); (O.T.O.); (R.B.); (C.E.G.)
| | - Andrei Biță
- Department of Pharmacognosy & Phytotherapy, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, Petru Rareș 2, 200349 Craiova, Romania;
| | - Alexandru Radu Corbu
- Department of Horticulture & Food Science, University of Craiova, AI Cuza 13, 200585 Craiova, Romania;
| | - Dragoș Paul Mihai
- Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, Traian Vuia 6, 020956 Bucharest, Romania; (E.I.I.); (E.-A.L.); (A.C.P.); (T.D.B.); (L.E.D.); (O.T.O.); (R.B.); (C.E.G.)
| | - Ana Corina Pogan
- Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, Traian Vuia 6, 020956 Bucharest, Romania; (E.I.I.); (E.-A.L.); (A.C.P.); (T.D.B.); (L.E.D.); (O.T.O.); (R.B.); (C.E.G.)
| | - Teodora Dalila Balaci
- Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, Traian Vuia 6, 020956 Bucharest, Romania; (E.I.I.); (E.-A.L.); (A.C.P.); (T.D.B.); (L.E.D.); (O.T.O.); (R.B.); (C.E.G.)
| | - Alexandru Mincă
- Department of Medical Semiology, Discipline of Internal Medicine I and Nephrology, Faculty of Medicine, University of Medicine and Pharmacy “Carol Davila”, Eroii Sanitari 8, 050474 Bucharest, Romania;
| | - Ligia Elena Duțu
- Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, Traian Vuia 6, 020956 Bucharest, Romania; (E.I.I.); (E.-A.L.); (A.C.P.); (T.D.B.); (L.E.D.); (O.T.O.); (R.B.); (C.E.G.)
| | - Octavian Tudorel Olaru
- Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, Traian Vuia 6, 020956 Bucharest, Romania; (E.I.I.); (E.-A.L.); (A.C.P.); (T.D.B.); (L.E.D.); (O.T.O.); (R.B.); (C.E.G.)
| | - Rica Boscencu
- Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, Traian Vuia 6, 020956 Bucharest, Romania; (E.I.I.); (E.-A.L.); (A.C.P.); (T.D.B.); (L.E.D.); (O.T.O.); (R.B.); (C.E.G.)
| | - Cerasela Elena Gîrd
- Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, Traian Vuia 6, 020956 Bucharest, Romania; (E.I.I.); (E.-A.L.); (A.C.P.); (T.D.B.); (L.E.D.); (O.T.O.); (R.B.); (C.E.G.)
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Zhao X, Ge W, Miao Z. Integrative metabolomic and transcriptomic analyses reveals the accumulation patterns of key metabolites associated with flavonoids and terpenoids of Gynostemma pentaphyllum (Thunb.) Makino. Sci Rep 2024; 14:8644. [PMID: 38622163 PMCID: PMC11018608 DOI: 10.1038/s41598-024-57716-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 03/21/2024] [Indexed: 04/17/2024] Open
Abstract
Gynostemma pentaphyllum (Thunb.) Makino (G. pentaphyllum) is a medicinal and edible plant with multiple functions of liver protection, anti-tumor, anti-inflammation, balancing blood sugar and blood lipids. The nutritional value of the G. pentaphyllum plant is mainly due to its rich variety of biologically active substances, such as flavonoids, terpenes and polysaccharides. In this study, we performed a comprehensive analysis combining metabolomics and root, stem and leaf transcriptomic data of G. pentaphyllum. We used transcriptomics and metabolomics data to construct a dynamic regulatory network diagram of G. pentaphyllum flavonoids and terpenoids, and screened the transcription factors involved in flavonoids and terpenoids, including basic helix-loop-helix (bHLH), myb-related, WRKY, AP2/ERF. Transcriptome analysis results showed that among the DEGs related to the synthesis of flavonoids and terpenoids, dihydroflavonol 4-reductase (DFR) and geranylgeranyl diphosphate synthases (GGPPS) were core genes. This study presents a dynamic image of gene expression in different tissues of G. pentaphyllum, elucidating the key genes and metabolites of flavonoids and terpenoids. This study is beneficial to a deeper understanding of the medicinal plants of G. pentaphyllum, and also provides a scientific basis for further regulatory mechanisms of plant natural product synthesis pathways and drug development.
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Affiliation(s)
- Xiaomeng Zhao
- School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, People's Republic of China
| | - Weiwei Ge
- School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, People's Republic of China
| | - Zhi Miao
- School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, People's Republic of China.
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Squires E, Walshe IH, Cheung W, Bowerbank SL, Dean JR, Wood J, McHugh MP, Plattner S, Howatson G. Plasma-Induced Changes in the Metabolome Following Vistula Tart Cherry Consumption. Nutrients 2024; 16:1023. [PMID: 38613057 PMCID: PMC11013268 DOI: 10.3390/nu16071023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 03/25/2024] [Accepted: 03/26/2024] [Indexed: 04/14/2024] Open
Abstract
Evidence suggests that tart cherry (TC) supplementation has beneficial effects on health indices and recovery following strenuous exercise. However, little is known about the mechanisms and how TC might modulate the human metabolome. The aim of this study was to evaluate the influence of an acute high- and low-dose of Vistula TC supplementation on the metabolomic profile in humans. In a randomised, double-blind, placebo controlled, cross-over design, 12 healthy participants (nine male and three female; mean ± SD age, stature, and mass were 29 ± 7 years old, 1.75 ± 0.1 m, and 77.3 ± 10.5 kg, respectively) visited the laboratory on three separate occasions (high dose; HI, low dose; LO, or placebo), separated by at least seven days. After an overnight fast, a baseline venous blood sample was taken, followed by consumption of a standardised breakfast and dose conditions (HI, LO, or placebo). Subsequent blood draws were taken 1, 2, 3, 5, and 8 h post consumption. Following sample preparation, an untargeted metabolomics approach was adopted, and the extracts analysed by LCMS/MS. When all time points were collated, a principal component analysis showed a significant difference between the conditions (p < 0.05), such that the placebo trial had homogeneity, and HI showed greater heterogeneity. In a sub-group analysis, cyanidine-3-O-glucoside (C3G), cyanidine-3-O-rutinoside (C3R), and vanillic acid (VA) were detected in plasma and showed significant differences (p < 0.05) following acute consumption of Vistula TC, compared to the placebo group. These results provide evidence that phenolics are bioavailable in plasma and induce shifts in the metabolome following acute Vistula TC consumption. These data could be used to inform future intervention studies where changes in physiological outcomes could be influenced by metabolomic shifts following acute supplementation.
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Affiliation(s)
- Emma Squires
- Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK; (E.S.); (I.H.W.); (W.C.); (S.L.B.); (J.R.D.); (J.W.); (M.P.M.)
| | - Ian H. Walshe
- Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK; (E.S.); (I.H.W.); (W.C.); (S.L.B.); (J.R.D.); (J.W.); (M.P.M.)
| | - William Cheung
- Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK; (E.S.); (I.H.W.); (W.C.); (S.L.B.); (J.R.D.); (J.W.); (M.P.M.)
| | - Samantha L. Bowerbank
- Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK; (E.S.); (I.H.W.); (W.C.); (S.L.B.); (J.R.D.); (J.W.); (M.P.M.)
| | - John R. Dean
- Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK; (E.S.); (I.H.W.); (W.C.); (S.L.B.); (J.R.D.); (J.W.); (M.P.M.)
| | - Jacob Wood
- Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK; (E.S.); (I.H.W.); (W.C.); (S.L.B.); (J.R.D.); (J.W.); (M.P.M.)
| | - Malachy P. McHugh
- Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK; (E.S.); (I.H.W.); (W.C.); (S.L.B.); (J.R.D.); (J.W.); (M.P.M.)
- Nicholas Institute of Sports Medicine and Athletic Trauma, Northwell Health, New York, NY 10065, USA
| | | | - Glyn Howatson
- Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK; (E.S.); (I.H.W.); (W.C.); (S.L.B.); (J.R.D.); (J.W.); (M.P.M.)
- Water Research Group, North West University, Potchefstroom 2531, South Africa
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9
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Olatoye FJ, Akindele A, Awodele O. The role of Kolaviron, a bioflavonoid from Garcinia kola, in the management of cardiovascular diseases: A systematic review. Heliyon 2024; 10:e27333. [PMID: 38449600 PMCID: PMC10915569 DOI: 10.1016/j.heliyon.2024.e27333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Revised: 02/17/2024] [Accepted: 02/28/2024] [Indexed: 03/08/2024] Open
Abstract
While the cardiovascular effects of Kolaviron (KV) and Garcinia kola (GK) are documented in the literature, a thorough search through literature revealed a fragmentation of information on the effect of KV and GK on cardiovascular diseases (CVDs). This systematic review aims to evaluate and summarize preclinical or clinical evidence on the effect of KV and GK on CVDs. Using the PRISMA guidelines, a systematic literature search was conducted in five medical databases (PubMed, Cochrane, EMBASE, CINAHL, and Web of Science). Inclusion criteria included both in vivo and in vitro studies related to CVDs. Eligible studies included those in which specific clinical parameters, CVD biomarkers, or voltage-gated channel effects were reported. The quality of the included studies was assessed using a modified Collaborative Approach to Meta-Analysis and Review of Animal Data from the Experimental Studies (CAMARADE) checklist. A total of 22 studies were included in this systematic review. The median and mean values of the included studies' quality scores were 6 and 5.864 ± 0.296, respectively. The results from the quality assessment of included studies validate their suitability, usefulness, and fit. Based on this systematic review, the effect of KV and GK on CVDs can be divided into eight emerging trends: (1) Anti-hypertensive/Blood pressure lowering effect; (2) Lipid profile improvement effect (3) Anti-atherosclerotic effect; (4) Anti-thrombotic effect; (5) Cardioprotection; (6) Vasodilatory effect; (7) Antioxidant effects; and (8) Genetic expression and therapeutic target for cardiovascular dysfunction. From this systematic review, it can be concluded that KV is helpful in managing CVD risk factors such as hypertension and high lipids/cholesterol. Several included studies in this review demonstrated the antihypertensive, lipid improvement, antioxidant, and signaling pathway modulation effects of KV. This potentially makes KV a good therapeutic target for the management of CVDs.
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Affiliation(s)
- Francis J. Olatoye
- Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, P.M.B. 12003, Lagos, Nigeria
| | - Abidemi.J. Akindele
- Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, P.M.B. 12003, Lagos, Nigeria
| | - Olufunsho Awodele
- Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, P.M.B. 12003, Lagos, Nigeria
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10
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Li Y, Wu J, Yu H, Lu X, Ni Y. Formononetin ameliorates cisplatin-induced hair cell death via activation of the PI3K/AKT-Nrf2 signaling pathway. Heliyon 2024; 10:e23750. [PMID: 38192850 PMCID: PMC10772176 DOI: 10.1016/j.heliyon.2023.e23750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 10/23/2023] [Accepted: 12/12/2023] [Indexed: 01/10/2024] Open
Abstract
Cisplatin (CDDP) stands as a highly effective chemotherapeutic agent; however, its ototoxicity remains a perplexing challenge in the field. Formononetin (FMNT), a potent flavonoid isolated from Astragalus membranaceus, displays a diverse range of promising pharmacological activities, encompassing antioxidant, anti-apoptotic, and anti-inflammatory effects. Nonetheless, the advantageous effects of FMNT on cisplatin-induced cochlear hair cell injury demand further investigation. This study aimed to assess the protective properties of FMNT against cisplatin-induced hair cell damage by conducting in vitro assays on explant-cultured cochlear hair cells. The findings revealed that FMNT exhibited a notable reduction in cisplatin-induced hair cell apoptosis. Also, FMNT effectively mitigated the accumulation of reactive oxygen species and mitochondrial damage in cochlear explants exposed to cisplatin, while also restoring the turnover of the reduced glutathione (GSH)/glutathione disulfide (GSSG) ratio. Furthermore, our study demonstrated that FMNT protects hair cells against CDDP injury through the activation of the PI3K/AKT-Nrf2 signaling pathway. Consequently, formononetin emerges as a potential therapeutic agent for the treatment of cisplatin-induced ototoxicity.
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Affiliation(s)
- Yimeng Li
- Otorhinolaryngology Department and ENT Institute of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, NHC Key Laboratory of Hearing Medicine Research, Fudan University, Shanghai 200031, People's Republic of China
| | - Jingfang Wu
- Otorhinolaryngology Department and ENT Institute of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, NHC Key Laboratory of Hearing Medicine Research, Fudan University, Shanghai 200031, People's Republic of China
| | - Huiqian Yu
- Otorhinolaryngology Department and ENT Institute of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, NHC Key Laboratory of Hearing Medicine Research, Fudan University, Shanghai 200031, People's Republic of China
| | - Xiaoling Lu
- Otorhinolaryngology Department and ENT Institute of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, NHC Key Laboratory of Hearing Medicine Research, Fudan University, Shanghai 200031, People's Republic of China
| | - Yusu Ni
- Otorhinolaryngology Department and ENT Institute of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, NHC Key Laboratory of Hearing Medicine Research, Fudan University, Shanghai 200031, People's Republic of China
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11
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Li J, Zhao R, Miao P, Xu F, Chen J, Jiang X, Hui Z, Wang L, Bai R. Discovery of anti-inflammatory natural flavonoids: Diverse scaffolds and promising leads for drug discovery. Eur J Med Chem 2023; 260:115791. [PMID: 37683361 DOI: 10.1016/j.ejmech.2023.115791] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Revised: 08/23/2023] [Accepted: 09/01/2023] [Indexed: 09/10/2023]
Abstract
Natural products have been utilized for medicinal purposes for millennia, endowing them with a rich source of chemical scaffolds and pharmacological leads for drug discovery. Among the vast array of natural products, flavonoids represent a prominent class, renowned for their diverse biological activities and promising therapeutic advantages. Notably, their anti-inflammatory properties have positioned them as promising lead compounds for developing novel drugs combating various inflammatory diseases. This review presents a comprehensive overview of flavonoids, highlighting their manifold anti-inflammatory activities and elucidating the underlying pathways in mediating inflammation. Furthermore, this review encompasses systematical classification of flavonoids, related anti-inflammatory targets, involved in vitro and in vivo test models, and detailed statistical analysis. We hope this review will provide researchers engaged in active natural products and anti-inflammatory drug discovery with practical information and potential leads.
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Affiliation(s)
- Junjie Li
- School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, PR China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, 311121, PR China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, PR China
| | - Rui Zhao
- School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, PR China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, 311121, PR China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, PR China
| | - Peiran Miao
- School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, PR China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, 311121, PR China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, PR China
| | - Fengfeng Xu
- School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, PR China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, 311121, PR China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, PR China
| | - Jiahao Chen
- School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, PR China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, 311121, PR China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, PR China
| | - Xiaoying Jiang
- School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, PR China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, 311121, PR China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, PR China
| | - Zi Hui
- School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, PR China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, 311121, PR China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, PR China.
| | - Liwei Wang
- School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, PR China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, 311121, PR China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, PR China.
| | - Renren Bai
- School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, PR China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, 311121, PR China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, PR China.
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12
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Aghababaei F, Hadidi M. Recent Advances in Potential Health Benefits of Quercetin. Pharmaceuticals (Basel) 2023; 16:1020. [PMID: 37513932 PMCID: PMC10384403 DOI: 10.3390/ph16071020] [Citation(s) in RCA: 153] [Impact Index Per Article: 76.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 07/08/2023] [Accepted: 07/13/2023] [Indexed: 07/30/2023] Open
Abstract
Quercetin, a flavonoid found in fruits and vegetables, has been a part of human diets for centuries. Its numerous health benefits, including antioxidant, antimicrobial, anti-inflammatory, antiviral, and anticancer properties, have been extensively studied. Its strong antioxidant properties enable it to scavenge free radicals, reduce oxidative stress, and protect against cellular damage. Quercetin's anti-inflammatory properties involve inhibiting the production of inflammatory cytokines and enzymes, making it a potential therapeutic agent for various inflammatory conditions. It also exhibits anticancer effects by inhibiting cancer cell proliferation and inducing apoptosis. Finally, quercetin has cardiovascular benefits such as lowering blood pressure, reducing cholesterol levels, and improving endothelial function, making it a promising candidate for preventing and treating cardiovascular diseases. This review provides an overview of the chemical structure, biological activities, and bioavailability of quercetin, as well as the different delivery systems available for quercetin. Incorporating quercetin-rich foods into the diet or taking quercetin supplements may be beneficial for maintaining good health and preventing chronic diseases. As research progresses, the future perspectives of quercetin appear promising, with potential applications in nutraceuticals, pharmaceuticals, and functional foods to promote overall well-being and disease prevention. However, further studies are needed to elucidate its mechanisms of action, optimize its bioavailability, and assess its long-term safety for widespread utilization.
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Affiliation(s)
- Fatemeh Aghababaei
- Centre d'Innovació, Recerca i Transferència en Tecnologia dels Aliments (CIRTTA), TECNIO-UAB, XIA, Departament de Ciència Animal i dels Aliments, Universitat Autònoma de Barcelona, UAB-Campus, 08193 Bellaterra, Spain
| | - Milad Hadidi
- Department of Organic Chemistry, Faculty of Chemical Sciences and Technologies, University of Castilla-La Mancha, 13071 Ciudad Real, Spain
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13
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Das A, Adhikari S, Deka D, Baildya N, Sahare P, Banerjee A, Paul S, Bisgin A, Pathak S. An Updated Review on the Role of Nanoformulated Phytochemicals in Colorectal Cancer. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59040685. [PMID: 37109643 PMCID: PMC10143464 DOI: 10.3390/medicina59040685] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 03/24/2023] [Accepted: 03/27/2023] [Indexed: 04/29/2023]
Abstract
The most common cancer-related cause of death worldwide is colorectal cancer. It is initiated with the formation of polyps, which further cause the development of colorectal cancer in multistep phases. Colorectal cancer mortality is high despite recent treatment breakthroughs and a greater understanding of its pathophysiology. Stress is one of the major causes of triggering different cellular signalling cascades inside the body and which might turn toward the development of cancer. Naturally occurring plant compounds or phytochemicals are being studied for medical purposes. Phytochemicals' benefits are being analyzed for inflammatory illnesses, liver failure, metabolic disorders, neurodegenerative disorders, and nephropathies. Cancer treatment with fewer side effects and better outcomes has been achieved by combining phytochemicals with chemotherapy. Resveratrol, curcumin, and epigallocatechin-3-gallate have been studied for their chemotherapeutic and chemopreventive potentiality, but hydrophobicity, solubility, poor bioavailability, and target selectivity limit the clinical uses of these compounds. The therapeutic potential is maximized by utilizing nanocarriers such as liposomes, micelles, nanoemulsions, and nanoparticles to increase phytochemical bioavailability and target specificity. This updated literature review discusses the clinical limitations, increased sensitivity, chemopreventive and chemotherapeutic effects, and the clinical limitations of the phytochemicals.
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Affiliation(s)
- Alakesh Das
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai 603103, India
| | - Suman Adhikari
- Department of Chemistry, Govt. Degree College, Dharmanagar 799253, India
| | - Dikshita Deka
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai 603103, India
| | | | - Padmavati Sahare
- Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM 3001, Juriquilla 76230, Querétaro, Mexico
| | - Antara Banerjee
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai 603103, India
| | - Sujay Paul
- Tecnologico de Monterrey, School of Engineering and Sciences, Campus Queretaro, San Pablo 76130, Querétaro, Mexico
| | - Atil Bisgin
- Cukurova University AGENTEM (Adana Genetic Diseases Diagnosis and Treatment Center), Medical Genetics Department of Medical Faculty, Cukurova University, Adana 01330, Turkey
- InfoGenom RD Laboratories of Cukurova Technopolis, Adana 01330, Turkey
| | - Surajit Pathak
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai 603103, India
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14
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Niu G, Jian T, Gai Y, Chen J. Microbiota and plant-derived vesicles that serve as therapeutic agents and delivery carriers to regulate metabolic syndrome. Adv Drug Deliv Rev 2023; 196:114774. [PMID: 36906231 DOI: 10.1016/j.addr.2023.114774] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 03/02/2023] [Accepted: 03/05/2023] [Indexed: 03/13/2023]
Abstract
The gut is a fundamental organ in controlling human health. Recently, researches showed that substances in the intestine can alter the course of many diseases through the intestinal epithelium, especially intestinal flora and exogenously ingested plant vesicles that can be transported over long distances to various organs. This article reviews the current knowledge on extracellular vesicles in modulating gut homeostasis, inflammatory response and numerous metabolic disease that share obesity as a co-morbidity. These complex systemic diseases that are difficult to cure, but can be managed by some bacterial and plant vesicles. Vesicles, due to their digestive stability and modifiable properties, have emerged as novel and targeted drug delivery vehicles for effective treatment of metabolic diseases.
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Affiliation(s)
- Guanting Niu
- Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China
| | - Tunyu Jian
- Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China
| | - Yanan Gai
- Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China
| | - Jian Chen
- Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
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15
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Bioactive Compounds (BACs): A Novel Approach to Treat and Prevent Cardiovascular Diseases. Curr Probl Cardiol 2023; 48:101664. [PMID: 36841315 DOI: 10.1016/j.cpcardiol.2023.101664] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Accepted: 02/17/2023] [Indexed: 02/26/2023]
Abstract
Cardiovascular diseases (CVDs) are one of the leading disorders of serious death and cause huge economic loss to patients and society. It is estimated that about 18 million people have a high death ratio due to the incidence of CVDs such as (stroke, coronary heart disease, and non-ischemic heart failure). Bioactive compounds (BACs) are healthy nutritional ingredients providing beneficial effects and nutritional value to the human body. Epidemiological studies strongly shed light on several bioactive compounds that are favorable candidates for CVDs treatment. Globally, the high risk of CVDs and related results on human body parts made them a serious scenario in all communities. In this present review, we intend to collect previously published data concerned over the years concerning green-colored foods and their BACs that aim to work in the prevention, diagnosis, and/or systematic treating CVDs. We also comprehensively discussed the oral delivery of several bioactive compounds derived from fruits and vegetables and their bioavailability and physiological effects on human health. Moreover, their important characteristics, such as anti-inflammatory, lowering blood pressure, anti-obesity, antioxidant, anti-diabetics, lipid-lowering responses, improving atherosclerosis, and cardioprotective properties, will be elaborated further. More precisely, medicinal plants' advantages and multifaceted applications have been reported in this literature to treat CVDs. To the best of our knowledge, this is our first attempt that will open a new window in the area of CVDs with the opportunity to achieve a better prognosis and effective treatment for CVDs.
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16
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Fontana G, Bruno M, Sottile F, Badalamenti N. The Chemistry and the Anti-Inflammatory Activity of Polymethoxyflavonoids from Citrus Genus. Antioxidants (Basel) 2022; 12:antiox12010023. [PMID: 36670885 PMCID: PMC9855034 DOI: 10.3390/antiox12010023] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 12/15/2022] [Accepted: 12/21/2022] [Indexed: 12/24/2022] Open
Abstract
Polymethoxyflavonoids (PMFs) are a large group of compounds belonging to the more general class of flavonoids that possess a flavan carbon framework decorated with a variable number of methoxy groups. Hydroxylated polymethoxyflavonoids (HPMFs), instead, are characterized by the presence of both hydroxyl and methoxy groups in their structural unities. Some of these compounds are the aglycone part in a glycoside structure in which the glycosidic linkage can involve the -OH at various positions. These compounds are particular to Citrus genus plants, especially in fruits, and they are present mainly in the peel. A considerable number of PMFs and HPMFs have shown promising biological activities and they are considered to be important nutraceuticals, responsible for some of the known beneficial effects on health associated with a regular consumption of Citrus fruits. Among their several actions on human health, it is notable that the relevant contribution in controlling the intracellular redox imbalance is associated with the inflammation processes. In this work, we aim to describe the status concerning the chemical identification and the anti-inflammatory activity of both PMFs and HPMFs. In particular, all of the chemical entities unambiguously identified by isolation and complete NMR analysis, and for which a biochemical evaluation on the pure compound was performed, are included in this paper.
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Affiliation(s)
- Gianfranco Fontana
- Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università Degli Studi di Palermo, Viale delle Scienze Ed. 17, 90128 Palermo, Italy
| | - Maurizio Bruno
- Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università Degli Studi di Palermo, Viale delle Scienze Ed. 17, 90128 Palermo, Italy
- Correspondence: (M.B.); (F.S.)
| | - Francesco Sottile
- Dipartimento di Architettura, Università Degli Studi di Palermo, Centro di Conservazione della Biodiversità di Interesse Agrario, Viale delle Scienze Ed. 14, 90128 Palermo, Italy
- Correspondence: (M.B.); (F.S.)
| | - Natale Badalamenti
- Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università Degli Studi di Palermo, Viale delle Scienze Ed. 17, 90128 Palermo, Italy
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17
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Lian MQ, Chng WH, Liang J, Yeo HQ, Lee CK, Belaid M, Tollemeto M, Wacker MG, Czarny B, Pastorin G. Plant-derived extracellular vesicles: Recent advancements and current challenges on their use for biomedical applications. J Extracell Vesicles 2022; 11:e12283. [PMID: 36519808 PMCID: PMC9753580 DOI: 10.1002/jev2.12283] [Citation(s) in RCA: 116] [Impact Index Per Article: 38.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 10/27/2022] [Accepted: 11/02/2022] [Indexed: 12/23/2022] Open
Abstract
Extracellular vesicles (EVs) represent a diverse class of lipid bilayer membrane vesicles released by both animal and plant cells. These ubiquitous vesicles are involved in intercellular communication and transport of various biological cargos, including proteins, lipids, and nucleic acids. In recent years, interest in plant-derived EVs has increased tremendously, as they serve as a scalable and sustainable alternative to EVs derived from mammalian sources. In vitro and in vivo findings have demonstrated that these plant-derived vesicles (PDVs) possess intrinsic therapeutic activities that can potentially treat diseases and improve human health. In addition, PDVs can also act as efficient and biocompatible drug carriers. While preclinical studies have shown promising results, there are still several challenges and knowledge gaps that have to be addressed for the successful translation of PDVs into clinical applications, especially in view of the lack of standardised protocols for material handling and PDV isolation from various plant sources. This review provides the readers with a quick overview of the current understanding and research on PDVs, critically analysing the current challenges and highlighting the immense potential of PDVs as a novel class of therapeutics to treat human diseases. It is expected that this work will guide scientists to address the knowledge gaps currently associated with PDVs and promote new advances in plant-based therapeutic solutions.
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Affiliation(s)
| | - Wei Heng Chng
- Department of PharmacyNational University of SingaporeSingaporeSingapore
- Integrative Sciences and Engineering Programme, NUS Graduate SchoolNational University of SingaporeSingaporeSingapore
| | - Jeremy Liang
- Department of ChemistryNational University of SingaporeSingaporeSingapore
| | - Hui Qing Yeo
- Department of PharmacyNational University of SingaporeSingaporeSingapore
- Cancer Science Institute of SingaporeNational University of SingaporeSingaporeSingapore
| | - Choon Keong Lee
- Department of PharmacyNational University of SingaporeSingaporeSingapore
| | - Mona Belaid
- Institute of Pharmaceutical ScienceKing's College LondonLondonUnited Kingdom
| | - Matteo Tollemeto
- Department of Health TechnologyTechnical University of DenmarkKongens LyngbyDenmark
| | | | - Bertrand Czarny
- School of Materials Science & EngineeringNanyang Technological UniversitySingaporeSingapore
| | - Giorgia Pastorin
- Department of PharmacyNational University of SingaporeSingaporeSingapore
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18
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Wang Q, Yang B, Wang N, Gu J. Tumor immunomodulatory effects of polyphenols. Front Immunol 2022; 13:1041138. [PMID: 36505462 PMCID: PMC9729837 DOI: 10.3389/fimmu.2022.1041138] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Accepted: 11/14/2022] [Indexed: 11/25/2022] Open
Abstract
Polyphenols, commonly found in various plants, have attracted enormous attention due to their potential pharmacological activity, especially antitumor activity dependent on immune function. In recent years, the development of nanomedicine can counteract the low bioavailability of polyphenols and improve the effect of tumor treatment. Among them, metal-phenolic networks (MPNs), which utilize various metal ions and phenolic ligands for coordination binding, have now become candidates for polyphenol-based nanomedicine treatment of tumors. In this mini-review, we described the classification of polyphenols and their mechanisms in antitumor immune responses, and provided suggestions for the next steps of treating tumors with polyphenols.
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Affiliation(s)
- Qin Wang
- School of Pharmacy, Southwest Minzu University, Chengdu, Sichuan, China
| | | | | | - Jian Gu
- School of Pharmacy, Southwest Minzu University, Chengdu, Sichuan, China
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19
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Ali S, Birhanu BT, Lee EB, Quah Y, Boby N, Suk K, Lee SP, Lee SJ, Park SC. Immunomodulatory effects of Bacillus subtilis-fermented soybean extract in mice. FOOD BIOTECHNOL 2022. [DOI: 10.1080/08905436.2022.2124265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Affiliation(s)
- Sekendar Ali
- Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea
- Department of Biomedical Science and Department of Pharmacology, School of Medicine, Brain Science and Engineering Institute, Kyungpook National University, Daegu, South Korea
- Department of Pharmacy, International Islamic University Chittagong, Kumira, Bangladesh
| | - Biruk Tesfaye Birhanu
- Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea
- Cardiovascular Research Institute, Kyungpook National University, Daegu, South Korea
| | - Eon-Bee Lee
- Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea
| | - Yixian Quah
- Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea
| | - Naila Boby
- Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea
| | - Kyoungho Suk
- Department of Biomedical Science and Department of Pharmacology, School of Medicine, Brain Science and Engineering Institute, Kyungpook National University, Daegu, South Korea
| | - Sam-Pin Lee
- Department of Food Science and Technology, Keimyung University, Daegu, South Korea
| | - Seung-Jin Lee
- Development and Reproductive Toxicology Research Group, Korea Institute of Toxicology, Daejeon, South Korea
| | - Seung-Chun Park
- Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea
- Cardiovascular Research Institute, Kyungpook National University, Daegu, South Korea
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20
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Ataei L, Giannaki CD, Petrou C, Aphamis G. Effect of Tribulus terrestris L. supplementation on Exercise-Induced Oxidative Stress and Delayed Onset Muscle Soreness Markers: A Pilot Study. J Diet Suppl 2022; 20:811-831. [PMID: 36073362 DOI: 10.1080/19390211.2022.2120147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
Tribulus terrestris L. contains compounds with antioxidant and anti-inflammatory properties, but its effects on exercise-induced oxidative stress and inflammatory responses are unclear. The aim of this study was to examine whether Tribulus terrestris L. supplementation can attenuate oxidative stress and inflammatory responses to acute aerobic exercise and improve DOMS. In a randomized, double-blind, crossover design study, thirteen healthy men received either a daily supplement of Tribulus terrestris L. or a placebo for 4 weeks (2-week wash-out period between trials). Before and after the supplementation periods, participants performed an exercise test to exhaustion (75% VO2max). DOMS, thigh girth, and knee joint range of motion (KJRM) were assessed before and after the exercise (2, 24, and 48 h). Blood samples were analyzed for reduced (GSH) and oxidized (GSSG) glutathione, GSH/GSSG ratio, protein carbonyls, total antioxidant capacity, creatine kinase activity, white blood cell count, and TBARS. Acute exercise to exhaustion induced inflammatory responses and changed the blood redox status in both Tribulus and Placebo groups (p < 0.050). Tribulus terrestris L. improved GSH fall (p = 0.005), GSSG rise (p = 0.001) and maintained a higher level of GSH/GSSG ratio at the 2 h point (p = 0.034). TBARS were lowered, protein carbonyls, creatine kinase activity, and white blood cell count elevation diminished significantly (p < 0.050). Tribulus terrestris L. administration did not affect DOMS, thigh girth, or KJRM (p > 0.050). 4-weeks of Tribulus terrestris L. supplementation effectively attenuates oxidative stress responses but cannot improve DOMS.
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Affiliation(s)
- Leila Ataei
- Department of Life and Health Sciences, University of Nicosia, Nicosia, Cyprus
| | | | - Christos Petrou
- Department of Life and Health Sciences, University of Nicosia, Nicosia, Cyprus
| | - George Aphamis
- Department of Life and Health Sciences, University of Nicosia, Nicosia, Cyprus
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21
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Rebelo KS, Nunez CEC, Cazarin CBB, Maróstica Júnior MR, Kristiansen K, Danneskiold-Samsøe NB. Pot-pollen supplementation reduces fasting glucose and modulates the gut microbiota in high-fat/high-sucrose fed C57BL/6 mice. Food Funct 2022; 13:3982-3992. [PMID: 35311861 DOI: 10.1039/d1fo03019a] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Pot-pollen is a mixture of pollen and nectar from flowers combined with salivary substances of stingless bees, which together are fermented inside cerumen pots. As pot-pollen is rich in polyphenols, we hypothesized that dietary ingestion could modulate obesity, glucose metabolism, and the gut microbiota in an animal model of diet-induced obesity. Male C57BL/6J mice were fed a low-fat/low-sucrose diet (LF/LS), a HF/HS diet or a HF/HS diet containing 0.1% pot-pollen (HF/HS-PP) for 12 weeks. In HF/HS-fed mice, pot-pollen supplementation decreased fasting blood glucose and increased glucose-stimulated insulin secretion without modifying weight gain, body composition, glucose tolerance, and insulin sensitivity. Intake of pot-pollen resulted in changes of the gut microbiota, including a decrease in the abundance of the Rikenellaceae RC9 gut group and Lactobacillus, and an increase in the abundance of Romboutsia. Correlations between genus abundances and metabolic changes in response to supplementation indicated that the gut microbiota contributed to the positive effects of pot-pollen ingestion on fasting glucose. Pot-pollen supplementation-associated changes in the gut microbiota composition correlated with the lowering of fasting glucose levels without modulating weight gain.
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Affiliation(s)
- Kemilla Sarmento Rebelo
- Department of Food and Nutrition, School of Food Engineering, University of Campinas, C.P. 6121, 13083-862, Campinas, SP, Brazil. .,Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen, Denmark
| | - Carla Evelyn Coimbra Nunez
- Department of Food and Nutrition, School of Food Engineering, University of Campinas, C.P. 6121, 13083-862, Campinas, SP, Brazil. .,Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen, Denmark
| | - Cinthia Baú Betim Cazarin
- Department of Food and Nutrition, School of Food Engineering, University of Campinas, C.P. 6121, 13083-862, Campinas, SP, Brazil.
| | - Mário Roberto Maróstica Júnior
- Department of Food and Nutrition, School of Food Engineering, University of Campinas, C.P. 6121, 13083-862, Campinas, SP, Brazil.
| | - Karsten Kristiansen
- Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen, Denmark
| | - Niels Banhos Danneskiold-Samsøe
- Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen, Denmark
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22
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TOKTAY E, GÜRBÜZ MA, BAL T, ÖZGÜL Ö, ERBAŞ E, UGAN RA, SELLİ J. Protective effect of daidzein on ovarian ischemia‑reperfusion injury in rats. CUKUROVA MEDICAL JOURNAL 2022. [DOI: 10.17826/cumj.993250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
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23
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Dietary Supplementation for Attenuating Exercise-Induced Muscle Damage and Delayed-Onset Muscle Soreness in Humans. Nutrients 2021; 14:nu14010070. [PMID: 35010943 PMCID: PMC8746365 DOI: 10.3390/nu14010070] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Revised: 12/17/2021] [Accepted: 12/20/2021] [Indexed: 12/12/2022] Open
Abstract
Dietary supplements are widely used as a nutritional strategy to improve and maintain performance and achieve faster recovery in sports and exercise. Exercise-induced muscle damage (EIMD) is caused by mechanical stress and subsequent inflammatory responses including reactive oxygen species and cytokine production. Therefore, dietary supplements with anti-inflammatory and antioxidant properties have the potential to prevent and reduce muscle damage and symptoms characterized by loss of muscle strength and delayed-onset muscle soreness (DOMS). However, only a few supplements are considered to be effective at present. This review focuses on the effects of dietary supplements derived from phytochemicals and listed in the International Olympic Committee consensus statement on muscle damage evaluated by blood myofiber damage markers, muscle soreness, performance, and inflammatory and oxidative stress markers. In this review, the effects of dietary supplements are also discussed in terms of study design (i.e., parallel and crossover studies), exercise model, and such subject characteristics as physical fitness level. Future perspectives and considerations for the use of dietary supplements to alleviate EIMD and DOMS are also discussed.
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24
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Rivera-Yañez CR, Ruiz-Hurtado PA, Mendoza-Ramos MI, Reyes-Reali J, García-Romo GS, Pozo-Molina G, Reséndiz-Albor AA, Nieto-Yañez O, Méndez-Cruz AR, Méndez-Catalá CF, Rivera-Yañez N. Flavonoids Present in Propolis in the Battle against Photoaging and Psoriasis. Antioxidants (Basel) 2021; 10:antiox10122014. [PMID: 34943117 PMCID: PMC8698766 DOI: 10.3390/antiox10122014] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 12/09/2021] [Accepted: 12/17/2021] [Indexed: 12/13/2022] Open
Abstract
The skin is the main external organ. It protects against different types of potentially harmful agents, such as pathogens, or physical factors, such as radiation. Skin disorders are very diverse, and some of them lack adequate and accessible treatment. The photoaging of the skin is a problem of great relevance since it is related to the development of cancer, while psoriasis is a chronic inflammatory disease that causes scaly skin lesions and deterioration of the lifestyle of people affected. These diseases affect the patient's health and quality of life, so alternatives have been sought that improve the treatment for these diseases. This review focuses on describing the properties and benefits of flavonoids from propolis against these diseases. The information collected shows that the antioxidant and anti-inflammatory properties of flavonoids play a crucial role in the control and regulation of the cellular and biochemical alterations caused by these diseases; moreover, flavones, flavonols, flavanones, flavan-3-ols, and isoflavones contained in different worldwide propolis samples are the types of flavonoids usually evaluated in both diseases. Therefore, the research carried out in the area of dermatology with bioactive compounds of different origins is of great relevance to developing preventive and therapeutic approaches.
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Affiliation(s)
- Claudia Rebeca Rivera-Yañez
- Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico;
| | - Porfirio Alonso Ruiz-Hurtado
- Laboratorio de Toxicología de Productos Naturales, Departamento de Farmacia, IPN, Escuela Nacional de Ciencias Biológicas, Av. Wilfrido Massieu, Gustavo A. Madero 07738, Mexico;
| | - María Isabel Mendoza-Ramos
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico; (M.I.M.-R.); (J.R.-R.); (G.S.G.-R.); (G.P.-M.); (O.N.-Y.); (A.R.M.-C.)
- Laboratorio de Inmunología, Unidad de Morfofisiología y Función, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico
| | - Julia Reyes-Reali
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico; (M.I.M.-R.); (J.R.-R.); (G.S.G.-R.); (G.P.-M.); (O.N.-Y.); (A.R.M.-C.)
- Laboratorio de Inmunología, Unidad de Morfofisiología y Función, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico
| | - Gina Stella García-Romo
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico; (M.I.M.-R.); (J.R.-R.); (G.S.G.-R.); (G.P.-M.); (O.N.-Y.); (A.R.M.-C.)
- Laboratorio de Inmunología, Unidad de Morfofisiología y Función, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico
| | - Glustein Pozo-Molina
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico; (M.I.M.-R.); (J.R.-R.); (G.S.G.-R.); (G.P.-M.); (O.N.-Y.); (A.R.M.-C.)
- Laboratorio de Genética y Oncología Molecular, Laboratorio 5, Edificio A4, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico
| | - Aldo Arturo Reséndiz-Albor
- Laboratorio de Inmunidad de Mucosas, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Salvador Díaz Mirón y Plan de San Luis S/N, Miguel Hidalgo, Casco de Santo Tomas, Mexico City 11340, Mexico;
| | - Oscar Nieto-Yañez
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico; (M.I.M.-R.); (J.R.-R.); (G.S.G.-R.); (G.P.-M.); (O.N.-Y.); (A.R.M.-C.)
| | - Adolfo René Méndez-Cruz
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico; (M.I.M.-R.); (J.R.-R.); (G.S.G.-R.); (G.P.-M.); (O.N.-Y.); (A.R.M.-C.)
- Laboratorio de Inmunología, Unidad de Morfofisiología y Función, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico
| | - Claudia Fabiola Méndez-Catalá
- Laboratorio de Genética y Oncología Molecular, Laboratorio 5, Edificio A4, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico
- División de Investigación y Posgrado, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico
- Correspondence: (C.F.M.-C.); (N.R.-Y.); Tel.: +52-5522-476-721 (N.R.-Y.)
| | - Nelly Rivera-Yañez
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico; (M.I.M.-R.); (J.R.-R.); (G.S.G.-R.); (G.P.-M.); (O.N.-Y.); (A.R.M.-C.)
- División de Investigación y Posgrado, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico
- Correspondence: (C.F.M.-C.); (N.R.-Y.); Tel.: +52-5522-476-721 (N.R.-Y.)
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25
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Pillai SC, Borah A, Jacob EM, Kumar DS. Nanotechnological approach to delivering nutraceuticals as promising drug candidates for the treatment of atherosclerosis. Drug Deliv 2021; 28:550-568. [PMID: 33703990 PMCID: PMC7954496 DOI: 10.1080/10717544.2021.1892241] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 02/14/2021] [Accepted: 02/15/2021] [Indexed: 12/25/2022] Open
Abstract
Atherosclerosis is Caesar's sword, which poses a huge risk to the present generation. Understanding the atherosclerotic disease cycle would allow ensuring improved diagnosis, better care, and treatment. Unfortunately, a highly effective and safe way of treating atherosclerosis in the medical community remains a continuous challenge. Conventional treatments have shown considerable success, but have some adverse effects on the human body. Natural derived medications or nutraceuticals have gained immense popularity in the treatment of atherosclerosis due to their decreased side effects and toxicity-related issues. In hindsight, the contribution of nutraceuticals in imparting enhanced clinical efficacy against atherosclerosis warrants more experimental evidence. On the other hand, nanotechnology and drug delivery systems (DDS) have revolutionized the way therapeutics are performed and researchers have been constantly exploring the positive effects that DDS brings to the field of therapeutic techniques. It could be as exciting as ever to apply nano-mediated delivery of nutraceuticals as an additional strategy to target the atherosclerotic sites boasting high therapeutic efficiency of the nutraceuticals and fewer side effects.
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Affiliation(s)
- Sindhu C. Pillai
- Bio-Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, Saitama, Japan
| | - Ankita Borah
- Bio-Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, Saitama, Japan
| | - Eden Mariam Jacob
- Bio-Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, Saitama, Japan
| | - D. Sakthi Kumar
- Bio-Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, Saitama, Japan
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26
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Al-Jumaili MHA, Al Hdeethi MKY. Study of Selected Flavonoid Structures and Their Potential Activity as Breast Anticancer Agents. Cancer Inform 2021; 20:11769351211055160. [PMID: 34803373 PMCID: PMC8597067 DOI: 10.1177/11769351211055160] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 10/02/2021] [Indexed: 12/25/2022] Open
Abstract
Flavonoids contain pharmacological effects that help to protect cells from damage. However, the anticancer activity of flavonoids is related to their modulation of signal transduction pathways within cancer cells. Natural substances such as flavonoids have immune-stimulating anti-tumor effect that could lower breast cancer risk. However, various diseases included Alzheimer’s and cancer disease are associated with flavonoids intake due to their ability as antioxidant agent to alter essential cellular enzyme’s function. Therefore, through interaction between flavonoids and Cytochrome P450 (CYP) family enzymes led to make them chemopreventive agents for breast cancer. In this analysis, the chemo-informatics properties of 5 selective flavonoid derivatives and their efficiency as anti-breast cancer drugs were evaluated. Flavonoid ligands were docked with the predicted protein, which is human placental aromatase complexes with exemestane, a breast cancer drug (3S7S). Based on various docking energies, the molecular characteristics and bioactivity score of the following components, C15H12O6 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-2,3-dihydro-4H-chromen-4-one and C15H12O5 5,8-dihydroxy-2-(4-hydroxyphenyl)-2,3-dihydro-4H-chromen-4-one showed greatest molecular properties and bioactivity docking scores of −8.633117 and −8.633117 kcal/mol respectively. Therefore, both compounds could be considered antitumor agent.
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27
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Bouhlel Chatti I, Krichen Y, Maatouk M, Lahmar A, Ghoul Mazgar S, Kammoun R, Safta Skhiri S, Chekir Ghedira L, Krifa M. Evaluation of Anticancer Potential of Flavones from Rhamnus alaternus against B16F10 Melanoma Cells. Nutr Cancer 2021; 74:2265-2275. [PMID: 34783289 DOI: 10.1080/01635581.2021.2004171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Melanoma has become an important health problem and new treatment have become an imperative medical need. Therefore, the finding and identification of natural product with less toxic effects, capable of promoting melanoma cell death have become an important goal of research in oncotherapy. In this study, we want to investigate the anticancer activity of an enriched total oligomers flavonoids (TOF) extract of R. alaternus in melanoma cells. First, TOF was exhibited to be rich in flavones. We revealed that this extract reduced proliferation and increased of sub-G1 and S phase cells built-up in B16-F10 cells in a dose-related manner. Moreover, In Vivo, TOF reduced tumor volume and weight with percentages of inhibition of 92.4% and 92.9%, respectively. R. alaternus was also found to be effective in reducing the level of pro-inflammatory cytokine IL-6 during metastasis. Level of TH1 cytokine, such as IL-2, was significantly enhanced by TOF treatment. Indeed, the histological examination of the tumor revealed the absence of mitoses and the presence of numerous melanin pigmented macrophage cells in the R. alaternus extract-treated group that could be explained by the induction of macrophage activation and by the arrest of the cell cycle in the Sub-G1 and S phases.
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Affiliation(s)
- Ines Bouhlel Chatti
- Unity of Bioactive Natural Substances and Biotechnology, Faculty of Dental Medicine, University of Monastir, Monastir, Tunisia.,Department of Biology and Geology, Higher Institute of Applied Science and Technology of Gabes, University of Gabes, Gabés, Tunisia
| | - Yosr Krichen
- Unity of Bioactive Natural Substances and Biotechnology, Faculty of Dental Medicine, University of Monastir, Monastir, Tunisia.,Pharmacognosy Laboratory, Faculty of pharmacy, University of Monastir, Monastir, Tunisia
| | - Mouna Maatouk
- Unity of Bioactive Natural Substances and Biotechnology, Faculty of Dental Medicine, University of Monastir, Monastir, Tunisia
| | - Aida Lahmar
- Unity of Bioactive Natural Substances and Biotechnology, Faculty of Dental Medicine, University of Monastir, Monastir, Tunisia
| | - Sonia Ghoul Mazgar
- ABCDF Laboratory, Faculty of Dental Medicine, University of Monastir, Monastir, Tunisia
| | - Rim Kammoun
- ABCDF Laboratory, Faculty of Dental Medicine, University of Monastir, Monastir, Tunisia
| | - Sihem Safta Skhiri
- ABCDF Laboratory, Faculty of Dental Medicine, University of Monastir, Monastir, Tunisia
| | - Leila Chekir Ghedira
- Unity of Bioactive Natural Substances and Biotechnology, Faculty of Dental Medicine, University of Monastir, Monastir, Tunisia
| | - Mounira Krifa
- Unity of Bioactive Natural Substances and Biotechnology, Faculty of Dental Medicine, University of Monastir, Monastir, Tunisia
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28
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de Araújo Esteves Duarte I, Milenkovic D, Borges TK, de Lacerda de Oliveira L, Costa AM. Brazilian passion fruit as a new healthy food: from its composition to health properties and mechanisms of action. Food Funct 2021; 12:11106-11120. [PMID: 34651638 DOI: 10.1039/d1fo01976g] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The Brazilian biodiversity is one of the largest in the world, with about 41 000 species cataloged within two global biodiversity hotspots: Atlantic Forest and Cerrado, the Brazilian savannah. Passiflora, known also as passion flowers, is a genus of which 96% of its species are distributed in the Americas, mainly Brazil and Colombia. Passion fruit extracts have a commercial value on a global scale through the pharmaceutical, nutraceutical, self-care, and food and beverage industries. Passiflora are widely studied due to their potential antioxidant, anti-inflammatory, anxiolytic, antidepressant and vascular and neuronal protective effects, probably owing to their content of polyphenols. Passiflora setacea DC is a species of wild passion fruit from the Brazilian Cerrado, rich in flavonoid C-glycosides, homoorientin, vitexin, isovitexin and orientin. Intake of these plant food bioactives has been associated with protection against chronic non-communicable diseases (CNDCs), including cardiovascular diseases, cancers, and neurodegenerative diseases. In this review, we aimed to discuss the varieties of Passiflora, their content in plant food bioactives and their potential molecular mechanisms of action in preventing or reversing CNDCs.
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Affiliation(s)
- Isabella de Araújo Esteves Duarte
- Postgraduate Program in Human Nutrition, College of Health Sciences, Campus Universitário Darcy Ribeiro, University of Brasilia, Brasília DF 70.910-900, Brazil.
| | - Dragan Milenkovic
- Unité de Nutrition Humaine, Université Clermont Auvergne, INRAE, UNH, F-63000 Clermont-Ferrand, France.,Department of Internal Medicine, Division of Cardiovascular Medicine, School of Medicine, University of California Davis, Davis, CA 95616, USA
| | - Tatiana Karla Borges
- Laboratory of Cellular Immunology, Faculty of Medicine, University of Brasilia, Brasília DF 70.910-900, Brazil
| | - Livia de Lacerda de Oliveira
- Postgraduate Program in Human Nutrition, College of Health Sciences, Campus Universitário Darcy Ribeiro, University of Brasilia, Brasília DF 70.910-900, Brazil.
| | - Ana Maria Costa
- Laboratory of Food Science, Embrapa Cerrados, Planaltina DF 73.310-970, Brazil
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29
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Natural Antioxidants from Plant Extracts in Skincare Cosmetics: Recent Applications, Challenges and Perspectives. COSMETICS 2021. [DOI: 10.3390/cosmetics8040106] [Citation(s) in RCA: 89] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
In recent years, interest in the health effects of natural antioxidants has increased due to their safety and applicability in cosmetic formulation. Nevertheless, efficacy of natural antioxidants in vivo is less documented than their prooxidant properties in vivo. Plant extracts rich in vitamins, flavonoids, and phenolic compounds can induce oxidative damage by reacting with various biomolecules while also providing antioxidant properties. Because the biological activities of natural antioxidants differ, their effectiveness for slowing the aging process remains unclear. This review article focuses on the use of natural antioxidants in skincare and the possible mechanisms underlying their desired effect, along with recent applications in skincare formulation and their limitations.
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Bielory L, Tabliago NRA. Flavonoid and cannabinoid impact on the ocular surface. Curr Opin Allergy Clin Immunol 2021; 20:482-492. [PMID: 32796166 DOI: 10.1097/aci.0000000000000673] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
PURPOSE OF REVIEW To evaluate the impact of flavonoids and cannabinoids as anti-inflammatory and antiallergic treatments on the anterior surface of the eye. RECENT FINDINGS Allergic conjunctivitis and dry eye syndrome are common ocular surface diseases that have been treated with traditional pharmacological measures, e.g. corticosteroids, antihistamines. Given the side-effect profiles of these medications and the growing interest in complementary treatment modalities as part of integrative medical interventions, well known flavonoids, such as quercetin and catechin, are under investigation for topical and systemic application methods for relief. As flavonoid derivatives, pycnogenol and epigallocatechin gallate have alleviated dry eye symptoms, including lacrimal gland inflammation, tear secretion, and the stability of the tear film. Research on ocular cannabinoid receptors and response to synthetic cannabinoids are also being considered for therapy of anterior ocular disorders. The expansion of herbal formulations provides a framework for future treatment regimens for ocular surface disorders. SUMMARY Flavonoids and cannabinoids show promise as potential complementary treatment for allergic diseases because of their anti-inflammatory and antiallergic properties. Several studies implementing ocular and systemic application of these compounds show potential in becoming adjuvant treatment strategies for improving quality of life while also managing ocular surface disease processes.
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Affiliation(s)
- Leonard Bielory
- Professor of Medicine, Allergy, Immunology and Ophthalmology, Hackensack Meridian School of Medicine, Springfield
| | - Nikko Rowe A Tabliago
- Overlook Medical Center, Atlantic Health System, St. George's University Medical School, Summit, New Jersey, USA
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Stromsnes K, Correas AG, Lehmann J, Gambini J, Olaso-Gonzalez G. Anti-Inflammatory Properties of Diet: Role in Healthy Aging. Biomedicines 2021; 9:922. [PMID: 34440125 PMCID: PMC8389628 DOI: 10.3390/biomedicines9080922] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 07/22/2021] [Accepted: 07/26/2021] [Indexed: 12/18/2022] Open
Abstract
Inflammation is a physiological process involved in the defenses of the body and the repair of tissues. It is acutely activated by infections, trauma, toxins, or allergic reactions. However, if it becomes chronic, inflammation can end up stimulating the development of diseases such as cardiovascular disease, autoimmune disease, neurological disease, or cancer. Additionally, during aging, inflammation becomes increasingly more chronic. Furthermore, we found that certain foods, such as saturated fats, have pro-inflammatory activity. Taking this into account, in this review we have discussed different diets with possible anti-inflammatory activity, the commonly ingested components of each diet and their active compounds. In addition, we have proposed some dietary guidelines, as well as a list of compounds present in foods with anti-inflammatory activity, outlining how to combine them to achieve optimal anti-inflammatory effects. Therefore, we can conclude that the compounds in our diet with anti-inflammatory activity could help alleviate the inflammatory processes derived from diseases and unhealthy diets, and thereby promote healthy aging.
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Affiliation(s)
- Kristine Stromsnes
- Freshage Research Group, Department of Physiology, Faculty of Medicine, Insitute of Health Research-INCLIVA, University of Valencia and CIBERFES, Avda. Blasco Ibañez, 15, 46010 Valencia, Spain; (K.S.); (A.G.C.); (G.O.-G.)
| | - Angela G. Correas
- Freshage Research Group, Department of Physiology, Faculty of Medicine, Insitute of Health Research-INCLIVA, University of Valencia and CIBERFES, Avda. Blasco Ibañez, 15, 46010 Valencia, Spain; (K.S.); (A.G.C.); (G.O.-G.)
| | - Jenny Lehmann
- Department of Molecular Toxicology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany;
- Institute of Nutritional Science, University of Potsdam, 14558 Nuthetal, Germany
| | - Juan Gambini
- Freshage Research Group, Department of Physiology, Faculty of Medicine, Insitute of Health Research-INCLIVA, University of Valencia and CIBERFES, Avda. Blasco Ibañez, 15, 46010 Valencia, Spain; (K.S.); (A.G.C.); (G.O.-G.)
| | - Gloria Olaso-Gonzalez
- Freshage Research Group, Department of Physiology, Faculty of Medicine, Insitute of Health Research-INCLIVA, University of Valencia and CIBERFES, Avda. Blasco Ibañez, 15, 46010 Valencia, Spain; (K.S.); (A.G.C.); (G.O.-G.)
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Messeha SS, Zarmouh NO, Soliman KFA. Polyphenols Modulating Effects of PD-L1/PD-1 Checkpoint and EMT-Mediated PD-L1 Overexpression in Breast Cancer. Nutrients 2021; 13:nu13051718. [PMID: 34069461 PMCID: PMC8159140 DOI: 10.3390/nu13051718] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 05/11/2021] [Accepted: 05/17/2021] [Indexed: 12/12/2022] Open
Abstract
Investigating dietary polyphenolic compounds as antitumor agents are rising due to the growing evidence of the close association between immunity and cancer. Cancer cells elude immune surveillance for enhancing their progression and metastasis utilizing various mechanisms. These mechanisms include the upregulation of programmed death-ligand 1 (PD-L1) expression and Epithelial-to-Mesenchymal Transition (EMT) cell phenotype activation. In addition to its role in stimulating normal embryonic development, EMT has been identified as a critical driver in various aspects of cancer pathology, including carcinogenesis, metastasis, and drug resistance. Furthermore, EMT conversion to another phenotype, Mesenchymal-to-Epithelial Transition (MET), is crucial in developing cancer metastasis. A central mechanism in the upregulation of PD-L1 expression in various cancer types is EMT signaling activation. In breast cancer (BC) cells, the upregulated level of PD-L1 has become a critical target in cancer therapy. Various signal transduction pathways are involved in EMT-mediated PD-L1 checkpoint overexpression. Three main groups are considered potential targets in EMT development; the effectors (E-cadherin and Vimentin), the regulators (Zeb, Twist, and Snail), and the inducers that include members of the transforming growth factor-beta (TGF-β). Meanwhile, the correlation between consuming flavonoid-rich food and the lower risk of cancers has been demonstrated. In BC, polyphenols were found to downregulate PD-L1 expression. This review highlights the effects of polyphenols on the EMT process by inhibiting mesenchymal proteins and upregulating the epithelial phenotype. This multifunctional mechanism could hold promises in the prevention and treating breast cancer.
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Affiliation(s)
- Samia S. Messeha
- Division of Pharmaceutical Sciences, College of Pharmacy & Pharmaceutical Sciences, Institute of Public Health Florida A&M University, Tallahassee, FL 32307, USA;
| | - Najla O. Zarmouh
- Faculty of Medical Technology-Misrata, Libyan National Board for Technical & Vocational Education, Misrata LY72, Libya;
| | - Karam F. A. Soliman
- Division of Pharmaceutical Sciences, College of Pharmacy & Pharmaceutical Sciences, Institute of Public Health Florida A&M University, Tallahassee, FL 32307, USA;
- Correspondence: ; Tel.: +1-850-599-3306; Fax: +1-850-599-3667
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Modulation of α-synuclein fibrillation by plant metabolites, daidzein, fisetin and scopoletin under physiological conditions. Int J Biol Macromol 2021; 182:1278-1291. [PMID: 33991558 DOI: 10.1016/j.ijbiomac.2021.05.071] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 04/01/2021] [Accepted: 05/10/2021] [Indexed: 12/11/2022]
Abstract
The aggregation of α-synuclein is linked to neurological disorders, and of these, Parkinson's disease (PD) is among the most widely studied. In this background, we have investigated here the effects of three α, β-unsaturated carbonyl based plant metabolites, daidzein, fisetin and scopoletin on α-Syn aggregation. The ThT and light scattering kinetics studies establish that these compounds have ability to inhibit α-Syn fibrillation to different extents; this is confirmed by TEM studies. It is pertinent to note here that daidzein and scopoletin have been predicted to be able to cross the blood brain barrier. ANS binding assays demonstrate that the compounds interfere in the hydrophobic interactions. The tyrosine quenching, molecular docking and MD simulation studies showed that the compounds bind with α-Syn and provide structural rigidity which delays onset of structural transitions, which is confirmed by CD spectroscopy. The results obtained here throw light on the mechanisms underlying inhibition of α-Syn fibrillation by these compounds. Thus, the current work has significant therapeutic implications for identifying plant based potent therapeutic molecules for PD and other synucleinopathies, an area which needs extensive exploration.
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The Anticancer Effects of Flavonoids through miRNAs Modulations in Triple-Negative Breast Cancer. Nutrients 2021; 13:nu13041212. [PMID: 33916931 PMCID: PMC8067583 DOI: 10.3390/nu13041212] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 03/31/2021] [Accepted: 04/02/2021] [Indexed: 12/31/2022] Open
Abstract
Triple- negative breast cancer (TNBC) incidence rate has regularly risen over the last decades and is expected to increase in the future. Finding novel treatment options with minimum or no toxicity is of great importance in treating or preventing TNBC. Flavonoids are new attractive molecules that might fulfill this promising therapeutic option. Flavonoids have shown many biological activities, including antioxidant, anti-inflammatory, and anticancer effects. In addition to their anticancer effects by arresting the cell cycle, inducing apoptosis, and suppressing cancer cell proliferation, flavonoids can modulate non-coding microRNAs (miRNAs) function. Several preclinical and epidemiological studies indicate the possible therapeutic potential of these compounds. Flavonoids display a unique ability to change miRNAs' levels via different mechanisms, either by suppressing oncogenic miRNAs or activating oncosuppressor miRNAs or affecting transcriptional, epigenetic miRNA processing in TNBC. Flavonoids are not only involved in the regulation of miRNA-mediated cancer initiation, growth, proliferation, differentiation, invasion, metastasis, and epithelial-to-mesenchymal transition (EMT), but also control miRNAs-mediated biological processes that significantly impact TNBC, such as cell cycle, immune system, mitochondrial dysregulation, modulating signaling pathways, inflammation, and angiogenesis. In this review, we highlighted the role of miRNAs in TNBC cancer progression and the effect of flavonoids on miRNA regulation, emphasizing their anticipated role in the prevention and treatment of TNBC.
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Abebe MS, Asres K, Bekuretsion Y, Abebe A, Bikila D, Seyoum G. Sub-chronic toxicity of ethanol leaf extract of Syzygium guineense on the biochemical parameters and histopathology of liver and kidney in the rats. Toxicol Rep 2021; 8:822-828. [PMID: 33868962 PMCID: PMC8044796 DOI: 10.1016/j.toxrep.2021.03.032] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 03/28/2021] [Accepted: 03/31/2021] [Indexed: 11/29/2022] Open
Abstract
Long-term use of Syzygium guineense leaf extract reduced the food intake and weight gain in rats. The serum level of liver and kidney enzymes of rats was increased by the treatment of high dose of Syzygium guineense leaf. Use of Syzygium guineense leaf extract showed hypoglycemic effect in rats. Background Syzygium guineense Wall. leaf is being used as a traditional medicine against hypertension and diabetes mellitus. Unlike its efficacy, the safety profile of this plant upon long-term administration has not been investigated yet. Therefore, this study investigated the sub-chronic toxicity of S. guineense leaves in rats. Methods Wistar albino rats, 10/sex/group were randomly assigned into four groups. Group I-III respectively received 250, 500, and 1000 mg/kg of body weight of 70 % ethanol extract ofS. guineense leaves for 90 consecutive days. Group IV (control) received distilled water. Throughout the experiment, clinical observations were carried out, food intake and weight of the rats also were measured. Finally, different biochemical parameters, organ weight, and histopathology of liver and kidneys were evaluated. Results Administration of 70 % ethanol extract ofS. guineense leaves decreased food intake and body weight gain of the test animals. Rats treated with 1000 mg/kg of S. guineense extract showed significantly increased serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels. Serum urea levels also increased in female rats treated with 500 and 1000 mg/kg body weight of S. guineense. Moreover, the blood glucose level of rats treated with 1000 mg/kg body weight was significantly decreased compared to the control group. However, the histology of the liver and kidneys were not significantly altered by any of the doses administered. Conclusion Administration ofS. guineense in rats at a dose of 1000 mg/kg body weight affected the food consumption, weight gain, and serum levels of liver and kidney enzymes suggesting that S. guineense intake at high doses may be toxic. Therefore, liberal consumption of S. guineense leaves should be taken curiously and cautiously.
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Key Words
- ALP, alkaline phosphatase
- ALT, alanine aminotransferase
- ANOVA, analysis of variance
- AST, aspartate aminotransferase
- Biochemical profile
- DPX, Dibutylphthalate Polystyrene Xylene
- EPHI, Ethiopian Public Health Institute
- H & E, hematoxylin and eosin
- IRB, institutional review board
- Kidney
- Liver
- OECD, Organization for Economic Co-operation and Development
- Rats
- SDM, standard deviation of mean SPSS: statistical package for social science
- Sub-chronic toxicity
- Syzygium guineense
- TMMRD, Traditional and Modern Medicine Research Directorate
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Affiliation(s)
- Melese Shenkut Abebe
- Department of Anatomy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Kaleab Asres
- Department Pharmaceutical Chemistry and Pharmacognosy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Yonas Bekuretsion
- Department of Pathology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Abiy Abebe
- Traditional and Modern Medicine Research Directorate, Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | - Demiraw Bikila
- National Clinical Chemistry Reference Laboratory, Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | - Girma Seyoum
- Department of Anatomy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
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Ni K, Guo J, Bu B, Pan Y, Li J, Liu L, Luo M, Deng L. Naringin as a plant-derived bitter tastant promotes proliferation of cultured human airway epithelial cells via activation of TAS2R signaling. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 84:153491. [PMID: 33601237 DOI: 10.1016/j.phymed.2021.153491] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 01/29/2021] [Accepted: 01/29/2021] [Indexed: 06/12/2023]
Abstract
BACKGROUND Bitter tastants can activate bitter taste receptors (TAS2Rs) and thus initiate relaxation of airway smooth muscle cells (ASMCs), which have great potential in the development of novel bronchodilator drugs for asthma therapy. However, the canonical bitter substance, denatonium is known to induce apoptosis of airway epithelial cells (AECs), indicating that other bitter tastants may also impair the epithelial integrity to prevent hazardous particulate matters such as coronaviruses. Therefore, any bitter tastants intended for treating airway disease should be carefully evaluated for potential toxicity to AECs. HYPOTHESIS/PURPOSE Considering the vast diversity of bitter tastants in nature and different types of TAS2Rs expressed in airway cells, we hypothesized that there must be some natural bitter tastants to be not only potent in inducing relaxation of ASMCs but also unharmful to AECs. STUDY DESIGN AND METHODS Here we evaluated a group of bitter flavonoids that are derived from fruits and commonly used in traditional herbal medicine, including apigenin, hesperetin, kaempferol, naringenin, quercetin, and naringin, for their effects on the proliferation of human airway epithelial-like (16HBE14o-, BEAS-2B, and A549) cells cultured in vitro. Cell proliferation and associated signaling pathways were assessed by cell counting, ATP assay, cell cycling assay, quantitative RT-PCR, Fluo-4 labeling, and fluorescence resonance energy transfer, respectively. RESULTS The results show that five of the six tested bitter tastants inhibited, but only naringin promoted the proliferation of the 16HBE14o-, BEAS-2B, and A549 cells at the dose of a few hundred micromoles. Furthermore, the naringin-promoted proliferation of the 16HBE14o- cells was associated with enhanced cell cycle progression, mRNA expression of cyclin E, and evoked calcium signaling/ERK signaling, which were all attenuated by inhibition of the TAS2R signaling pathways with specific blockers. CONCLUSION These findings indicate that although the majority of the bitter flavonoids may inhibit the proliferation of AECs, naringin emerged as one to promote the proliferation of AECs via cell cycle progression and TAS2R-activated intracellular signaling. It suggests that naringin and not a few other bitter tastants can be proven with nontoxicity to the airway epithelial structure and function, which provides further confidence in the development of safe and effective TAS2R-based bronchodilators for asthma therapy.
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Affiliation(s)
- Kai Ni
- Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu, China
| | - Jia Guo
- Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu, China
| | - Bing Bu
- Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu, China
| | - Yan Pan
- Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu, China
| | - Jingjing Li
- Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu, China
| | - Lei Liu
- Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu, China
| | - Mingzhi Luo
- Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu, China.
| | - Linhong Deng
- Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu, China.
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Bai A, Chen A, Chen W, Luo X, Liu S, Zhang M, Liu Y, Zhang D. Study on degradation behaviour, residue distribution, and dietary risk assessment of propiconazole in celery and onion under field application. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2021; 101:1998-2005. [PMID: 32949153 DOI: 10.1002/jsfa.10817] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 08/25/2020] [Accepted: 09/19/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND Propiconazole is widely used to control fungal diseases in field crops, including celery and onion. The potential risk to the environment and human health has aroused much public concern. Therefore, it is significant to investigate the degradation behaviour, residue distribution, and dietary risk assessment of propiconazole in celery and onion. RESULTS A sensitive analytical method for determination of propiconazole residue in celery and onion was established and validated through high-performance liquid chromatography tandem mass spectrometry. The average recovery rate of propiconazole ranged from 85.7% to 101.8%, with a relative standard deviation of 2.1-6.3%. For the dissipation kinetics, the data showed that propiconazole in celery and onion was degraded, with half-lives of 6.1-6.2 days and 8.7-8.8 days respectively. In the terminal residue experiments, the residues of propiconazole were below 4.66 mg kg-1 in celery after application two or three times and were below 0.029 mg kg-1 in onion after application of three or four times with an interval of 14 days under the designed dosages. The chronic and acute dietary exposure assessments for propiconazole were valued by risk quotient, with all values being lower than 100%. CONCLUSION Propiconazole in celery and onion was rapidly degraded following first-order kinetics models. The dietary risk of propiconazole through celery or onion was negligible to consumers. The study not only offers a valuable reference for reasonable usage of propiconazole on celery and onion, but also facilitates the establishment of maximum residue limits in China. © 2020 Society of Chemical Industry.
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Affiliation(s)
- Aijuan Bai
- Longping Branch, Graduate School of Hunan University, Changsha, 410125, China
- Hunan Plant Protection Institute, Hunan Academy of Agricultural Science, Changsha, 410125, China
| | - Ang Chen
- Hunan Plant Protection Institute, Hunan Academy of Agricultural Science, Changsha, 410125, China
| | - Wuying Chen
- Hunan Plant Protection Institute, Hunan Academy of Agricultural Science, Changsha, 410125, China
| | - Xiangwen Luo
- Hunan Plant Protection Institute, Hunan Academy of Agricultural Science, Changsha, 410125, China
| | - Shaowen Liu
- Hunan Institute of Agricultural Environment and Ecology, Hunan Academy of Agricultural Science, Changsha, 410125, China
| | - Min Zhang
- Hunan Plant Protection Institute, Hunan Academy of Agricultural Science, Changsha, 410125, China
| | - Yong Liu
- Longping Branch, Graduate School of Hunan University, Changsha, 410125, China
- Hunan Plant Protection Institute, Hunan Academy of Agricultural Science, Changsha, 410125, China
| | - Deyong Zhang
- Longping Branch, Graduate School of Hunan University, Changsha, 410125, China
- Hunan Plant Protection Institute, Hunan Academy of Agricultural Science, Changsha, 410125, China
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Jantan I, Haque MA, Arshad L, Harikrishnan H, Septama AW, Mohamed-Hussein ZA. Dietary polyphenols suppress chronic inflammation by modulation of multiple inflammation-associated cell signaling pathways. J Nutr Biochem 2021; 93:108634. [PMID: 33794330 DOI: 10.1016/j.jnutbio.2021.108634] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 01/20/2021] [Accepted: 03/10/2021] [Indexed: 02/06/2023]
Abstract
The high failure rate of the reductionist approach to discover effective and safe drugs to treat chronic inflammatory diseases has led scientists to seek alternative ways. Recently, targeting cell signaling pathways has been utilized as an innovative approach to discover drug leads from natural products. Cell signaling mechanisms have been identified playing key role in diverse diseases by inducing proliferation, cell survival and apoptosis. Phytochemicals are known to be able to modulate the cellular and molecular networks which are associated to chronic diseases including cancer-associated inflammation. In this review, the roles of dietary polyphenols (apigenin, kaempferol, quercetin, curcumin, genistein, isoliquiritigenin, resveratrol and gallic acid) in modulating multiple inflammation-associated cell signaling networks are deliberated. Scientific databases on suppressive effects of the polyphenols on chronic inflammation via modulation of the pathways especially in the recent five years are gathered and critically analyzed. The polyphenols are able to modulate several inflammation-associated cell signaling pathways, namely nuclear factor-kappa β, mitogen activated protein kinases, Wnt/β-catenin and phosphatidylinositol 3-kinase and protein kinase B via selective actions on various components of the networks. The suppressive effects of the polyphenols on the multiple cell signaling pathways reveal their potential use in prevention and treatment of chronic inflammatory disorders. Understanding the mechanistic effects involved in modulation of the signaling pathways by the polyphenols is necessary for lead identification and development of future functional foods for prevention and treatment of chronic inflammatory diseases.
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Affiliation(s)
- Ibrahim Jantan
- Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, UKM Bangi, Selangor, Malaysia.
| | - Md Areeful Haque
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, Bangladesh
| | - Laiba Arshad
- Department of Pharmacy, Forman Christian College (A Chartered University), Lahore, Pakistan
| | - Hemavathy Harikrishnan
- Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Abdi Wira Septama
- Research Center for Chemistry, Indonesian Institute of Sciences, Kawasan PUSPIPTEK Serpong, Tangerang Selatan, Banten, Indonesia
| | - Zeti-Azura Mohamed-Hussein
- Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, UKM Bangi, Selangor, Malaysia; Department of Applied Physics, Faculty of Science & Technology, Universiti Kebangsaan Malaysia, UKM Bangi, Selangor
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Choi MH, Lee MY, Yang SH, Shin HJ, Jeon YJ. Hydrophobic Fractions of Triticum aestivum L. Extracts Contain Polyphenols and Alleviate Inflammation by Regulating Nuclear Factor-kappa B. BIOTECHNOL BIOPROC E 2021. [DOI: 10.1007/s12257-020-0352-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Tart Cherry Supplementation and Recovery From Strenuous Exercise: A Systematic Review and Meta-Analysis. Int J Sport Nutr Exerc Metab 2021; 31:154-167. [PMID: 33440334 DOI: 10.1123/ijsnem.2020-0145] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Revised: 09/16/2020] [Accepted: 09/30/2020] [Indexed: 11/18/2022]
Abstract
The aim of this study was to determine the efficacy of tart cherry (TC) supplementation on recovery following strenuous exercise. A systematic review and meta-analysis were conducted using studies investigating TC supplementation on measures of muscle soreness, muscular strength, muscular power, creatine kinase, C-reactive protein, Interleukin-6, and tumor necrosis factor alpha. A literature search ending in July 2020 was conducted in three databases (SPORTDiscus, Web of Science, and PubMed). Data from 14 studies were extracted and pooled for analysis. Tart cherry supplementation had a small beneficial effect in reducing muscle soreness (effect size [ES] = -0.44, 95% confidence interval [CI] [-0.87, -0.02]). A moderate beneficial effect was observed for recovery of muscular strength (ES = -0.78, 95% CI [-1.11, -0.46]). A moderate effect was observed for muscular power (ES = -0.53, 95% CI [-0.77, -0.29]); a further subgroup analysis on this variable indicated a large effect of TC supplementation on recovery of jump height (ES = -0.82, 95% CI [-1.18, -0.45]) and a small significant effect of supplementation on sprint time (ES = -0.32, 95% CI [-0.60, -0.04]). A small effect was observed for both C-reactive protein (ES = -0.46, 95% CI [-0.93, -0.00]) and Interleukin-6 (ES = -0.35, 95% CI [-0.68, -0.02]. No significant effects were observed for creatine kinase and tumor necrosis factor alpha. These results indicate that the consumption of a TC supplement can aid aspects of recovery from strenuous exercise.
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Chen Y, Yao L, Pan W, Guo B, Lin S, Wei Y. An integrated analysis of metabolomic and transcriptomic profiles reveals flavonoid metabolic differences between Anoectochilus roxburghii and Anoectochilus formosanus. Process Biochem 2021. [DOI: 10.1016/j.procbio.2020.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Kianian F, Marefati N, Boskabady M, Ghasemi SZ, Boskabady MH. Pharmacological Properties of Allium cepa, Preclinical and Clinical Evidences; A Review. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH : IJPR 2021; 20:107-134. [PMID: 34567150 PMCID: PMC8457748 DOI: 10.22037/ijpr.2020.112781.13946] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Onion or Allium cepa (A. cepa) is one of the most important condiment plants grown and consumed all over the world. This plant has various therapeutic effects attributed to its constituents, such as quercetin, thiosulphinates and phenolic acids. In the present article, various pharmacological and therapeutic effects of A. cepa were reviewed. Different online databases using keywords such as onion, A. cepa, therapeutic effects, and pharmacological effects until the end of December 2019 were searched for this purpose. Onion has been suggested to be effective in treating a broad range of disorders, including asthma, inflammatory disorders, dysentery, wounds, scars, keloids and pain. In addition, different studies have demonstrated that onion possesses numerous pharmacological properties, including anti-cancer, anti-diabetic and anti-platelet properties as well as the effect on bone, cardiovascular, gastrointestinal, nervous, respiratory, and urogenital systems effects such as anti-osteoporosis, anti-hypertensive, antispasmodic, anti-diarrheal, neuro-protective, anti-asthmatic and diuretic effects. The present review provides detailed the various pharmacological properties of onion and its constituents and possible underlying mechanisms. The results of multiple studies suggested the therapeutic effect of onion on a wide range of disorders.
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Affiliation(s)
- Farzaneh Kianian
- Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
- F. K. and N. M. contributed equally to this work
| | - Narges Marefati
- Department of Physiology and Medical Physics, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran.
- F. K. and N. M. contributed equally to this work
| | - Marzie Boskabady
- Dental Materials Research Center and Department of Pediatric Dentistry, School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Seyyedeh Zahra Ghasemi
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Mohammad Hosein Boskabady
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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Shiwakoti S, Adhikari D, Lee JP, Kang KW, Lee IS, Kim HJ, Oak MH. Prevention of Fine Dust-Induced Vascular Senescence by Humulus lupulus Extract and Its Major Bioactive Compounds. Antioxidants (Basel) 2020; 9:E1243. [PMID: 33297587 PMCID: PMC7762380 DOI: 10.3390/antiox9121243] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 11/30/2020] [Accepted: 12/03/2020] [Indexed: 12/23/2022] Open
Abstract
Both short- and long-term exposure to fine dust (FD) from air pollution has been linked to various cardiovascular diseases (CVDs). Endothelial cell (EC) senescence is an important risk factor for CVDs, and recent evidence suggests that FD-induced premature EC senescence increases oxidative stress levels. Hop plant (Humulus lupulus) is a very rich source of polyphenols known to have nutritional and therapeutic properties, including antioxidant behavior. The aims of this study were to evaluate whether Humulus lupulus extract prevents FD-induced vascular senescence and dysfunction and, if so, to characterize the underlying mechanisms and active components. Porcine coronary arteries and endothelial cells were treated with FD in the presence or absence of hop extract (HOP), and the senescence-associated-beta galactosidase (SA-β-gal) activity, cell-cycle progression, expression of senescence markers, oxidative stress level, and vascular function were evaluated. Results indicated that HOP inhibited FD-induced SA-β-gal activity, cell-cycle arrest, and oxidative stress, suggesting that HOP prevents premature induction of senescence by FD. HOP also ameliorated FD-induced vascular dysfunction. Additionally, xanthohumol (XN) and isoxanthohumol (IX) were found to produce the protective effects of HOP. Treatment with HOP and its primary active components XN and IX downregulated the expression of p22phox, p53, and angiotensin type 1 receptor, which all are known FD-induced redox-sensitive EC senescence inducers. Taken together, HOP and its active components protect against FD-induced endothelial senescence most likely via antioxidant activity and may be a potential therapeutic agent for preventing and/or treating air-pollution-associated CVDs.
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Affiliation(s)
- Saugat Shiwakoti
- College of Pharmacy, Mokpo National University, Jeonnam, Muan-gun 58554, Korea; (S.S.); (D.A.); (J.P.L.)
| | - Deepak Adhikari
- College of Pharmacy, Mokpo National University, Jeonnam, Muan-gun 58554, Korea; (S.S.); (D.A.); (J.P.L.)
| | - Jeong Pyo Lee
- College of Pharmacy, Mokpo National University, Jeonnam, Muan-gun 58554, Korea; (S.S.); (D.A.); (J.P.L.)
| | - Ki-Woon Kang
- Division of Cardiology, Eulji University Hospital, Eulji University School of Medicine, Daejeon 34824, Korea;
| | - Ik-Soo Lee
- College of Pharmacy, Chonnam National University, Gwangju 61186, Korea;
| | - Hyun Jung Kim
- College of Pharmacy, Mokpo National University, Jeonnam, Muan-gun 58554, Korea; (S.S.); (D.A.); (J.P.L.)
| | - Min-Ho Oak
- College of Pharmacy, Mokpo National University, Jeonnam, Muan-gun 58554, Korea; (S.S.); (D.A.); (J.P.L.)
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Namdeo AG, Boddu SHS, Amawi H, Ashby CR, Tukaramrao DB, Trivedi P, Babu RJ, Tiwari AK. Flavonoids as Multi-Target Compounds: A Special Emphasis on their Potential as Chemo-adjuvants in Cancer Therapy. Curr Pharm Des 2020; 26:1712-1728. [PMID: 32003663 DOI: 10.2174/1381612826666200128095248] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Accepted: 01/24/2020] [Indexed: 02/06/2023]
Abstract
Flavonoids are low molecular weight, polyphenolic phytochemicals, obtained from secondary metabolism of various plant compounds. They have a spectrum of pharmacological efficacies, including potential anticancer efficacy. Natural flavonoids are present in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine. Flavonoids can attenuate or inhibit the initiation, promotion and progression of cancer by modulating various enzymes and receptors in diverse pathways that involve cellular proliferation, differentiation, apoptosis, inflammation, angiogenesis and metastasis. Furthermore, in vitro, flavonoids have been shown to reverse multidrug resistance when used as chemo-adjuvants. Flavonoids (both natural and synthetic analogues) interact with several oncogenic targets through dependent and independent mechanisms to mediate their anticancer efficacy in different types of cancer cells.
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Affiliation(s)
- Ajay G Namdeo
- Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, India
| | - Sai H S Boddu
- College of Pharmacy and Health Sciences, Ajman University, Ajman, United Arab Emirates
| | - Haneen Amawi
- Department of Pharmacy practice, Faculty of Pharmacy, Yarmouk University, P.O. BOX 566, Irbid 21163, Jordan
| | - Charles R Ashby
- Department of Pharmaceutical Sciences, St. John's University, Queens, NY 11439, United States
| | - Diwakar B Tukaramrao
- Department of Pharmacology and Experimental Therapeutics, The University of Toledo, Toledo, OH 43606, United States
| | - Piyush Trivedi
- Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, India
| | - R Jayachandra Babu
- Department of Drug Discovery and Development, Auburn University, Auburn, AL 36849, United States
| | - Amit K Tiwari
- Department of Pharmacology and Experimental Therapeutics, The University of Toledo, Toledo, OH 43606, United States
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Exploring the multifocal role of phytochemicals as immunomodulators. Biomed Pharmacother 2020; 133:110959. [PMID: 33197758 DOI: 10.1016/j.biopha.2020.110959] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 10/12/2020] [Accepted: 10/27/2020] [Indexed: 02/07/2023] Open
Abstract
A well-functioning immune system of the host body plays pivotal role in the maintenance of ordinary physiological and immunological functions as well as internal environment. Balanced immunity enhances defense mechanism against infection, diseases and unwanted pathogens to avoid hypersensitivity reactions and immune related diseases. The ideal immune responses are the results of corrective interaction between the innate immune cells and acquired components of the immune system. Recently, the interest towards the immune system increased as significant target of toxicity due to exposure of chemicals, drugs and environmental pollutants. Numerous factors are involved in altering the immune responses of the host such as sex, age, stress, malnutrition, alcohol, genetic variability, life styles, environmental-pollutants and chemotherapy exposure. Immunomodulation is any modification of immune responses, often involved induction, amplification, attenuation or inhibition of immune responses. Several synthetic or traditional medicines are available in the market which promptly have many serious adverse effects and create pathogenic resistance. Phytochemicals are naturally occurring molecules, which significantly play an imperative role in modulating favorable immune responses. The present review emphasizes on the risk factors associated with alterations in immune responses, and immunomodulatory activity of phytochemicals specifically, glycosides, alkaloids, phenolic acids, flavonoids, saponins, tannins and sterols and sterolins.
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Khademi A, Mansuri P, Pahlevan D, Bozorgi M, Nasiri M, Hejazi S, Azizian Z, Shirbeigi L. Efficacy of Pumpkin Ointment in Treatment of Chronic Hand Eczema: A Randomized, Active-Controlled, Double Blind Clinical Trial. IRANIAN JOURNAL OF PUBLIC HEALTH 2020; 49:1339-1347. [PMID: 33083301 PMCID: PMC7548497 DOI: 10.18502/ijph.v49i7.3588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Background Hand Eczema (HE) is chronic skin disease with a high prevalence in population. It has negative impact on the quality of life. Due to the public interest in herbal remedies, we attempt to assess the efficacy of pumpkin ointment in treatment of chronic HE in this research. Methods This study was conducted in an outpatient clinic at Imam-Khomeini Hospital in Tehran (Iran) from May 2015 to Nov 2016. We performed a double-blind trial on 60 patients with chronic HE randomized to four groups included pumpkin, betamethasone, eucerin and almond ointment (n=15 for each group) for 28 days. Patients were ordered to apply ointments twice a day. Hand Eczema Severity Index (HECSI) and Dermatology Life Quality Index (DLQI) of the patients were evaluated by a dermatologist on the 1st, 14th and 28th d after the start of treatment. Results Patients' DLQI scores in pumpkin and betamethasone group was significant and pumpkin group showed a better response in quality of life (P=0.001). Betamethasone and pumpkin ointment were effective and showed significant improvement compared with almond and eucerin and reduce HECSI scores (P=0.002 and P=0.012 respectively). Betamethasone ointment outcome on HECSI scores in comparison with topical pumpkin was significant (P<0.001). No clinically adverse effects were observed. Conclusion Although pumpkin ointment showed a better response in patients' DLQI in HE but it was less effective than betamethasone in decreasing HECSI.
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Affiliation(s)
- Alemeh Khademi
- Department of Traditional Medicine, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Parvin Mansuri
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Daryoush Pahlevan
- Research Center for Social Determinants of Health, Semnan University of Medical Sciences, Semnan, Iran
| | - Mahbubeh Bozorgi
- Department of Traditional Pharmacy, School of Iranian Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Malihe Nasiri
- Department of Biostatistics, School of Paramedical, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Somayeh Hejazi
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Azizian
- Department of Dermatology, Iran University of Medical Sciences, Tehran, Iran
| | - Laila Shirbeigi
- Department of Traditional Medicine, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Masuelli L, Benvenuto M, Focaccetti C, Ciuffa S, Fazi S, Bei A, Miele MT, Piredda L, Manzari V, Modesti A, Bei R. Targeting the tumor immune microenvironment with "nutraceuticals": From bench to clinical trials. Pharmacol Ther 2020; 219:107700. [PMID: 33045254 DOI: 10.1016/j.pharmthera.2020.107700] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/30/2020] [Indexed: 02/06/2023]
Abstract
The occurrence of immune effector cells in the tissue microenvironment during neoplastic progression is critical in determining tumor growth outcomes. On the other hand, tumors may also avoid immune system-mediated elimination by recruiting immunosuppressive leukocytes and soluble factors, which coordinate a tumor microenvironment that counteracts the efficiency of the antitumor immune response. Checkpoint inhibitor therapy results have indicated a way forward via activation of the immune system against cancer. Widespread evidence has shown that different compounds in foods, when administered as purified substances, can act as immunomodulators in humans and animals. Although there is no universally accepted definition of nutraceuticals, the term identifies a wide category of natural compounds that may impact health and disease statuses and includes purified substances from natural sources, plant extracts, dietary supplements, vitamins, phytonutrients, and various products with combinations of functional ingredients. In this review, we summarize the current knowledge on the immunomodulatory effects of nutraceuticals with a special focus on the cancer microenvironment, highlighting the conceptual benefits or drawbacks and subtle cell-specific effects of nutraceuticals for envisioning future therapies employing nutraceuticals as chemoadjuvants.
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Affiliation(s)
- Laura Masuelli
- Department of Experimental Medicine, University of Rome "Sapienza", Viale Regina Elena 324, 00161 Rome, Italy
| | - Monica Benvenuto
- Saint Camillus International University of Health and Medical Sciences, via di Sant'Alessandro 8, 00131 Rome, Italy; Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Chiara Focaccetti
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy; Department of Human Science and Promotion of the Quality of Life, San Raffaele University Rome, Via di Val Cannuta 247, 00166 Rome, Italy
| | - Sara Ciuffa
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Sara Fazi
- Department of Experimental Medicine, University of Rome "Sapienza", Viale Regina Elena 324, 00161 Rome, Italy
| | - Arianna Bei
- Medical School, University of Rome "Tor Vergata", 00133 Rome, Italy
| | - Martino Tony Miele
- Department of Experimental Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Lucia Piredda
- Department of Biology, University of Rome "Tor Vergata", Via della Ricerca Scientifica 1, 00133 Rome, Italy
| | - Vittorio Manzari
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Andrea Modesti
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Roberto Bei
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy; CIMER, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
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Benvenuto M, Albonici L, Focaccetti C, Ciuffa S, Fazi S, Cifaldi L, Miele MT, De Maio F, Tresoldi I, Manzari V, Modesti A, Masuelli L, Bei R. Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies. Int J Mol Sci 2020; 21:E6635. [PMID: 32927836 PMCID: PMC7555128 DOI: 10.3390/ijms21186635] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 09/07/2020] [Accepted: 09/08/2020] [Indexed: 02/06/2023] Open
Abstract
One of the hallmarks of cellular transformation is the altered mechanism of cell death. There are three main types of cell death, characterized by different morphological and biochemical features, namely apoptosis (type I), autophagic cell death (type II) and necrosis (type III). Autophagy, or self-eating, is a tightly regulated process involved in stress responses, and it is a lysosomal degradation process. The role of autophagy in cancer is controversial and has been associated with both the induction and the inhibition of tumor growth. Autophagy can exert tumor suppression through the degradation of oncogenic proteins, suppression of inflammation, chronic tissue damage and ultimately by preventing mutations and genetic instability. On the other hand, tumor cells activate autophagy for survival in cellular stress conditions. Thus, autophagy modulation could represent a promising therapeutic strategy for cancer. Several studies have shown that polyphenols, natural compounds found in foods and beverages of plant origin, can efficiently modulate autophagy in several types of cancer. In this review, we summarize the current knowledge on the effects of polyphenols on autophagy, highlighting the conceptual benefits or drawbacks and subtle cell-specific effects of polyphenols for envisioning future therapies employing polyphenols as chemoadjuvants.
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Affiliation(s)
- Monica Benvenuto
- Saint Camillus International University of Health and Medical Sciences, Via di Sant’Alessandro 8, 00131 Rome, Italy;
- Department of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, Via Montpellier 1, 00133 Rome, Italy; (L.A.); (C.F.); (S.C.); (L.C.); (F.D.M.); (I.T.); (V.M.); (A.M.)
| | - Loredana Albonici
- Department of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, Via Montpellier 1, 00133 Rome, Italy; (L.A.); (C.F.); (S.C.); (L.C.); (F.D.M.); (I.T.); (V.M.); (A.M.)
| | - Chiara Focaccetti
- Department of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, Via Montpellier 1, 00133 Rome, Italy; (L.A.); (C.F.); (S.C.); (L.C.); (F.D.M.); (I.T.); (V.M.); (A.M.)
- Department of Human Science and Promotion of the Quality of Life, San Raffaele University Rome, Via di Val Cannuta 247, 00166 Rome, Italy
| | - Sara Ciuffa
- Department of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, Via Montpellier 1, 00133 Rome, Italy; (L.A.); (C.F.); (S.C.); (L.C.); (F.D.M.); (I.T.); (V.M.); (A.M.)
| | - Sara Fazi
- Department of Experimental Medicine, University of Rome “Sapienza”, Viale Regina Elena 324, 00161 Rome, Italy; (S.F.); (L.M.)
| | - Loredana Cifaldi
- Department of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, Via Montpellier 1, 00133 Rome, Italy; (L.A.); (C.F.); (S.C.); (L.C.); (F.D.M.); (I.T.); (V.M.); (A.M.)
- Academic Department of Pediatrics (DPUO), Ospedale Pediatrico Bambino Gesù, IRCCS, Piazza Sant’Onofrio 4, 00165 Rome, Italy
| | - Martino Tony Miele
- Department of Experimental Medicine, University of Rome “Tor Vergata”, Via Montpellier 1, 00133 Rome, Italy;
| | - Fernando De Maio
- Department of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, Via Montpellier 1, 00133 Rome, Italy; (L.A.); (C.F.); (S.C.); (L.C.); (F.D.M.); (I.T.); (V.M.); (A.M.)
| | - Ilaria Tresoldi
- Department of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, Via Montpellier 1, 00133 Rome, Italy; (L.A.); (C.F.); (S.C.); (L.C.); (F.D.M.); (I.T.); (V.M.); (A.M.)
| | - Vittorio Manzari
- Department of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, Via Montpellier 1, 00133 Rome, Italy; (L.A.); (C.F.); (S.C.); (L.C.); (F.D.M.); (I.T.); (V.M.); (A.M.)
| | - Andrea Modesti
- Department of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, Via Montpellier 1, 00133 Rome, Italy; (L.A.); (C.F.); (S.C.); (L.C.); (F.D.M.); (I.T.); (V.M.); (A.M.)
| | - Laura Masuelli
- Department of Experimental Medicine, University of Rome “Sapienza”, Viale Regina Elena 324, 00161 Rome, Italy; (S.F.); (L.M.)
| | - Roberto Bei
- Department of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, Via Montpellier 1, 00133 Rome, Italy; (L.A.); (C.F.); (S.C.); (L.C.); (F.D.M.); (I.T.); (V.M.); (A.M.)
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Protective Effects of Polyphenols against Ischemia/Reperfusion Injury. Molecules 2020; 25:molecules25153469. [PMID: 32751587 PMCID: PMC7435883 DOI: 10.3390/molecules25153469] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Revised: 07/22/2020] [Accepted: 07/28/2020] [Indexed: 12/20/2022] Open
Abstract
Myocardial infarction (MI) is a leading cause of morbidity and mortality across the world. It manifests as an imbalance between blood demand and blood delivery in the myocardium, which leads to cardiac ischemia and myocardial necrosis. While it is not easy to identify the first pathogenic cause of MI, the consequences are characterized by ischemia, chronic inflammation, and tissue degeneration. A poor MI prognosis is associated with extensive cardiac remodeling. A loss of viable cardiomyocytes is replaced with fibrosis, which reduces heart contractility and heart function. Recent advances have given rise to the concept of natural polyphenols. These bioactive compounds have been studied for their pharmacological properties and have proven successful in the treatment of cardiovascular diseases. Studies have focused on their various bioactivities, such as their antioxidant and anti-inflammatory effects and free radical scavenging. In this review, we summarized the effects and benefits of polyphenols on the cardiovascular injury, particularly on the treatment of myocardial infarction in animal and human studies.
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Fanton S, Cardozo LFMF, Combet E, Shiels PG, Stenvinkel P, Vieira IO, Narciso HR, Schmitz J, Mafra D. The sweet side of dark chocolate for chronic kidney disease patients. Clin Nutr 2020; 40:15-26. [PMID: 32718711 DOI: 10.1016/j.clnu.2020.06.039] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 06/27/2020] [Accepted: 06/29/2020] [Indexed: 12/11/2022]
Abstract
Chocolate is a widely appreciated foodstuff with historical appreciation as a food from the gods. In addition to its highly palatable taste, it is a rich source of (poly)phenolics, which have several proposed salutogenic effects, including neuroprotective anti-inflammatory, anti-oxidant and cardioprotective capabilities. Despite the known benefits of this ancient foodstuff, there is a paucity of information on the effects of chocolate in the context of chronic kidney disease (CKD). This review focusses on the potential salutogenic contribution of chocolate intake, to mitigate inflammatory and oxidative burden in CKD, its potential, for cardiovascular protection and on the maintenance of diversity in gut microbiota, as well as clinical perspectives, on regular chocolate intake by CKD patients.
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Affiliation(s)
- Susane Fanton
- Renal Vida Association, Blumenau, SC, Brazil; Graduate Program in Cardiovascular Sciences, Federal Fluminense University, Niterói-Rio de Janeiro RJ, Brazil.
| | - Ludmila F M F Cardozo
- Graduate Program in Cardiovascular Sciences, Federal Fluminense University, Niterói-Rio de Janeiro RJ, Brazil
| | - Emilie Combet
- School of Medicine, College of Medical, Veterinary & Life Sciences, University of Glasgow, UK
| | - Paul G Shiels
- Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, University of Glasgow, UK
| | - Peter Stenvinkel
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Technology and Intervention, Karolinska Instituted, Stockholm, Sweden
| | | | | | | | - Denise Mafra
- Graduate Program in Cardiovascular Sciences, Federal Fluminense University, Niterói-Rio de Janeiro RJ, Brazil; Graduate Program in Medical Sciences, Federal Fluminense University, Niterói-Rio de Janeiro RJ, Brazil.
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