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Huang M, Xie X, Yuan R, Xin Q, Ma S, Guo H, Miao Y, Hu C, Zhu Y, Cong W. The multifaceted anti-atherosclerotic properties of herbal flavonoids: A comprehensive review. Pharmacol Res 2025; 211:107551. [PMID: 39701504 DOI: 10.1016/j.phrs.2024.107551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 12/12/2024] [Accepted: 12/12/2024] [Indexed: 12/21/2024]
Abstract
Atherosclerosis (AS) is a major etiological factor underpinning a spectrum of cardiovascular diseases, leading to cerebral infarction, coronary artery disease, and peripheral vascular disease. The chronic progression of AS, spanning from initial plaque formation to the occurrence of acute cardiovascular events, underscores the complexity of AS and the challenges it presents in terms of treatment. Currently, the clinical management of AS relies predominantly on statins and proprotein convertase subtilisin/kexin type 9 inhibitors, which primarily aim to reduce low-density lipoprotein levels and have demonstrated some therapeutic efficacy. Nevertheless, due to their potential side effects, there is a pressing need to actively investigate alternative treatment approaches. Researches on natural compounds derived from herbal medicines, such as flavonoids, hold significant promise in combating AS by regulating lipid metabolism, reducing oxidative stress and inflammation, inhibiting the proliferation of vascular smooth muscle cells, modulating autophagy and additional pathways. Various targets participate in these physiological processes, encompassing acyl-CoA: cholesterol acyltransferase (ACAT), ATP citrate lyase (ACLY), nuclear factor erythroid 2-related factor 2 (Nrf2), krüppel-like factor 2 (KLF2), NOD-like receptor protein 3 (NLRP3), transcription factor EB (TFEB) and so on. This comprehensive review endeavors to synthesize and analyse the most recent findings on herbal flavonoids, shedding light on their anti-atherosclerotic potential and the underlying protective mechanisms and related-targets, which might pave the way for the development of novel drug candidates or the optimization of flavonoid-based therapies.
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Affiliation(s)
- Meiwen Huang
- School of Pharmacy, Macau University of Science and Technology, Macau 999078, China; Laboratory of Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Xuena Xie
- School of Pharmacy, Macau University of Science and Technology, Macau 999078, China; Laboratory of Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Rong Yuan
- Laboratory of Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Qiqi Xin
- Laboratory of Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Shudong Ma
- Laboratory of Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China; Faculty of Chinese Medicine, Macau University of Science and Technology, Macau 999078, China
| | - Hongai Guo
- Laboratory of Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China; School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Yu Miao
- Laboratory of Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Chunyu Hu
- Department of Teaching Quality Construction, Graduate School, China Academy of Chinese Medical Sciences, 100700, China
| | - Yizhun Zhu
- School of Pharmacy, Macau University of Science and Technology, Macau 999078, China
| | - Weihong Cong
- School of Pharmacy, Macau University of Science and Technology, Macau 999078, China; Laboratory of Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
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Furukawa N, Kobayashi M, Ito M, Matsui H, Ohashi K, Murohara T, Takeda JI, Ueyama J, Hirayama M, Ohno K. Soy protein β-conglycinin ameliorates pressure overload-induced heart failure by increasing short-chain fatty acid (SCFA)-producing gut microbiota and intestinal SCFAs. Clin Nutr 2024; 43:124-137. [PMID: 39447394 DOI: 10.1016/j.clnu.2024.09.045] [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: 05/16/2024] [Revised: 09/26/2024] [Accepted: 09/27/2024] [Indexed: 10/26/2024]
Abstract
BACKGROUND AND AIMS Soybeans and their ingredients have antioxidant and anti-inflammatory effects on cardiovascular diseases. β-Conglycinin (β-CG), a major constituent of soy proteins, is protective against obesity, hypertension, and chronic kidney disease, but its effects on heart failure remain to be elucidated. We tested the effects of β-CG on left ventricular (LV) remodeling in pressure overload-induced heart failure. METHODS A transverse aortic constriction (TAC)-induced pressure overload was applied to the heart in 7-week-old C57BL6 male mice that were treated with β-CG, GlcNAc, or sodium propionate. Gut microbiota was analyzed by 16S rRNA sequencing. Fecal short-chain fatty acids (SCFAs) were quantified by GC-MS. The effects of oral antibiotics were examined in β-CG-fed mice. RESULTS β-CG ameliorated impaired cardiac contractions, cardiac hypertrophy, and myocardial fibrosis in TAC-operated mice. As β-CG is a highly glycosylated protein, we examined the effects of GlcNAc. GlcNAc had similar but less efficient effects on LV remodeling compared to β-CG. β-CG increased three major SCFA-producing intestinal bacteria, as well as fecal concentrations of SCFAs, in sham- and TAC-operated mice. Oral administration of antibiotics nullified the effects of β-CG in TAC-operated mice by markedly reducing SCFA-producing intestinal bacteria and fecal SCFAs. In contrast, oral administration of sodium propionate, one of SCFAs, ameliorated LV remodeling in TAC-operated mice to a similar extent as β-CG. CONCLUSIONS β-CG was protective against TAC-induced LV remodeling, which was likely to be mediated by increased SCFA-producing gut microbiota and increased intestinal SCFAs. Modified β-CG and/or derivatives arising from β-CG are expected to be developed as prophylactic and/or therapeutic agents to ameliorate devastating symptoms in heart failure.
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Affiliation(s)
- Nozomi Furukawa
- Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan; Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan.
| | - Miku Kobayashi
- Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan; Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Mikako Ito
- Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hiroki Matsui
- Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Maebashi, Japan
| | - Koji Ohashi
- Department of Molecular Medicine and Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Toyoaki Murohara
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Jun-Ichi Takeda
- Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan; Center for One Medicine Innovative Translational Research (COMIT), Institute for Advanced Study, Gifu University, Gifu, Japan
| | - Jun Ueyama
- Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masaaki Hirayama
- Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Occupational Therapy, Chubu University College of Life and Health Sciences, Kasugai, Japan
| | - Kinji Ohno
- Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan; Graduate School of Nutritional Sciences, Nagoya University of Arts and Sciences, Nisshin, Japan
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Vashi R, Joshi M, Patel BM. The therapeutic effect of NRF2 activator, ezetimibe, in cardiac cachexia. Fundam Clin Pharmacol 2024; 38:1131-1142. [PMID: 39008964 DOI: 10.1111/fcp.13029] [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: 06/15/2023] [Revised: 03/01/2024] [Accepted: 07/01/2024] [Indexed: 07/17/2024]
Abstract
INTRODUCTION Heart failure (HF) is caused by functional and structural irregularity leading to impaired ejection or filling capacity of the heart. HF leads to chronic inflammatory conditions in the heart leads to weight loss, anorexia, and muscle atrophy known as cachexia. The present study was carried out to investigate the role of Ezetimibe, an NRF2 activator, in cardiac cachexia and to develop a treatment strategy for cardiac cachexia. METHOD Balb/c mice of either sex at 6-8 weeks of age were given 2 mg/kg of doxorubicin in 0.9% sodium chloride solution intraperitoneally (i.p.) for the alternate days for the first week and then once a week for the next 4 weeks. After induction of cardiac atrophy, treatment with Ezetimibe (1.5 mg/kg, p.o) was given for the next 4 weeks. RESULT In the cardiac cachectic animals, a significant decrease in body weight, food, and water intake was observed. Cardiac cachectic animals showed a significant increase in serum glucose, total cholesterol, LDL, triglyceride, VLDL, CK-MB, LDH, and CRP levels. Cardiac atrophic index, heart weight to body weight ratios (HW/BW), right ventricular weight to heart weight ratios (RV/HW), and left ventricular weight to heart weight ratios (LV/HW), were significantly decreased in cardiac cachectic animals. The weights of the skeletal muscles such as EDL, gastrocnemius, soleus, tibialis anterior, and quadriceps muscles, and the weight of adipose tissue such as subcutaneous, visceral, perirenal, and brown adipose tissue were significantly decreased in the cardiac cachectic group relative to the normal group. Treatment with ezetimibe improves body weight, food intake, and water intake. Ezetimibe decreases serum glucose, total cholesterol, LDL, triglyceride, VLDL, CK-MB, LDH and CRP levels. Cardiac atrophic markers such as HW/BW, RV/HW, and LV/HW were improved. The weight of skeletal muscles and adipose tissue was increased after treatment with ezetimibe. CONCLUSION Our data showed that the NRF2 activator, Ezetimibe produces a beneficial effect on cardiac cachexia in the doxorubicin-induced cardiac cachexia model. Ezetimibe was successful to reduce the levels of inflammatory cytokines, ameliorate the effects on cardiac muscle wasting, lipid levels, fat tissues, and skeletal muscles.
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Affiliation(s)
- Ruju Vashi
- Institute of Pharmacy, Nirma University, Ahmedabad, India
| | - Mit Joshi
- Institute of Pharmacy, Nirma University, Ahmedabad, India
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Kuljarusnont S, Iwakami S, Iwashina T, Tungmunnithum D. Flavonoids and Other Phenolic Compounds for Physiological Roles, Plant Species Delimitation, and Medical Benefits: A Promising View. Molecules 2024; 29:5351. [PMID: 39598740 PMCID: PMC11596516 DOI: 10.3390/molecules29225351] [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: 10/08/2024] [Revised: 11/02/2024] [Accepted: 11/12/2024] [Indexed: 11/29/2024] Open
Abstract
Flavonoids and other phenolic constituents are a large group of plant metabolites that have long attracted interest from researchers worldwide due to their functions in plant physiology, as well as their huge number of benefits for human health and well-being. This review attempts to reveal a promising view of the major physiological roles of flavonoids and other phenolic phytochemical molecules, e.g., protection agents against UV damage, pathogen defense agents, detoxifying agents, and agents promoting pollen fertility and successful pollination. Besides, the value of both flavonoids and other phenolic phytochemicals for plant species delimitation was also emphasized for the first time with the determination of their major physiological roles. Furthermore, their medical benefits for mankind were also highlighted in this current work.
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Affiliation(s)
- Sompop Kuljarusnont
- Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand;
| | - Satoshi Iwakami
- Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu 183-8509, Tokyo, Japan;
| | - Tsukasa Iwashina
- Department of Botany, National Museum of Nature and Science (TNS), Tsukuba 305-0005, Ibaraki, Japan;
| | - Duangjai Tungmunnithum
- Department of Pharmaceutical Botany, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand
- Le Studium Institute for Advanced Studies, 45000 Orléans, France
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Ahmad F, Ranga PK, Fatma S, Vijaya Anand R. Domino Approach to Heterocycles-Based Unsymmetrical Triarylmethanes through Heteroannulation of 2-(2-Enynyl)-pyridines with Enaminones. J Org Chem 2024; 89:12104-12117. [PMID: 39137191 DOI: 10.1021/acs.joc.4c01006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/15/2024]
Abstract
Herein, we report a copper-catalyzed protocol to access unsymmetrical triarylmethanes containing both indolizine and the chromone scaffolds in the same molecule via a 5-endo-dig cyclization of 2-(2-enynyl)-pyridines followed by reaction with 2-hydroxyaryl enaminones. A variety of 2-hydroxyaryl enaminones and 2-(2-enynyl)-pyridines were subjected to reaction under the optimal reaction conditions, and the respective triarylmethanes were obtained in good to excellent yields.
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Affiliation(s)
- Feroz Ahmad
- Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER), Mohali, Sector 81, S.A.S. Nagar, Manauli (PO), Mohali 140306, Punjab, India
| | - Pavit K Ranga
- Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER), Mohali, Sector 81, S.A.S. Nagar, Manauli (PO), Mohali 140306, Punjab, India
| | - Shaheen Fatma
- Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER), Mohali, Sector 81, S.A.S. Nagar, Manauli (PO), Mohali 140306, Punjab, India
| | - Ramasamy Vijaya Anand
- Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER), Mohali, Sector 81, S.A.S. Nagar, Manauli (PO), Mohali 140306, Punjab, India
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Wu Q, Yao J, Xiao M, Zhang X, Zhang M, Xi X. Targeting Nrf2 signaling pathway: new therapeutic strategy for cardiovascular diseases. J Drug Target 2024; 32:874-883. [PMID: 38753446 DOI: 10.1080/1061186x.2024.2356736] [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: 04/02/2024] [Revised: 05/07/2024] [Accepted: 05/10/2024] [Indexed: 05/18/2024]
Abstract
Cardiovascular diseases (CVDs) are the leading cause of death globally, with oxidative stress (OS) identified as a primary contributor to their onset and progression. Given the elevated incidence and mortality rates associated with CVDs, there is an imperative need to investigate novel therapeutic strategies. Nuclear factor erythroid 2-related factor 2 (Nrf2), ubiquitously expressed in the cardiovascular system, has emerged as a promising therapeutic target for CVDs due to its role in regulating OS and inflammation. This review aims to delve into the mechanisms and actions of the Nrf2 pathway, highlighting its potential in mitigating the pathogenesis of CVDs.
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Affiliation(s)
- Qi Wu
- School of Medical Imaging, Bengbu Medical University, Bengbu, China
| | - Jiangting Yao
- School of Medical Imaging, Bengbu Medical University, Bengbu, China
| | - Mengyun Xiao
- School of Medical Imaging, Bengbu Medical University, Bengbu, China
| | - Xiawei Zhang
- School of Medical Imaging, Bengbu Medical University, Bengbu, China
| | - Mengxiao Zhang
- School of Pharmacy, Bengbu Medical University, Bengbu, China
| | - Xinting Xi
- School of Medical Imaging, Bengbu Medical University, Bengbu, China
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Yan M, Zhao Y, Feng S, Zheng J, Diao M, Zhang T. Hydroxyl group-induced enhancement of antioxidant activity of resveratrol over pterostilbene by binding to lactoferrin. Food Chem 2024; 441:138356. [PMID: 38183721 DOI: 10.1016/j.foodchem.2024.138356] [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: 09/27/2023] [Revised: 12/17/2023] [Accepted: 01/01/2024] [Indexed: 01/08/2024]
Abstract
The reduced antioxidant capacity of trans-resveratrol (Res) than the second generation of Res, namely pterostilbene (Pte), severely prohibits its in-depth intriguing radical-scavenging applications in food formulations. Herein, a unique chemical structure-dependent strategy was proposed to specifically enhance the radical scavenging activity of Res over Pte, relying on the two more hydroxyl groups on the A-benzene ring of Res, thus facilitating its binding with lactoferrin (LF) to form stable complexes through more hydrogen bonds. We prepared LF-Res and LF-Pte complexes, revealed their binding mechanisms by multispectral analysis and molecular docking/dynamics simulations, further evaluated their antioxidant properties via ABTS and DPPH assays and a model of inhibiting apple browning, eventually elucidated their structure-binding-property relationships. This contribution offers a new approach to restore the antioxidant capability of Res, also paves the way to precisely regulate the fascinating bioactivities of hydrophobic compounds by protein-binding in a chemical structure-, especially hydroxyl group-dependent manner.
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Affiliation(s)
- Mi Yan
- College of Food Science and Engineering, Jilin University, Changchun 130062, China
| | - Yueying Zhao
- College of Food Science and Engineering, Jilin University, Changchun 130062, China
| | - Sitong Feng
- College of Food Science and Engineering, Jilin University, Changchun 130062, China
| | - Jian Zheng
- College of Food Science and Engineering, Jilin University, Changchun 130062, China
| | - Mengxue Diao
- College of Food Science and Engineering, Jilin University, Changchun 130062, China
| | - Tiehua Zhang
- College of Food Science and Engineering, Jilin University, Changchun 130062, China.
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Song Z, Zhao F, Chu L, Lin H, Xiao Y, Fang Z, Wang X, Dong J, Lyu X, Yu D, Liu B, Gai J, Xu D. The GmSTF1/2-GmBBX4 negative feedback loop acts downstream of blue-light photoreceptors to regulate isoflavonoid biosynthesis in soybean. PLANT COMMUNICATIONS 2024; 5:100730. [PMID: 37817409 PMCID: PMC10873893 DOI: 10.1016/j.xplc.2023.100730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 07/18/2023] [Accepted: 10/05/2023] [Indexed: 10/12/2023]
Abstract
Isoflavonoids, secondary metabolites derived from the phenylalanine pathway, are predominantly biosynthesized in legumes, especially soybean (Glycine max). They are not only essential for plant responses to biotic and abiotic stresses but also beneficial to human health. In this study, we report that light signaling controls isoflavonoid biosynthesis in soybean. Blue-light photoreceptors (GmCRY1s, GmCRY2s, GmPHOT1s, and GmPHOT2s) and the transcription factors GmSTF1 and GmSTF2 promote isoflavonoid accumulation, whereas the E3 ubiquitin ligase GmCOP1b negatively regulates isoflavonoid biosynthesis. GmPHOT1s and GmPHOT2s stabilize GmSTF1/2, whereas GmCOP1b promotes the degradation of these two proteins in soybean. GmSTF1/2 regulate the expression of approximately 27.9% of the genes involved in soybean isoflavonoid biosynthesis, including GmPAL2.1, GmPAL2.3, and GmUGT2. They also repress the expression of GmBBX4, a negative regulator of isoflavonoid biosynthesis in soybean. In addition, GmBBX4 physically interacts with GmSTF1 and GmSTF2 to inhibit their transcriptional activation activity toward target genes related to isoflavonoid biosynthesis. Thus, GmSTF1/2 and GmBBX4 form a negative feedback loop that acts downstream of photoreceptors in the regulation of isoflavonoid biosynthesis. Our study provides novel insights into the control of isoflavonoid biosynthesis by light signaling in soybean and will contribute to the breeding of soybean cultivars with high isoflavonoid content through genetic and metabolic engineering.
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Affiliation(s)
- Zhaoqing Song
- National Center for Soybean Improvement, State Key Laboratory of Crop Genetics & Germplasm Enhancement and Utilization, College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China
| | - Fengyue Zhao
- National Center for Soybean Improvement, State Key Laboratory of Crop Genetics & Germplasm Enhancement and Utilization, College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China
| | - Li Chu
- National Center for Soybean Improvement, State Key Laboratory of Crop Genetics & Germplasm Enhancement and Utilization, College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China
| | - Huan Lin
- National Center for Soybean Improvement, State Key Laboratory of Crop Genetics & Germplasm Enhancement and Utilization, College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China
| | - Yuntao Xiao
- National Center for Soybean Improvement, State Key Laboratory of Crop Genetics & Germplasm Enhancement and Utilization, College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China
| | - Zheng Fang
- National Center for Soybean Improvement, State Key Laboratory of Crop Genetics & Germplasm Enhancement and Utilization, College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China
| | - Xuncheng Wang
- Beijing Key Laboratory of Environmentally Friendly Management of Fruit Diseases and Pests in North China, Institute of Plant and Environment Protection, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China
| | - Jie Dong
- Institute of Crop Science, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China
| | - Xiangguang Lyu
- State Key Laboratory of Crop Gene Resources and Breeding, Institute of Crop Science, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Deyue Yu
- National Center for Soybean Improvement, State Key Laboratory of Crop Genetics & Germplasm Enhancement and Utilization, College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China
| | - Bin Liu
- State Key Laboratory of Crop Gene Resources and Breeding, Institute of Crop Science, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
| | - Junyi Gai
- National Center for Soybean Improvement, State Key Laboratory of Crop Genetics & Germplasm Enhancement and Utilization, College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China.
| | - Dongqing Xu
- National Center for Soybean Improvement, State Key Laboratory of Crop Genetics & Germplasm Enhancement and Utilization, College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China.
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Yang Q, Wang G. Isoflavonoid metabolism in leguminous plants: an update and perspectives. FRONTIERS IN PLANT SCIENCE 2024; 15:1368870. [PMID: 38405585 PMCID: PMC10884283 DOI: 10.3389/fpls.2024.1368870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 01/29/2024] [Indexed: 02/27/2024]
Abstract
Isoflavonoids constitute a well-investigated category of phenylpropanoid-derived specialized metabolites primarily found in leguminous plants. They play a crucial role in legume development and interactions with the environment. Isoflavonoids usually function as phytoalexins, acting against pathogenic microbes in nature. Additionally, they serve as signaling molecules in rhizobial symbiosis. Notably, owing to their molecular structure resembling human estrogen, they are recognized as phytoestrogens, imparting positive effects on human health. This review comprehensively outlines recent advancements in research pertaining to isoflavonoid biosynthesis, transcriptional regulation, transport, and physiological functions, with a particular emphasis on soybean plants. Additionally, we pose several questions to encourage exploration into novel contributors to isoflavonoid metabolism and their potential roles in plant-microbe interactions.
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Affiliation(s)
- Qilin Yang
- Key Laboratory of Seed Innovation, Institute of Genetics and Developmental Biology, The Innovative Academy of Seed Design, Chinese Academy of Sciences, Beijing, China
- College of Advanced Agricultural Sciences, Chinese Academy of Sciences, Beijing, China
| | - Guodong Wang
- Key Laboratory of Seed Innovation, Institute of Genetics and Developmental Biology, The Innovative Academy of Seed Design, Chinese Academy of Sciences, Beijing, China
- College of Advanced Agricultural Sciences, Chinese Academy of Sciences, Beijing, China
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Pisoschi AM, Iordache F, Stanca L, Cimpeanu C, Furnaris F, Geicu OI, Bilteanu L, Serban AI. Comprehensive and critical view on the anti-inflammatory and immunomodulatory role of natural phenolic antioxidants. Eur J Med Chem 2024; 265:116075. [PMID: 38150963 DOI: 10.1016/j.ejmech.2023.116075] [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: 09/29/2023] [Revised: 12/17/2023] [Accepted: 12/18/2023] [Indexed: 12/29/2023]
Abstract
The immune response encompasses innate and adaptive immunity, each with distinct and specific activities. The innate immune system is constituted by phagocytic cells, macrophages, monocytes and neutrophils, the cascade system, and different classes of receptors such as toll-like receptors that are exploited by the innate immune cells. The adaptive immune system is antigen-specific, encompassing memory lymphocytes and the corresponding specific receptors. Inflammation is understood as an activation of different signaling pathways such as toll-like receptors or nuclear factor kappa-light-chain-enhancer of activated B cells, with an increase in nitric oxide, inflammatory cytokines and chemokines. Increased oxidative stress has been identified as main source of chronic inflammation. Phenolic antioxidants modulate the activities of lymphocytes and macrophages by impacting cytokines and nitric oxide release, exerting anti-inflammatory effect. The nuclear-factor kappa-light-chain-enhancer of activated B cells signaling pathway and the mitogen-activated protein kinase pathway are targeted, alongside an increase in nuclear factor erythroid 2-related factor mediated antioxidant response, triggering the activity of antioxidant enzymes. The inhibitive potential on phospholipase A2, cyclooxygenase and lipoxygenase in the arachidonic acid pathway, and the subsequent reduction in prostaglandin and leukotriene generation, reveals the potential of phenolics as inflammation antagonists. The immunomodulative potential encompasses the capacity to interfere with proinflammatory cytokine synthesis and with the expression of the corresponding genes. A diet rich in antioxidants can result in prevention of inflammation-related pathologies. More investigations are necessary to establish the role of these antioxidants in therapy. The appropriate delivery system and the prooxidant effects exhibited at large doses, or in the presence of heavy metal cations should be regarded.
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Affiliation(s)
- Aurelia Magdalena Pisoschi
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Veterinary Medicine, Department Preclinical Sciences, 105 Splaiul Independentei, 050097, Bucharest, Romania.
| | - Florin Iordache
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Veterinary Medicine, Department Preclinical Sciences, 105 Splaiul Independentei, 050097, Bucharest, Romania
| | - Loredana Stanca
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Veterinary Medicine, Department Preclinical Sciences, 105 Splaiul Independentei, 050097, Bucharest, Romania
| | - Carmen Cimpeanu
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Land Reclamation and Environmental Engineering, 59 Marasti Blvd, 011464, Bucharest, Romania
| | - Florin Furnaris
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Veterinary Medicine, Department Preclinical Sciences, 105 Splaiul Independentei, 050097, Bucharest, Romania
| | - Ovidiu Ionut Geicu
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Veterinary Medicine, Department Preclinical Sciences, 105 Splaiul Independentei, 050097, Bucharest, Romania; University of Bucharest, Faculty of Biology, Department Biochemistry and Molecular Biology, 91-95 Splaiul Independentei, 050095, Bucharest, Romania
| | - Liviu Bilteanu
- Molecular Nanotechnology Laboratory, National Institute for Research and Development in Microtechnologies, 126A, Erou Iancu Nicolae Street, 077190, Bucharest, Romania
| | - Andreea Iren Serban
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Veterinary Medicine, Department Preclinical Sciences, 105 Splaiul Independentei, 050097, Bucharest, Romania; University of Bucharest, Faculty of Biology, Department Biochemistry and Molecular Biology, 91-95 Splaiul Independentei, 050095, Bucharest, Romania
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Shirvanian K, Vali R, Farkhondeh T, Abderam A, Aschner M, Samarghandian S. Genistein Effects on Various Human Disorders Mediated via Nrf2 Signaling. Curr Mol Med 2024; 24:40-50. [PMID: 36443970 DOI: 10.2174/1566524023666221128162753] [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: 04/12/2022] [Revised: 08/03/2022] [Accepted: 09/14/2022] [Indexed: 11/30/2022]
Abstract
Genistein is a flavonoid, mostly found in soybean extract and is widely used for its antioxidant and anti-inflammatory activities. Genistein can interact with estrogen receptors due to its structural similarities to estrogen. It also inhibits protein tyrosine kinases and affects a variety of intracellular signal transductions. Genistein attenuates oxidative stress via diverse cellular mechanisms. However, nuclear factor (erythroidderived 2)-like 2 (Nrf2), the main antioxidant regulator, potentiates genistein's antioxidant effects and reduces cell damage. Nrf2 includes of seven domains and controls the expression of the phase II antioxidant enzymes to decrease oxidative stress. In this review, we address findings related to Nrf2 signaling pathways in the context of genistein's effects on diverse human diseases.
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Affiliation(s)
- Kasra Shirvanian
- School of Biology, College of science, University of Tehran, Tehran, Iran
| | - Reyhaneh Vali
- Department of Biology, Faculty of Modern Sciences, Tehran Medical Branch, Islamic Azad University, Tehran, Iran
| | - Tahereh Farkhondeh
- Department of Toxicology and Pharmacology, School of Pharmacy, Birjand University of Medical Sciences, Birjand, Iran
| | - Amir Abderam
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Forchheimer 209 1300 Morris Park Avenue, Bronx, New York, USA
| | - Saeed Samarghandian
- Healthy Ageing Research Centre, Neyshabur University of Medical Sciences, Neyshabur, Iran
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12
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Chang XQ, Xu L, Zuo YX, Liu YG, Li J, Chi HT. Emerging trends and hotspots of Nuclear factor erythroid 2-related factor 2 in nervous system diseases. World J Clin Cases 2023; 11:7833-7851. [DOI: 10.12998/wjcc.v11.i32.7833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 10/04/2023] [Accepted: 10/30/2023] [Indexed: 11/16/2023] Open
Abstract
BACKGROUND The Nuclear factor erythroid 2-related factor 2 (NRF2) transcription factor has attracted much attention in the context of neurological diseases. However, none of the studies have systematically clarified this field's research hotspots and evolution rules.
AIM To investigate the research hotspots, evolution patterns, and future research trends in this field in recent years.
METHODS We conducted a comprehensive literature search in the Web of Science Core Collection database using the following methods: (((((TS=(NFE2 L2)) OR TS=(Nfe2 L2 protein, mouse)) OR TS=(NF-E2-Related Factor 2)) OR TS=(NRF2)) OR TS=(NFE2L2)) OR TS=(Nuclear factor erythroid2-related factor 2) AND (((((((TS=(neurological diseases)) OR TS=(neurological disorder)) OR TS=(brain disorder)) OR TS=(brain injury)) OR TS=(central nervous system disease)) OR TS=(CNS disease)) OR TS=(central nervous system disorder)) OR TS=(CNS disorder) AND Language = English from 2010 to 2022. There are just two forms of literature available: Articles and reviews. Data were processed with the software Cite-Space (version 6.1. R6).
RESULTS We analyzed 1884 articles from 200 schools in 72 countries/regions. Since 2015, the number of publications in this field has increased rapidly. China has the largest number of publications, but the articles published in the United States have better centrality and H-index. Among the top ten authors with the most published papers, five of them are from China, and the author with the most published papers is Wang Handong. The institution with the most articles was Nanjing University. To their credit, three of the top 10 most cited articles were written by Chinese scholars. The keyword co-occurrence map showed that "oxidative stress", "NRF2", "activation", "expression" and "brain" were the five most frequently used keywords.
CONCLUSION Research on the role of NRF2 in neurological diseases continues unabated. Researchers in developed countries published more influential papers, while Chinese scholars provided the largest number of articles. There have been numerous studies on the mechanism of NRF2 transcription factor in neurological diseases. NRF2 is also emerging as a potentially effective target for the treatment of neurological diseases. However, despite decades of research, our knowledge of NRF2 transcription factor in nervous system diseases is still limited. Further studies are needed in the future.
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Affiliation(s)
- Xue-Qin Chang
- Department of Neurology, Xinhua Hospital Affiliated with Dalian University, Dalian 116011, Liaoning Province, China
| | - Ling Xu
- Department of Neurology, Xinhua Hospital Affiliated with Dalian University, Dalian 116011, Liaoning Province, China
| | - Yi-Xuan Zuo
- Department of Neurology, Xinhua Hospital Affiliated with Dalian University, Dalian 116011, Liaoning Province, China
| | - Yi-Guo Liu
- Department of Neurology, Xinhua Hospital Affiliated with Dalian University, Dalian 116011, Liaoning Province, China
| | - Jia Li
- Department of Neurology, Xinhua Hospital Affiliated with Dalian University, Dalian 116011, Liaoning Province, China
| | - Hai-Tao Chi
- Department of Neurology, Xinhua Hospital Affiliated with Dalian University, Dalian 116011, Liaoning Province, China
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13
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Gholami A, Darudi F, Baradaran HR, Hariri M. Effect of soy isoflavones on C-reactive protein in chronic inflammatory disorders. INT J VITAM NUTR RES 2023; 93:447-458. [PMID: 35291882 DOI: 10.1024/0300-9831/a000751] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
New evidence suggests that soy products might reduce chronic systemic inflammation. Therefore, we aimed to summarize the effect of soy isoflavones on serum concentration of C-reactive protein (CRP) among participants with chronic inflammatory disorders by conducting this study. Cochrane Library, Scopus, ISI Web of Science, clinicaltrials.gov, and PubMed were searched to identify randomized clinical trials (RCTs) published up to December 2020. The effect size was calculated by the mean change from baseline in concentrations of CRP and its standard deviation for both intervention and comparison groups. DerSimonian and Laird random-effects model was used when the heterogeneity test was statistically significant. In total, thirteen RCTs involving 1213 participants and ten RCTs involving 1052 participants were eligible for our systematic review and meta-analysis respectively. Study duration ranged from 4 to 96 weeks and soy isoflavones dose varied from 33 to 132 mg/day. Overall effect size indicated a non-significant effect on serum concentration of CRP following soy isoflavones intake (weighted mean differences (WMD)=-0.15 mg/L, 95% confidence interval (CI): -0.54, 0.23; p=0.430). Subgroup analysis revealed that soy isoflavones significantly reduced serum concentration of CRP in studies among participants with age >57 years and baseline CRP levels >3.75 mg/L. The present study proposed that soy isoflavones could not significantly reduce serum CRP levels. It seems more RCTs on participants with age more than 57 years and higher levels of CRP is necessary.
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Affiliation(s)
- Ali Gholami
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
- Department of Epidemiology and Biostatistics, School of Public Health, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Fatemeh Darudi
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Hamid Reza Baradaran
- Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
- Ageing Clinical and Experimental Research Team, Institute of Applied Health Sciences, School of Medicine, Medical Sciences and Nutrition University of Aberdeen, UK
| | - Mitra Hariri
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
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14
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Fan P, Meng H, Hao W, Zheng Y, Li H, Zhang Z, Du L, Guo X, Wang D, Wang Y, Wu H. Cardamonin targets KEAP1/NRF2 signaling for protection against atherosclerosis. Food Funct 2023; 14:4905-4920. [PMID: 37157847 DOI: 10.1039/d3fo00967j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/10/2023]
Abstract
Atherosclerosis (AS)-induced cardiovascular disease is a leading cause of death worldwide. To date, there is still a lack of effective approaches for AS intervention. Cardamonin (CAD) is a bioactive food component, but its effect on AS is unknown. In this work, CAD was investigated for its effect on AS using low-density lipoprotein receptor knockout mice and tumor necrosis factor-alpha (TNF-α)-stimulated endothelial cells (ECs). After a 12-week intervention, CAD was found to significantly prevent AS formation in the aortic root and aortic tree, reduce the necrotic core area, and inhibit aortic inflammation and oxidative stress. Moreover, CAD quenched TNF-α-provoked inflammation and oxidative stress in ECs. RNA-sequencing identified nuclear factor erythroid-2 related factor 2 (NFE2L2, NRF2)/heme oxidase 1 (HO1) signaling to be drastically activated by CAD. CAD is a known activator of the aryl hydrocarbon receptor (AHR) which is a transcription factor of the NFE2L2 gene. Surprisingly, AHR was not required for CAD's action on the activation of NRF2/HO1 signaling since AHR gene silencing did not reverse this effect. Furthermore, a molecular docking assay showed a strong binding potential of CAD to the Kelch domain of the Kelch-like ECH-associated protein 1 (KEAP1) which sequesters NRF2 in the cytoplasm. Both CAD and the Kelch domain inhibitor Ki696 promoted NRF2 nuclear translocation, whereas the combination of CAD and Ki696 did not yield a greater effect compared with either CAD or Ki696, confirming the interaction of CAD with the Kelch domain. This work provides an experimental basis for CAD as a novel and effective bioactive food component in future AS interventions.
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Affiliation(s)
- Pengfei Fan
- Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Rd., Jinan, Shandong 250012, China.
- Research Center of Translational Medicine, Jinan Central Hospital, Shandong University, 105 Jiefang Rd., Jinan, Shandong 250013, China
| | - Huali Meng
- Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Rd., Jinan, Shandong 250012, China.
- Research Center of Translational Medicine, Jinan Central Hospital, Shandong University, 105 Jiefang Rd., Jinan, Shandong 250013, China
| | - Wenhao Hao
- Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Rd., Jinan, Shandong 250012, China.
- Research Center of Translational Medicine, Jinan Central Hospital, Shandong University, 105 Jiefang Rd., Jinan, Shandong 250013, China
| | - Yan Zheng
- Research Center of Translational Medicine, Jinan Central Hospital, Shandong University, 105 Jiefang Rd., Jinan, Shandong 250013, China
| | - Hui Li
- NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Rd., Jinan, Shandong 250012, China
| | - Zhiyue Zhang
- NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Rd., Jinan, Shandong 250012, China
| | - Lei Du
- Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Rd., Jinan, Shandong 250012, China.
- Research Center of Translational Medicine, Jinan Central Hospital, Shandong University, 105 Jiefang Rd., Jinan, Shandong 250013, China
| | - Xin Guo
- Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Rd., Jinan, Shandong 250012, China.
- Research Center of Translational Medicine, Jinan Central Hospital, Shandong University, 105 Jiefang Rd., Jinan, Shandong 250013, China
| | - Dongliang Wang
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), 74 Zhongshan Road II, Guangzhou 510080, China
| | - Yunyan Wang
- Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 107 Wenhuaxi Rd., Jinan, Shandong 250012, China.
| | - Hao Wu
- Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Rd., Jinan, Shandong 250012, China.
- Research Center of Translational Medicine, Jinan Central Hospital, Shandong University, 105 Jiefang Rd., Jinan, Shandong 250013, China
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15
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Soy Extract, Rich in Hydroxylated Isoflavones, Exhibits Antidiabetic Properties In Vitro and in Drosophila melanogaster In Vivo. Nutrients 2023; 15:nu15061392. [PMID: 36986122 PMCID: PMC10054920 DOI: 10.3390/nu15061392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 03/03/2023] [Accepted: 03/07/2023] [Indexed: 03/15/2023] Open
Abstract
In the context of the growing prevalence of type 2 diabetes (T2DM), control of postprandial hyperglycemia is crucial for its prevention. Blood glucose levels are determined by various factors including carbohydrate hydrolyzing enzymes, the incretin system and glucose transporters. Furthermore, inflammatory markers are recognized predictors of diabetes outcome. Although there is some evidence that isoflavones may exhibit anti-diabetic properties, little is known about to what extent their corresponding hydroxylated metabolites may affect glucose metabolism. We evaluated the ability of a soy extract before (pre-) and after (post-) fermentation to counteract hyperglycemia in vitro and in Drosophila melanogaster in vivo. Fermentation with Aspergillus sp. JCM22299 led to an enrichment of hydroxy-isoflavones (HI), including 8-hydroxygenistein, 8-hydroxyglycitein and 8-hydroxydaidzein, accompanied by an enhanced free radical scavenging activity. This HI-rich extract demonstrated inhibitory activity towards α-glucosidase and a reduction of dipeptidyl peptidase-4 enzyme activity. Both the pre- and post-fermented extracts significantly inhibited the glucose transport via sodium-dependent glucose transporter 1. Furthermore, the soy extracts reduced c-reactive protein mRNA and secreted protein levels in interleukin-stimulated Hep B3 cells. Finally, supplementation of a high-starch D. melanogaster diet with post-fermented HI-rich extract decreased the triacylglyceride content of female fruit flies, confirming its anti-diabetic properties in an in vivo model.
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16
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Glutathione system enhancement for cardiac protection: pharmacological options against oxidative stress and ferroptosis. Cell Death Dis 2023; 14:131. [PMID: 36792890 PMCID: PMC9932120 DOI: 10.1038/s41419-023-05645-y] [Citation(s) in RCA: 58] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 01/31/2023] [Accepted: 02/02/2023] [Indexed: 02/17/2023]
Abstract
The glutathione (GSH) system is considered to be one of the most powerful endogenous antioxidant systems in the cardiovascular system due to its key contribution to detoxifying xenobiotics and scavenging overreactive oxygen species (ROS). Numerous investigations have suggested that disruption of the GSH system is a critical element in the pathogenesis of myocardial injury. Meanwhile, a newly proposed type of cell death, ferroptosis, has been demonstrated to be closely related to the GSH system, which affects the process and outcome of myocardial injury. Moreover, in facing various pathological challenges, the mammalian heart, which possesses high levels of mitochondria and weak antioxidant capacity, is susceptible to oxidant production and oxidative damage. Therefore, targeted enhancement of the GSH system along with prevention of ferroptosis in the myocardium is a promising therapeutic strategy. In this review, we first systematically describe the physiological functions and anabolism of the GSH system, as well as its effects on cardiac injury. Then, we discuss the relationship between the GSH system and ferroptosis in myocardial injury. Moreover, a comprehensive summary of the activation strategies of the GSH system is presented, where we mainly identify several promising herbal monomers, which may provide valuable guidelines for the exploration of new therapeutic approaches.
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17
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Xu X, Guo L, Liu Y, He X, Guo Y, Zeng Y. Silver‐Catalyzed Regioselective Alkylation of Chromones with Carboxylic Acids. ChemistrySelect 2022. [DOI: 10.1002/slct.202202650] [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]
Affiliation(s)
- Xiao‐Feng Xu
- School of Pharmaceutical Science Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research Hengyang Medical School University of South China Hengyang Hunan 421001 China
| | - Lu Guo
- Department of Sports Medicine Affiliated Nanhua Hospital Hengyang Medical School University of South China Hengyang Hunan 421001 China
| | - Yuan‐Xin Liu
- School of Pharmaceutical Science Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research Hengyang Medical School University of South China Hengyang Hunan 421001 China
| | - Xing‐Zi He
- School of Pharmaceutical Science Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research Hengyang Medical School University of South China Hengyang Hunan 421001 China
| | - Yu Guo
- School of Pharmaceutical Science Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research Hengyang Medical School University of South China Hengyang Hunan 421001 China
| | - Yao‐Fu Zeng
- School of Pharmaceutical Science Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research Hengyang Medical School University of South China Hengyang Hunan 421001 China
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18
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Jiao Y, Li X, Tang Y, Peng Y, Chen G, Wang X, Yan L, Liu H, Nie Z. Distribution and metabolism of daidzein and its benzene sulfonates in vivo (in mice) based on MALDI-TOF MSI. Front Pharmacol 2022; 13:918087. [PMID: 36034806 PMCID: PMC9399426 DOI: 10.3389/fphar.2022.918087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 07/05/2022] [Indexed: 11/13/2022] Open
Abstract
Daidzein (D1) has been proved to be of great benefit to human health. More and more attention was paid to the metabolic process of D1. Most studies focused on the metabolites of D1 and analogs were determined through the excretion of animals and humans by traditional HPLC-MS, while their in situ distribution and metabolism in organs in vivo has not been reported. In our group, novel daidzein sulfonate derivatives were synthesized and confirmed to have excellent pharmaceutical properties. They exhibited good anti-inflammatory, inhibitory activities on human vascular smooth muscle cell proliferation and other bioactivities. Compared with traditional analytical methods, matrix-assisted laser desorption ionization time-of-flight mass spectrometry imaging (MALDI-TOF MSI) can directly analyze the distribution of compounds in tissues and organs. In this study, we investigate the in situ distribution and metabolism of D1 and its derivatives (DD2, DD3) in the organs of mice based on MALDI-TOF MSI for the first time. Trace prototype compounds were detected in the plasma 4 h after the intravenous injection of D1, DD2, and DD3. Seven phase I metabolites and seven phase II metabolites were detected. D1 sulfates were found in the plasma and in organs except the heart. The presence of D1 and DD3 monosulfates in the brain indicated that they could penetrate the blood–brain barrier. DD2 and DD3 could be hydrolyzed into D1 and their metabolic pathways were similar to those of D1. In addition, a ligand-receptor docking of D1 and DD2 with mitogen-activated protein kinase 8 (JNK1) was performed because of their significant anti-inflammatory activities through the JNK signaling pathway. It showed that the binding energy of DD2 with JNK1 was obviously lower than that of D1 which was consistent with their anti-inflammatory activities. It provided a theoretical basis for further validation of their anti-inflammatory mechanism at the protein level. In summary, the research will provide beneficial guidance for further pharmacological, toxicological studies and the clinical-use research of these compounds.
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Affiliation(s)
- Yanxiao Jiao
- College of Chemistry and Chemical Engineering, Jiangxi Province Engineering Research Center of Ecological Chemical Industry, Jiujiang University, Jiujiang, China
| | - Xueqin Li
- College of Chemistry and Chemical Engineering, Jiangxi Province Engineering Research Center of Ecological Chemical Industry, Jiujiang University, Jiujiang, China
| | - Yao Tang
- State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science and Technology, Tianjin, China
| | - You Peng
- College of Chemistry and Chemical Engineering, Jiangxi Province Engineering Research Center of Ecological Chemical Industry, Jiujiang University, Jiujiang, China
- *Correspondence: You Peng, ; Zongxiu Nie,
| | - Guisen Chen
- College of Chemistry and Chemical Engineering, Jiangxi Province Engineering Research Center of Ecological Chemical Industry, Jiujiang University, Jiujiang, China
| | - Xin Wang
- College of Chemistry and Chemical Engineering, Jiangxi Province Engineering Research Center of Ecological Chemical Industry, Jiujiang University, Jiujiang, China
| | - Long Yan
- College of Chemistry and Chemical Engineering, Jiangxi Province Engineering Research Center of Ecological Chemical Industry, Jiujiang University, Jiujiang, China
| | - Huihui Liu
- Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry Chinese Academy of Sciences, Beijing, China
| | - Zongxiu Nie
- Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry Chinese Academy of Sciences, Beijing, China
- *Correspondence: You Peng, ; Zongxiu Nie,
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19
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Maximizing the Estrogenic Potential of Soy Isoflavones through the Gut Microbiome: Implication for Cardiometabolic Health in Postmenopausal Women. Nutrients 2022; 14:nu14030553. [PMID: 35276910 PMCID: PMC8840243 DOI: 10.3390/nu14030553] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 01/17/2022] [Accepted: 01/21/2022] [Indexed: 12/24/2022] Open
Abstract
Soy isoflavones have been suggested as an alternative treatment for managing postmenopausal symptoms and promoting long-term health due to their structural similarity to mammalian estrogen and ability to bind to estrogen receptors. Among all soy isoflavones and their metabolites, (S)-equol is known for having the strongest estrogenic activity. Equol is a metabolite of the soy isoflavone daidzein produced through intestinal bacterial metabolism. However, more than half of the human population is not able to produce equol due to the lack of equol-producing bacteria in their gastrointestinal tract. The interpersonal variations in the gut microbiome complicate the interpretation of data collected from humans. Furthermore, because rodents are efficient equol-producers, translatability between rodent models and humans is challenging. Herein, we first summarized the current knowledge of the microbial conversion of daidzein to equol, its relation to health, and proposed the need for developing model systems by which equol production can be manipulated while controlling other known confounding factors. Determining the necessity of equol-producing capacity within a gut microbial community when consuming soy as a functional ingredient, and identifying strategies to maximize equol production by modulating the gut microbiome, may provide future therapeutic approaches to improve the health of postmenopausal women.
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20
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Niu HZ, Liu CM, Hou WC, Li SN, Zhang YC, Liu Z, Yun HC. Development of a method to screen and isolate xanthine oxidase inhibitors from black bean in a single step: Hyphenation of semipreparative liquid chromatography and stepwise flow rate countercurrent chromatography. J Sep Sci 2021; 45:492-506. [PMID: 34799974 DOI: 10.1002/jssc.202100663] [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: 08/22/2021] [Revised: 11/02/2021] [Accepted: 11/07/2021] [Indexed: 11/06/2022]
Abstract
Black bean, in which isoflavones are the main active constituent, also contains saponins and monoterpenes. Soybean isoflavone is a secondary metabolite that is formed during the growth of soybean; it exhibits antioxidant and cardiovascular activities and traces estrogen-like effects. In this study, black bean isoflavones were extracted with n-butanol, and ultrafiltration-liquid chromatography-mass spectrometry was used to screen their activity. Subsequently, the inhibitors were isolated and purified using semipreparative liquid chromatography and stepwise flow rate countercurrent chromatography. Thereafter, five active compounds were identified using mass spectrometry and nuclear magnetic resonance experiments. Finally, the inhibition types of the xanthine oxidase inhibitors were determined using enzymatic kinetic studies. The IC50 values of daidzin, glycitein-7-O-glucoside, genistin, daidzein, and genistein were determined to be 35.08, 56.22, 30.76, 68.79, and 95.37 μg/mL, respectively. Daidzin, genistin, and daidzein exhibited reversible inhibition, whereas glycitein-7-O-glucoside and genistein presented irreversible inhibition. This novel approach, which was based on ultrafiltration-liquid chromatography-mass spectrometry and stepwise flow rate countercurrent chromatography, is a powerful method for screening and isolating xanthine oxidase inhibitors from complex matrices. The study of enzyme inhibition types is helpful for understanding the underlying inhibition mechanism. Therefore, a beneficial platform was developed for the large-scale production of bioactive and nutraceutical ingredients.
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Affiliation(s)
- Hua-Zhou Niu
- Central Laboratory, Changchun Normal University, Changchun, P. R. China
| | - Chun-Ming Liu
- Central Laboratory, Changchun Normal University, Changchun, P. R. China
| | - Wan-Chao Hou
- Central Laboratory, Changchun Normal University, Changchun, P. R. China
| | - Sai-Nan Li
- Central Laboratory, Changchun Normal University, Changchun, P. R. China
| | - Yu-Chi Zhang
- Central Laboratory, Changchun Normal University, Changchun, P. R. China
| | - Zhen Liu
- Central Laboratory, Changchun Normal University, Changchun, P. R. China
| | - Hao-Cheng Yun
- Central Laboratory, Changchun Normal University, Changchun, P. R. China
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21
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Lepidium meyenii (maca) and soy isoflavones reduce cardiac stunning of ischemia-reperfusion in rats by mitochondrial mechanisms. J Tradit Complement Med 2021; 11:471-480. [PMID: 34765511 PMCID: PMC8572714 DOI: 10.1016/j.jtcme.2021.03.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Revised: 03/22/2021] [Accepted: 03/30/2021] [Indexed: 11/21/2022] Open
Abstract
Background and aim Phytoestrogens are traditionally used for cardiovascular risks but direct effects on the ischemic heart remain unclear. Plants with phytoestrogens are used for reducing menopausic symptoms and they could also be cardioprotectives. Here we investigated whether maca (Lepidium meyenii) contains isoflavones and prevents cardiac stunning, in comparison to soy isoflavones. Experimental procedure Both products were orally and daily administered to rats during 1 week before exposing isolated hearts to ischemia/reperfusion (I/R). Young male (YM), female (YF) and aged female (AgF) rats treated with maca (MACA, 1 g/kg/day) or soy isoflavones (ISOF, 100 mg/kg/day) were compared to acute daidzein (DAZ, 5 mg/kg i.p.) and non-treated rat groups. Isolated ventricles were perfused inside a calorimeter to simultaneously measure contractile and calorimetrical signals before and during I/R. Results and conclusions Maca has genistein and daidzein. MACA and ISOF improved the post-ischemic contractile recovery (PICR) and muscle economy (P/Ht) in YM and YF hearts, but not in AgF hearts. DAZ improved PICR and P/Ht more in YM than in YF. The mKATP channels blockade reduced both PICR and P/Ht in DAZ-treated YM hearts, without affecting them in ISOF or MACA-treated YM hearts. In MACA treated YF hearts, the simultaneous blockade of NOS and mKATP channels, or the mNCX blockade reduced cardioprotection. Results show that subacute oral treatment with maca or with soy isoflavones was strongly preventive of cardiac ischemic dysfunction, more than the acute administration of a pure isoflavone (daidzein, genistein). Maca induced synergistic and complex mechanisms which prevented mitochondrial calcium overload.
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Key Words
- 5-HD, 5-hydroxydecanoate
- AgF, aged female rats
- CICUAL, Institutional Committee for Care of Laboratory Animals
- CONICET, National Council of Scientific and Technical Research
- Calcium
- Cardiomyocytes
- DAZ, daidzein
- DMSO, dimethylsulphoxide
- Daidzein
- F, Fisher coefficient for variance statistical test
- HPLC, high performance liquid chromatography
- Ht, total heat rate
- I/R, ischemia and reperfusion
- ISOF, soy isoflavones
- Isoflavones
- MACA, Lepidium meyenii root powder
- Maca
- Mitochondria
- Myocardial economy
- NOS
- NOS, nitric oxide synthases
- P, maximal pressure developed in contraction
- P/Ht, muscle economy
- PICR, post-ischemic contractile recovery
- PKC, protein-kinase C
- ROS, reactive oxygen species
- SEM, standard error of media
- TFT, triphenyltetrazolium chloride
- YF, young female rats
- YM, young male
- i.p, intraperitoneal
- l-NAME, Nω-nitro-l-arginine methyl ester hydrochloride
- mKATP channels
- mKATP, mitochondrial ATP-dependent K+ channels
- mNCX
- mNCX, mitochondrial Na/Ca exchanger
- ΔLVEDP, resting diastolic pressure
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Nazari-Khanamiri F, Ghasemnejad-Berenji M. Cellular and molecular mechanisms of genistein in prevention and treatment of diseases: An overview. J Food Biochem 2021; 45:e13972. [PMID: 34664285 DOI: 10.1111/jfbc.13972] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 09/22/2021] [Accepted: 10/01/2021] [Indexed: 01/01/2023]
Abstract
Genistein is the simplest secondary metabolite in soybeans and belongs to a group of compounds called isoflavones. It is a phytoestrogen and it makes up more than 60% of soy isoflavones. Studies have shown the anti-inflammatory, anti-apoptotic, and anti-angiogenic effects of genistein in addition to its modulatory effects on steroidal hormone receptors. In this review, we discuss the pharmacologic and therapeutic effects of genistein on various diseases. PRACTICAL APPLICATIONS: In this review, we have discussed the therapeutic effects of genistein as the main constituent of soybeans on health conditions. Its antioxidant, anti-inflammatory, anti-apoptotic and, anti-angiogenic effects need more attention. The pharmacological properties of genistein make this natural isoflavone a potential treatment for various diseases such as postmenopausal symptoms, cancer, bone, brain, and heart diseases. Special emphasis should be given to it, resulting in using it in clinical as a safe, potent, and bioactive molecule.
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Affiliation(s)
| | - Morteza Ghasemnejad-Berenji
- Experimental and Applied Pharmaceutical Research Center, Urmia University of Medical Sciences, Urmia, Iran
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran
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Abdelrahman M, Wei Z, Rohila JS, Zhao K. Multiplex Genome-Editing Technologies for Revolutionizing Plant Biology and Crop Improvement. FRONTIERS IN PLANT SCIENCE 2021; 12:721203. [PMID: 34691102 PMCID: PMC8526792 DOI: 10.3389/fpls.2021.721203] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Accepted: 09/01/2021] [Indexed: 05/26/2023]
Abstract
Multiplex genome-editing (MGE) technologies are recently developed versatile bioengineering tools for modifying two or more specific DNA loci in a genome with high precision. These genome-editing tools have greatly increased the feasibility of introducing desired changes at multiple nucleotide levels into a target genome. In particular, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) [CRISPR/Cas] system-based MGE tools allow the simultaneous generation of direct mutations precisely at multiple loci in a gene or multiple genes. MGE is enhancing the field of plant molecular biology and providing capabilities for revolutionizing modern crop-breeding methods as it was virtually impossible to edit genomes so precisely at the single base-pair level with prior genome-editing tools, such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs). Recently, researchers have not only started using MGE tools to advance genome-editing applications in certain plant science fields but also have attempted to decipher and answer basic questions related to plant biology. In this review, we discuss the current progress that has been made toward the development and utilization of MGE tools with an emphasis on the improvements in plant biology after the discovery of CRISPR/Cas9. Furthermore, the most recent advancements involving CRISPR/Cas applications for editing multiple loci or genes are described. Finally, insights into the strengths and importance of MGE technology in advancing crop-improvement programs are presented.
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Affiliation(s)
- Mohamed Abdelrahman
- National Key Facility for Crop Gene Resources and Genetic Improvement, Institute of Crop Science, Chinese Academy of Agricultural Sciences, Beijing, China
- Rice Research and Training Center, Field Crops Research Institute, Agricultural Research Center, Kafr El-Shaikh, Egypt
| | - Zheng Wei
- National Key Facility for Crop Gene Resources and Genetic Improvement, Institute of Crop Science, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Jai S. Rohila
- Dale Bumpers National Rice Research Center, United States Department of Agriculture - Agricultural Research Services, Stuttgart, AR, United States
| | - Kaijun Zhao
- National Key Facility for Crop Gene Resources and Genetic Improvement, Institute of Crop Science, Chinese Academy of Agricultural Sciences, Beijing, China
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24
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Zhou X, Du HH, Jiang M, Zhou C, Deng Y, Long X, Zhao X. Antioxidant Effect of Lactobacillus fermentum CQPC04-Fermented Soy Milk on D-Galactose-Induced Oxidative Aging Mice. Front Nutr 2021; 8:727467. [PMID: 34513906 PMCID: PMC8429822 DOI: 10.3389/fnut.2021.727467] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 08/09/2021] [Indexed: 01/11/2023] Open
Abstract
The aim of this study is to evaluate the changes in soy isoflavones and peptides in soy milk after lactic acid bacterial fermentation, and explore the positive effects of fermented soy milk on an oxidative aging mouse model induced with D-galactose. We found that free soybean isoflavones and peptides increased after soy milk was fermented by Lactobacillus fermentum CQPC04. The in vivo results indicated that L. fermentum CQPC04-fermented soy milk enhanced the organ index of the liver and spleen, and improved the pathological morphology of the liver, spleen, and skin. L. fermentum CQPC04-fermented soy milk increased the enzymatic activity of glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD), and catalase (CAT), increased glutathione (GSH), but decreased the levels of nitric oxide (NO) and malondialdehyde (MDA) in serum, liver, and brain tissues of oxidative aging mice. The above mentioned fermented soy milk also increased the levels of collagen I (Col I), hyaluronic acid (HA), and collagen III (Col III), and decreased the levels of advanced glycation End products (AGEs) and hydrogen peroxide (H2O2). The RT-qPCR results showed that L. fermentum CQPC04-fermented soy milk upregulated the mRNA expression of nuclear factor erythroid 2?related factor (Nrf2), heme oxygenase-1 (HMOX1), quinone oxido-reductase 1 (Nqo1), neuronal nitric oxide synthase (NOS1), endothelial nitric oxide synthase (NOS3), Cu/Zn–superoxide dismutase (Cu/Zn-SOD), Mn–superoxide dismutase (Mn-SOD), and CAT, but downregulated the expression of inducible nitric oxide synthase (NOS2) and glutamate cysteine ligase modifier subunit (Gclm) in liver and spleen tissues. Lastly, the fermented soy milk also increased the gene expression of Cu/Zn-SOD, Mn-SOD, CAT, GSH-Px, matrix metalloproteinases 1 (TIMP1), and matrix metalloproteinases 2 (TIMP2), and decreased the expression of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) in skin tissue. In conclusion, L. fermentum CQPC04-fermented soy milk was able to satisfactorily delay oxidative aging effects, and its mechanism may be related to the increase in free soy isoflavones and peptides.
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Affiliation(s)
- Xianrong Zhou
- Chongqing Collaborative Innovation Center for Functional Food, Chongqing Engineering Research Center of Functional Food, Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing, China.,Department of Food and Nutrition, College of Medical and Life Sciences, Silla University, Busan, South Korea
| | - Hang-Hang Du
- Department of Plastic Surgery, Chongqing Huamei Plastic Surgery Hospital, Chongqing, China
| | - Meiqing Jiang
- Chongqing Collaborative Innovation Center for Functional Food, Chongqing Engineering Research Center of Functional Food, Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing, China
| | - Chaolekang Zhou
- Chongqing Collaborative Innovation Center for Functional Food, Chongqing Engineering Research Center of Functional Food, Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing, China
| | - Yuhan Deng
- Chongqing Collaborative Innovation Center for Functional Food, Chongqing Engineering Research Center of Functional Food, Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing, China
| | - Xingyao Long
- Chongqing Collaborative Innovation Center for Functional Food, Chongqing Engineering Research Center of Functional Food, Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing, China
| | - Xin Zhao
- Chongqing Collaborative Innovation Center for Functional Food, Chongqing Engineering Research Center of Functional Food, Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing, China
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25
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Chun KS, Raut PK, Kim DH, Surh YJ. Role of chemopreventive phytochemicals in NRF2-mediated redox homeostasis in humans. Free Radic Biol Med 2021; 172:699-715. [PMID: 34214633 DOI: 10.1016/j.freeradbiomed.2021.06.031] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 06/14/2021] [Accepted: 06/24/2021] [Indexed: 12/17/2022]
Abstract
While functioning as a second messenger in the intracellular signaling, ROS can cause oxidative stress when produced in excess or not neutralized/eliminated properly. Excessive ROS production is implicated in multi-stage carcinogenesis. Our body is equipped with a defense system to cope with constant oxidative stress caused by the external insults, including redox-cycling chemicals, radiation, and microbial infection as well as endogenously generated ROS. The transcription factor, nuclear transcription factor erythroid 2-related factor 2 (NRF2) is a master switch in the cellular antioxidant signaling and plays a vital role in adaptive survival response to ROS-induced oxidative stress. Although NRF2 is transiently activated when cellular redox balance is challenged, this can be overwhelmed by massive oxidative stress. Therefore, it is necessary to maintain the NRF2-mediated antioxidant defense capacity at an optimal level. This review summarizes the natural NRF2 inducers/activators, especially those present in the plant-based diet, in relation to their cancer chemopreventive potential in humans. The molecular mechanisms underlying their stabilization or activation of NRF2 are also discussed.
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Affiliation(s)
- Kyung-Soo Chun
- College of Pharmacy, Keimyung University, Daegu 42691, South Korea
| | - Pawan Kumar Raut
- College of Pharmacy, Keimyung University, Daegu 42691, South Korea
| | - Do-Hee Kim
- Department of Chemistry, College of Convergence and Integrated Science, Kyonggi University, Suwon, Gyeonggi-do 16227, South Korea
| | - Young-Joon Surh
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, South Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, South Korea; Cancer Research Institute, Seoul National University, Seoul 03080, South Korea.
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26
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Sharifi-Rad J, Quispe C, Imran M, Rauf A, Nadeem M, Gondal TA, Ahmad B, Atif M, Mubarak MS, Sytar O, Zhilina OM, Garsiya ER, Smeriglio A, Trombetta D, Pons DG, Martorell M, Cardoso SM, Razis AFA, Sunusi U, Kamal RM, Rotariu LS, Butnariu M, Docea AO, Calina D. Genistein: An Integrative Overview of Its Mode of Action, Pharmacological Properties, and Health Benefits. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:3268136. [PMID: 34336089 PMCID: PMC8315847 DOI: 10.1155/2021/3268136] [Citation(s) in RCA: 124] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 06/11/2021] [Accepted: 06/28/2021] [Indexed: 12/15/2022]
Abstract
Genistein is an isoflavone first isolated from the brooming plant Dyer's Genista tinctoria L. and is widely distributed in the Fabaceae family. As an isoflavone, mammalian genistein exerts estrogen-like functions. Several biological effects of genistein have been reported in preclinical studies, such as the antioxidant, anti-inflammatory, antibacterial, and antiviral activities, the effects of angiogenesis and estrogen, and the pharmacological activities on diabetes and lipid metabolism. The purpose of this review is to provide up-to-date evidence of preclinical pharmacological activities with mechanisms of action, bioavailability, and clinical evidence of genistein. The literature was researched using the most important keyword "genistein" from the PubMed, Science, and Google Scholar databases, and the taxonomy was validated using The Plant List. Data were also collected from specialized books and other online resources. The main positive effects of genistein refer to the protection against cardiovascular diseases and to the decrease of the incidence of some types of cancer, especially breast cancer. Although the mechanism of protection against cancer involves several aspects of genistein metabolism, the researchers attribute this effect to the similarity between the structure of soy genistein and that of estrogen. This structural similarity allows genistein to displace estrogen from cellular receptors, thus blocking their hormonal activity. The pharmacological activities resulting from the experimental studies of this review support the traditional uses of genistein, but in the future, further investigations are needed on the efficacy, safety, and use of nanotechnologies to increase bioavailability and therapeutic efficacy.
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Affiliation(s)
- Javad Sharifi-Rad
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Cristina Quispe
- Facultad de Ciencias de la Salud, Universidad Arturo Prat, Avda. Arturo Prat 2120, Iquique 1110939, Chile
| | - Muhammad Imran
- University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Anbar-, 23561 Khyber Pakhtunkhwa, Pakistan
| | - Muhammad Nadeem
- Department of Environmental Sciences, COMSATS Institute of Information Technology, Vehari-, Pakistan
| | | | - Bashir Ahmad
- Center of Biotechnology and Microbiology, University of Peshawar, Peshawar-, 25120 KPK, Pakistan
| | - Muhammad Atif
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72341, Saudi Arabia
| | | | - Oksana Sytar
- Department of Plant Biology Department, Institute of Biology, Taras Shevchenko National University of Kyiv, Volodymyrska Str., 64, Kyiv 01033, Ukraine
- Department of Plant Physiology, Slovak University of Agriculture, A. Hlinku 2, 94976 Nitra, Slovakia
| | - Oxana Mihailovna Zhilina
- Department of Organic Chemistry, Pyatigorsk Medical-Pharmaceutical Institute (PMPI), Branch of Volgograd State Medical University, Ministry of Health of Russia, Pyatigorsk 357532, Russia
| | - Ekaterina Robertovna Garsiya
- Department of Pharmacognosy, Botany and Technology of Phytopreparations, Pyatigorsk Medical-Pharmaceutical Institute (PMPI), Branch of Volgograd State Medical University, Ministry of Health of Russia, Pyatigorsk 357532, Russia
| | - Antonella Smeriglio
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Italy
| | - Domenico Trombetta
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Italy
| | - Daniel Gabriel Pons
- Grupo Multidisciplinar de Oncología Traslacional (GMOT), Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears (UIB), Instituto de Investigación Sanitaria Illes Balears (IdISBa), Palma 07122, Spain
| | - Miquel Martorell
- Department of Nutrition and Dietetics, Faculty of Pharmacy, University of Concepción, Concepción 4070386, Chile
- Unidad de Desarrollo Tecnológico, Universidad de Concepción UDT, Concepción 4070386, Chile
| | - Susana M Cardoso
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Ahmad Faizal Abdull Razis
- Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400, UPM Serdang, Selangor, Malaysia
- Natural Medicines and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
| | - Usman Sunusi
- Natural Medicines and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
- Department of Biochemistry, Bayero University Kano, PMB 3011 Kano, Nigeria
| | - Ramla Muhammad Kamal
- Natural Medicines and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
- Department of Pharmacology, Federal University Dutse, PMB 7156 Dutse Jigawa State, Nigeria
| | - Lia Sanda Rotariu
- Banat's University of Agricultural Sciences and Veterinary Medicine "King Michael I of Romania" from Timisoara, Romania
| | - Monica Butnariu
- Banat's University of Agricultural Sciences and Veterinary Medicine "King Michael I of Romania" from Timisoara, Romania
| | - Anca Oana Docea
- Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Daniela Calina
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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27
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Liu L, Guo P, Wang P, Zheng S, Qu Z, Liu N. The Review of Anti-aging Mechanism of Polyphenols on Caenorhabditis elegans. Front Bioeng Biotechnol 2021; 9:635768. [PMID: 34327192 PMCID: PMC8314386 DOI: 10.3389/fbioe.2021.635768] [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: 11/30/2020] [Accepted: 06/07/2021] [Indexed: 12/11/2022] Open
Abstract
Micronutrients extracted from natural plants or made by biological synthesis are widely used in anti-aging research and applications. Among more than 30 effective anti-aging substances, employing polyphenol organic compounds for modification or delaying of the aging process attracts great interest because of their distinct contribution in the prevention of degenerative diseases, such as cardiovascular disease and cancer. There is a profound potential for polyphenol extracts in the research of aging and the related diseases of the elderly. Previous studies have mainly focused on the properties of polyphenols implicated in free radical scavenging; however, the anti-oxidant effect cannot fully elaborate its biological functions, such as neuroprotection, Aβ protein production, ion channel coupling, and signal transduction pathways. Caenorhabditis elegans (C. elegans) has been considered as an ideal model organism for exploring the mechanism of anti-aging research and is broadly utilized in screening for natural bioactive substances. In this review, we have described the molecular mechanisms and pathways responsible for the slowdown of aging processes exerted by polyphenols. We also have discussed the possible mechanisms for their anti-oxidant and anti-aging properties in C. elegans from the perspective of different classifications of the specific polyphenols, such as flavonols, anthocyanins, flavan-3-ols, hydroxybenzoic acid, hydroxycinnamic acid, and stilbenes.
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Affiliation(s)
- Limin Liu
- College of Public Health, Zhengzhou University, Zhengzhou, China.,Institute of Chronic Disease Risks Assessment, School of Nursing and Health, Henan University, Kaifeng, China
| | - Peisen Guo
- College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Peixi Wang
- Institute of Chronic Disease Risks Assessment, School of Nursing and Health, Henan University, Kaifeng, China
| | - Shanqing Zheng
- School of Basic Medical Sciences, Henan University, Kaifeng, China
| | - Zhi Qu
- Institute of Chronic Disease Risks Assessment, School of Nursing and Health, Henan University, Kaifeng, China
| | - Nan Liu
- College of Public Health, Zhengzhou University, Zhengzhou, China.,Institute of Chronic Disease Risks Assessment, School of Nursing and Health, Henan University, Kaifeng, China.,Institute of Environment and Health, South China Hospital, Health Science Center, Shenzhen University, Shenzhen, China
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28
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Erten F, Yenice E, Orhan C, Er B, Demirel Öner P, Defo Deeh PB, Şahin K. Genistein suppresses the inflammation and GSK-3 pathway in an animal model of spontaneous ovarian cancer. Turk J Med Sci 2021; 51:1465-1471. [PMID: 33550763 PMCID: PMC8283468 DOI: 10.3906/sag-2007-254] [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: 07/23/2020] [Accepted: 02/06/2021] [Indexed: 12/12/2022] Open
Abstract
Background/aim Numerous studies show that cancer risk is reduced by consumption of soy-based foods containing genistein, but its effects on the glycogen synthase kinase-3 pathway (GSK-3) in ovarian cancer is unknown. Therefore, we tested the properties of genistein on inflammatory biomarkers and GSK-3 signaling pathways in the ovaries of old laying hens with ovarian cancer. Materials and methods A total of 300 laying hens were distributed into three groups as follows: group 1, animals fed a standard diet (comprising 22.39 mg of genistein/kg of diet); groups 2 and 3, animals fed a standard diet reconstituted with supplementation of 400 mg or 800 mg of genistein/kg of diet, respectively. Results Genistein modulated the inflammatory biomarkers by decreasing serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) compared with control (p < 0.001). Moreover, it upregulated insulin receptor substrate-1 (p-IRS-1) and protein kinase B (p-AKT), but downregulated GSK-3α and β after treatment. It acts in a dose-dependent manner. Conclusion Genistein exhibited an anticancer effect by reducing proinflammatory biomarkers levels and inhibiting GSK-3 expression in the ovaries of old laying hens. It is a potential candidate in the chemoprevention and/or treatment of ovarian cancer.
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Affiliation(s)
- Füsun Erten
- Division of Biology, Faculty of Science, Fırat University, Elazığ, Turkey
| | - Engin Yenice
- Department of Animal Nutrition, Faculty of Agriculture, Ankara University, Ankara, Turkey
| | - Cemal Orhan
- Department of Animal Nutrition, Faculty of Veterinary Medicine, Fırat University, Elazığ, Turkey
| | - Beşir Er
- Division of Biology, Faculty of Science, Fırat University, Elazığ, Turkey
| | - Pınar Demirel Öner
- Department of Microbiology, Education and Research Hospital, Elazığ, Turkey
| | | | - Kazım Şahin
- Department of Animal Nutrition, Faculty of Veterinary Medicine, Fırat University, Elazığ, Turkey
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Marmitt DJ, Bitencourt S, da Silva GR, Rempel C, Goettert MI. Traditional plants with antioxidant properties in clinical trials-A systematic review. Phytother Res 2021; 35:5647-5667. [PMID: 34165846 DOI: 10.1002/ptr.7202] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 05/20/2021] [Accepted: 06/08/2021] [Indexed: 01/08/2023]
Abstract
There is a trend toward the use of natural substances present in plants and vegetables. In general, foods rich in antioxidants are complex matrices; therefore, understanding its absorption effects is extremely relevant to know its bioactive potential. Thus, this systematic review focused on clinical trials involving plants (or compounds) registered on the National List of Medicinal Plants of Interest to the Unified Health System (RENISUS) with antioxidant properties. Following the reporting guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyzes studies of interest indexed in the PubMed and ClinicalTrials.gov databases were analyzed. Of the 59 clinical trials found, Allium sativum and Curcuma longa are the plant species with the highest percentage of clinical research. Prevention/attenuation of oxidative stress was one of the main antioxidant mechanisms indicated in the studies. The most tested compounds of the RENISUS plants in clinical trials were curcumin and soy isoflavone. In this review, we selected studies in advanced stages that highlight plants' value in optimizing antioxidant status; however, even with high-quality studies, it is not prudent to overstate the clinical efficacy of these plants.
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Affiliation(s)
- Diorge Jônatas Marmitt
- Programa de Pós-graduação em Biotecnologia, Universidade do Vale do Taquari (Univates), Lajeado, RS, Brazil
| | - Shanna Bitencourt
- Programa de Pós-graduação em Biotecnologia, Universidade do Vale do Taquari (Univates), Lajeado, RS, Brazil
| | | | - Claudete Rempel
- Programa de Pós-graduação em Ambiente e Desenvolvimento/Programa de Pós-graduação em Sistemas Ambientais Sustentáveis, Universidade do Vale do Taquari (Univates), Lajeado, RS, Brazil
| | - Márcia Inês Goettert
- Programa de Pós-graduação em Biotecnologia, Universidade do Vale do Taquari (Univates), Lajeado, RS, Brazil
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30
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Pharmacological Protection against Ischemia-Reperfusion Injury by Regulating the Nrf2-Keap1-ARE Signaling Pathway. Antioxidants (Basel) 2021; 10:antiox10060823. [PMID: 34063933 PMCID: PMC8224095 DOI: 10.3390/antiox10060823] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 05/11/2021] [Accepted: 05/15/2021] [Indexed: 12/11/2022] Open
Abstract
Ischemia/reperfusion (I/R) injury is associated with substantial clinical implications, including a wide range of organs such as the brain, kidneys, lungs, heart, and many others. I/R injury (IRI) occurs due to the tissue injury following the reestablishment of blood supply to ischemic tissues, leading to enhanced aseptic inflammation and stimulation of oxidative stress via reactive oxygen and nitrogen species (ROS/RNS). Since ROS causes membrane lipids’ peroxidation, triggers loss of membrane integrity, denaturation of proteins, DNA damage, and cell death, oxidative stress plays a critical part in I/R pathogenesis. Therefore, ROS regulation could be a promising therapeutic strategy for IRI. In this context, Nrf2 (NF-E2-related factor 2) is a transcription factor that regulates the expression of several factors involved in the cellular defense against oxidative stress and inflammation, including heme oxygenase-1 (HO-1). Numerous studies have shown the potential role of the Nrf2/HO-1 pathway in IRI; thus, we will review the molecular aspects of Nrf2/Kelch-like ECH-associated protein 1 (Keap1)/antioxidant response element (ARE) signaling pathway in I/R, and we will also highlight the recent insights into targeting this pathway as a promising therapeutic strategy for preventing IRI.
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31
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Marmitt DJ, Goettert MI, Rempel C. Compounds of plants with activity against SARS-CoV-2 targets. Expert Rev Clin Pharmacol 2021; 14:623-633. [PMID: 33706626 PMCID: PMC8022338 DOI: 10.1080/17512433.2021.1903317] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 03/11/2021] [Indexed: 02/06/2023]
Abstract
INTRODUCTION The COVID-19 global pandemic is a public health emergency due to its high virulence and mortality. Many vaccine development studies at clinical trials are currently conducted to combat SARS-CoV-2. Plants are a rich source of phytochemicals with different biological activities, including antiviral activities, which are the focus of many studies. AREAS COVERED This review shows compounds of traditional plants listed on RENISUS list have therapeutic properties against SARS-CoV-2 targets. EXPERT OPINION The rise of new variants, more pathogenic and virulent, impacts in the increase of mortality from SARS-CoV-2 infection, and thus, the control of the outbreaks of disease remains a global challenge. Other's drug and vaccines development is an essential element in controlling SARS-COV-2. Therefore, it is imperative that approach to tackle this pandemic has to be solidly evidence-informed. It should be noticed that the immune system does play critical roles in fighting viruses. Studies show that T cells levels decreased continuously as the disease progressed. T cell-mediated cellular immune response, probably by immunological memory, is essential for direct virus eradication after infection whilst B cells functions in producing antibodies that neutralize virus.But, have distinct patterns of T cell response exist in different patients, suggesting the possibility of distinct clinical approaches. Efforts are concentrated to elucidate the underlying immunological mechanisms in SARS-CoV-2 pathogenesis and progression for better design of diagnostic, therapeutic and preventive strategies. We seek to identify biomolecules with the potential to act in biomarkers that predict how severe the disease can get. But it is important to warn that the plants that produce the compounds mentioned here should not be used without a physician prescription. Finally, we speculate that these compounds may eventually attract the attention of physicians and researchers to perform tests in specific contexts of SARS-CoV-2 infection, and if they show positive results, be tested in Clinical trials.
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Affiliation(s)
- Diorge Jônatas Marmitt
- Programa De Pós-graduação Em Biotecnologia, Universidade Do Vale Do Taquari - Univates, Lajeado RS, Brazil
| | - Márcia Inês Goettert
- Programa De Pós-graduação Em Biotecnologia, Universidade Do Vale Do Taquari - Univates, Lajeado RS, Brazil
| | - Claudete Rempel
- Programa De Pós-graduação Em Ambiente E Desenvolvimento/Programa De Pós-graduação Em Sistemas Ambientais Sustentáveis, Universidade Do Vale Do Taquari – Univates , Lajeado RS, Brazil
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Ramachandra CJA, Cong S, Chan X, Yap EP, Yu F, Hausenloy DJ. Oxidative stress in cardiac hypertrophy: From molecular mechanisms to novel therapeutic targets. Free Radic Biol Med 2021; 166:297-312. [PMID: 33675957 DOI: 10.1016/j.freeradbiomed.2021.02.040] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Revised: 02/11/2021] [Accepted: 02/26/2021] [Indexed: 02/06/2023]
Abstract
When faced with increased workload the heart undergoes remodelling, where it increases its muscle mass in an attempt to preserve normal function. This is referred to as cardiac hypertrophy and if sustained, can lead to impaired contractile function. Experimental evidence supports oxidative stress as a critical inducer of both genetic and acquired forms of cardiac hypertrophy, a finding which is reinforced by elevated levels of circulating oxidative stress markers in patients with cardiac hypertrophy. These observations formed the basis for using antioxidants as a therapeutic means to attenuate cardiac hypertrophy and improve clinical outcomes. However, the use of antioxidant therapies in the clinical setting has been associated with inconsistent results, despite antioxidants having been shown to exert protection in several animal models of cardiac hypertrophy. This has forced us to revaluate the mechanisms, both upstream and downstream of oxidative stress, where recent studies demonstrate that apart from conventional mediators of oxidative stress, metabolic disturbances, mitochondrial dysfunction and inflammation as well as dysregulated autophagy and protein homeostasis contribute to disease pathophysiology through mechanisms involving oxidative stress. Importantly, novel therapeutic targets have been identified to counteract oxidative stress and attenuate cardiac hypertrophy but more interestingly, the repurposing of drugs commonly used to treat metabolic disorders, hypertension, peripheral vascular disease, sleep disorders and arthritis have also been shown to improve cardiac function through suppression of oxidative stress. Here, we review the latest literature on these novel mechanisms and intervention strategies with the aim of better understanding the complexities of oxidative stress for more precise targeted therapeutic approaches to prevent cardiac hypertrophy.
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Affiliation(s)
- Chrishan J A Ramachandra
- National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore; Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore.
| | - Shuo Cong
- National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore; Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore; Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - Xavier Chan
- National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore; Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore; Faculty of Science, National University of Singapore, Singapore
| | - En Ping Yap
- National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore; Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore; Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - Fan Yu
- National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore; Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore; Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - Derek J Hausenloy
- National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore; Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore; Yong Loo Lin School of Medicine, National University Singapore, Singapore; The Hatter Cardiovascular Institute, University College London, London, UK; Cardiovascular Research Center, College of Medical and Health Sciences, Asia University, Taiwan
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Yu G, Liu Y, Ou W, Dai J, Ai Q, Zhang W, Mai K, Zhang Y. The protective role of daidzein in intestinal health of turbot (Scophthalmus maximus L.) fed soybean meal-based diets. Sci Rep 2021; 11:3352. [PMID: 33558631 PMCID: PMC7870896 DOI: 10.1038/s41598-021-82866-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 01/25/2021] [Indexed: 12/14/2022] Open
Abstract
Soybean meal-induced enteropathy (SBMIE) is prevalent in aquaculture. The aim of this study is to evaluate the role of daidzein on SBMIE of juvenile turbot (Scophthalmus maximus L.) by feeding with fish meal diet (FM), soybean meal diet (SBM, 40% fish meal protein in FM replaced by soybean meal protein) and daidzein diet (DAID, 40 mg/kg daidzein supplemented to SBM) for 12 weeks. We found that daidzein supplementation elevated the gene expression of anti-inflammatory cytokine TGF-β, decreased gene expression of pro-inflammatory cytokines TNF-α and signal molecules p38, JNK and NF-κB. SBM up-regulated the genes expression related to oxidative stress and apoptosis, but dietary daidzein restored it to the similar level with that in FM group. Moreover, dietary daidzein up-regulated gene expression of tight junction protein, and modified the intestinal microbial profiles with boosted relative abundance of phylum Proteobacteria and Deinococcus-Thermus, genera Sphingomonas and Thermus, species Lactococcus lactis, and decreased abundance of some potential pathogenic bacteria. In conclusion, dietary daidzein could ameliorate SBM-induced intestinal inflammatory response, oxidative stress, mucosal barrier injury and microbiota community disorder of turbot. Moreover, p38, JNK and NF-κB signaling might be involved in the anti-inflammatory process of daidzein, and daidzein itself might act as an antioxidant to resist SBM-induced oxidative damage.
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Affiliation(s)
- Guijuan Yu
- The Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture), and the Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, Qingdao, China
| | - Yang Liu
- The Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture), and the Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, Qingdao, China
| | - Weihao Ou
- The Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture), and the Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, Qingdao, China
| | - Jihong Dai
- The Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture), and the Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, Qingdao, China
| | - Qinghui Ai
- The Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture), and the Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, Qingdao, China
| | - Wenbing Zhang
- The Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture), and the Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, Qingdao, China
| | - Kangsen Mai
- The Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture), and the Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, Qingdao, China
- Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Yanjiao Zhang
- The Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture), and the Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, Qingdao, China.
- Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.
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Clifford T, Acton JP, Cocksedge SP, Davies KAB, Bailey SJ. The effect of dietary phytochemicals on nuclear factor erythroid 2-related factor 2 (Nrf2) activation: a systematic review of human intervention trials. Mol Biol Rep 2021; 48:1745-1761. [PMID: 33515348 PMCID: PMC7925463 DOI: 10.1007/s11033-020-06041-x] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 11/28/2020] [Indexed: 01/06/2023]
Abstract
We conducted a systematic review of human trials examining the effects of dietary phytochemicals on Nrf2 activation. In accordance with the PRISMA guidelines, Medline, Embase and CAB abstracts were searched for articles from inception until March 2020. Studies in adult humans that measured Nrf2 activation (gene or protein expression changes) following ingestion of a phytochemical, either alone or in combination were included. The study was pre-registered on the Prospero database (Registration Number: CRD42020176121). Twenty-nine full-texts were retrieved and reviewed for analysis; of these, eighteen were included in the systematic review. Most of the included participants were healthy, obese or type 2 diabetics. Study quality was assessed using the Cochrane Collaboration Risk of Bias Assessment tool. Twelve different compounds were examined in the included studies: curcumin, resveratrol and sulforaphane were the most common (n = 3 each). Approximately half of the studies reported increases in Nrf2 activation (n = 10); however, many were of poor quality and had an unclear or high risk of bias. There is currently limited evidence that phytochemicals activate Nrf2 in humans. Well controlled human intervention trials are needed to corroborate the findings from in vitro and animal studies.
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Affiliation(s)
- Tom Clifford
- School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, LE11 3TU, UK.
| | - Jarred P Acton
- School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, LE11 3TU, UK
| | - Stuart P Cocksedge
- School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, LE11 3TU, UK
| | - Kelly A Bowden Davies
- Department of Sport and Exercise Sciences, Manchester Metropolitan University, Manchester, M15 6BH, UK
| | - Stephen J Bailey
- School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, LE11 3TU, UK
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Effects of soy intake on circulating levels of TNF-α and interleukin-6: a systematic review and meta-analysis of randomized controlled trials. Eur J Nutr 2021; 60:581-601. [PMID: 33399974 DOI: 10.1007/s00394-020-02458-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Accepted: 12/07/2020] [Indexed: 12/29/2022]
Abstract
PURPOSE Pro-inflammatory mediators, including serum tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), can be used as biomarkers to indicate or monitor disease. This study was designed to ascertain the effects of soy products on TNF-α and IL-6 levels. METHODS PubMed, EMBASE, Science Direct, Web of Science, Google Scholar and the Cochrane Central Register of Controlled Trials were searched to November 2019 for RCTs around the effects of soy-based products on TNF-α and IL-6. A random effects model was used to calculate overall effect size. RESULTS In total, 29 eligible publications were considered in the present systematic review, of which 25 were included in this meta-analysis. The overall effect of soy products on TNF-α and IL-6 levels failed to reach statistical significance (MD = - 0.07; 95% CI - 0.22-0.09; I2 50.9; MD = 0.03; 95% CI - 0.07-0.14; I2 42.1, respectively). According to a subgroup analysis, natural soy products led to a reduction in TNF-α concentration compared with processed soy products (MD = - 0.32; 95% CI - 0.45 to - 0.19; I2 0.0). Moreover, IL-6 reduction was stronger in participants who were affected by different diseases (MD = - 0.04; 95% CI - 0.07 to - 0.02; I2 0.0). CONCLUSIONS A review of RCTs published to November 2019 found that natural soy products are effective in lowering TNF-α levels. While the beneficial effects on reduction of IL-6 appeared stronger in individuals affected by different diseases, this finding cannot be generalized to all individuals affected by different diseases.
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Abstract
Heart failure is a worldwide pandemic influencing 26 million individuals worldwide and is expanding. Imbalanced redox homeostasis in cardiac cells alters the structure and function of the cells, which leads to contractile dysfunction, myocardial hypertrophy, and fibrosis in chronic heart failure. Various targets and agents acting on these such as siRNA, miRNA, interleukin-1, opioids, vasodilators, and SGLT2 inhibitors are being evaluated for heart failure, and nuclear factor erythroid 2-related factor 2 (NRF2) is one of them. NRF2 is a master transcription factor which is expressed in most of the tissues and exhibits a major role in amplification of the antioxidant pathways associated with the enzymes present in myocardium. Increased ROS generation and PI3K-Akt signaling can activate the receptor NRF2. Various in vitro and in vivo and few clinical studies suggested NRF2 may possess a potential for targeting oxidative stress-induced cardiovascular diseases including heart failures. All these studies collectively propose that upregulation of NRF2 will attenuate the increase in hemodynamic stress and provide beneficial role in cardiovascular diseases. The current review shall familiarize readers about the regulations and functions of NRF2. We have also discussed the current evidences suggesting beneficial role of NRF2 activators in heart failure. Graphical abstract.
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The mKATP Channels and protein-kinase C Are Involved in the Cardioprotective Effects of Genistein on Estrogen-Deficient Rat Hearts Exposed to Ischemia/Reperfusion: Energetic Study. J Cardiovasc Pharmacol 2020; 75:460-474. [PMID: 32195757 DOI: 10.1097/fjc.0000000000000816] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Estrogenic deficiency is considered a risk of coronary disease in women. The phytoestrogen genistein could be a safe preventive strategy. The first aim of this work was to validate a model of cardiac stunning in which natural estrogenic deficiency rats, ie, adult young male (YM) and aged female (AgF), are compared with young female rats (YF). The second aim was to study whether the in vivo administration of genistein prevents the stunning in estrogenic deficiency rats. The third aim was to evaluate whether in our estrogenic deficiency model exists a synergy between genistein and estradiol. The fourth aim was to characterize the underlying mechanisms of genistein. Stunning was induced by ischemia/reperfusion (I/R) in isolated hearts inside a calorimeter. The left ventricular pressure (P) and total heat rate (Ht) were simultaneously measured, while diastolic contracture and muscle economy (P/Ht) were calculated. During R, P/Ht and P recovered less in AgF and YM than in YF rat hearts. Genistein through i.p. (GST-ip) improved P and P/Ht in AgF and YM, but not in YF. In YM, the cardioprotections of GST-ip and estradiol were synergistic. After ischemia, GST-ip increased SR Ca leak causing diastolic contracture. The GST-ip cardioprotection neither was affected by blockade of PI3K-Akt, NO synthases, or phosphatases, but it was sensitive to blockade of protein-kinase C and mKATP channels. Results suggest that (1) estrogenic deficiency worsens cardiac stunning, (2) GST-ip was more cardioprotective in estrogenic deficiency and synergistic with estradiol, and (3) cardioprotection of GST-ip depends on the protein-kinase C and mKATP channel pathway activation.
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Morvaridzadeh M, Nachvak SM, Agah S, Sepidarkish M, Dehghani F, Rahimlou M, Pizarro AB, Heshmati J. Effect of soy products and isoflavones on oxidative stress parameters: A systematic review and meta-analysis of randomized controlled trials. Food Res Int 2020; 137:109578. [PMID: 33233189 DOI: 10.1016/j.foodres.2020.109578] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 06/26/2020] [Accepted: 07/18/2020] [Indexed: 12/12/2022]
Abstract
Soy products and isoflavones intake have been shown to exert antioxidant effects. There are several randomized control trials (RCTs) that evaluated the effect of soy products intake on oxidative stress (OS) parameters. The aim of the present systematic review and meta-analysis was to summarize the results of RCTs evaluating the effect of soy products and isoflavones intake on OS parameters. Randomized trials that assessed the effect of soy products and isoflavones intake on OS parameters in adults were identified through searching in electronic databases: Cochrane clinical trial center, Embase, PubMed, Scopus, and Web of Sciences up to April 2020. Random effects model was used to calculate the effects sizes of soy intake on OS parameters. Twenty-four trials with 1,852 participants were eligible and were included in the meta-analysis which measured OS parameters. Soy intake compared to control group significantly reduced MDA levels (SMD: -0.53; 95% CI: -0.86, -0.19; I2 = 88.3%), increased GSH levels (SMD: 0.51; 95% CI: 0.13, 0.88; I2 = 72.4%), SOD activity (SMD: 0.53; 95% CI: 0.08, 0.99; I2 = 84.1%), TAC (SMD: 0.54; 95% CI: 0.27, 0.82; I2 = 49.3%) and TRAP (SMD: 1.74; 95% CI: 0.82, 2.65; I2 = 81.3%) significantly compared to control group. Soy products and isoflavones intake are effective in improving OS parameters in adults compared with controls; thus, it could be a valuable advise to control OS progress in chronic diseases.
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Affiliation(s)
- Mojgan Morvaridzadeh
- Department of Nutritional Science, School of Nutritional Science and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Seyed Mostafa Nachvak
- Department of Nutritional Science, School of Nutritional Science and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Shahram Agah
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mahdi Sepidarkish
- Department of Biostatistics and Epidemiology, School of Public Health, Babol University of Medical Sciences, Babol, Iran
| | - Fereshteh Dehghani
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Mehran Rahimlou
- Nutrition Department, Faculty of Paramedicine, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran
| | - Ana Beatriz Pizarro
- Department of Epidemiology and Biostatistics, Pontificia Universidad Javeriana, Bogotá, Colombia.
| | - Javad Heshmati
- Department of Nutritional Science, School of Nutritional Science and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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Silva DVTD, Baião DDS, Ferreira VF, Paschoalin VMF. Betanin as a multipath oxidative stress and inflammation modulator: a beetroot pigment with protective effects on cardiovascular disease pathogenesis. Crit Rev Food Sci Nutr 2020; 62:539-554. [PMID: 32997545 DOI: 10.1080/10408398.2020.1822277] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Oxidative stress is a common physiopathological condition enrolled in risk factors for cardiovascular diseases. Individuals in such a redox imbalance status present endothelial dysfunctions and inflammation, reaching the onset of heart disease. Phytochemicals are able to attenuate the main mechanisms of oxidative stress and inflammation and should be considered as supportive therapies to manage risk factors for cardiovascular diseases. Beetroot (Beta vulgaris L.) is a rich source of bioactive compounds, including betanin (betanidin-5-O-β-glucoside), a pigment displaying the potential to alleviate oxidative stress and inflammantion, as previously demonstrated in preclinical trials. Betanin resists gastrointestinal digestion, is absorbed by the epithelial cells of intestinal mucosa and reaches the plasma in its active form. Betanin displays free-radical scavenger ability through hydrogen or electron donation, preserving lipid structures and LDL particles while inducing the transcription of antioxidant genes through the nuclear factor erythroid-2-related factor 2 and, simultaneously, suppressing the pro-inflammatory nuclear factor kappa-B pathways. This review discusses the anti-radical and gene regulatory cardioprotective activities of betanin in the pathophysiology of endothelial damage and atherogenesis, the main conditions for cardiovascular disease. In addition, betanin influences on these multipath cellular signals and aiding in reducing cardiovascular disorders is proposed.
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Affiliation(s)
| | - Diego Dos Santos Baião
- Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
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Natural Drugs as a Treatment Strategy for Cardiovascular Disease through the Regulation of Oxidative Stress. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:5430407. [PMID: 33062142 PMCID: PMC7537704 DOI: 10.1155/2020/5430407] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 09/02/2020] [Accepted: 09/09/2020] [Indexed: 02/07/2023]
Abstract
Oxidative stress (OS) refers to the physiological imbalance between oxidative and antioxidative processes leading to increased oxidation, which then results in the inflammatory infiltration of neutrophils, increased protease secretion, and the production of a large number of oxidative intermediates. Oxidative stress is considered an important factor in the pathogenesis of cardiovascular disease (CVD). At present, active components of Chinese herbal medicines (CHMs) have been widely used for the treatment of CVD, including coronary heart disease and hypertension. Since the discovery of artemisinin for the treatment of malaria by Nobel laureate Youyou Tu, the therapeutic effects of active components of CHM on various diseases have been widely investigated by the medical community. It has been found that various active CHM components can regulate oxidative stress and the circulatory system, including ginsenoside, astragaloside, and resveratrol. This paper reviews advances in the use of active CHM components that modulate oxidative stress, suggesting potential drugs for the treatment of various CVDs.
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Yu Z, Yang L, Deng S, Liang M. Daidzein ameliorates LPS-induced hepatocyte injury by inhibiting inflammation and oxidative stress. Eur J Pharmacol 2020; 885:173399. [PMID: 32712091 DOI: 10.1016/j.ejphar.2020.173399] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 07/21/2020] [Accepted: 07/22/2020] [Indexed: 02/06/2023]
Abstract
Endotoxin-induced acute liver injury (ALI) is a severe disease associated with a poor prognosis. Therefore, it is urgent to discover new effective therapies to prevent ALI. Daidzein, extracted from leguminous plants, possess anti-inflammatory and antioxidative bioactivities. However, little is known about whether daidzein could attenuate lipopolysaccharide (LPS)-induced ALI. We investigated the effects of daidzein on hepatocyte injury and its underlying mechanisms. In LPS-induced hepatocyte supernatant, 100 μM daidzein decreased ALT and AST expression levels by 49.3% ± 5.6% and 39.3% ± 3.5%, respectively, with no cytotoxicity. In addition, the expression of inflammatory factors, including interleukin-1β (IL-lβ), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were decreased by 100 μM daidzein (73.8% ± 5.3%, 58.8 ± 9.0% and 55.5% ± 7.2%, respectively) in LPS-treated hepatocytes. Western blot analysis showed that daidzein inhibited LPS-induced p-ERK1/2, p-IκBα and p-p65 expression levels. Moreover, 100 μM daidzein reduced the LPS-induced production of Reactive oxygen species by 23.9 ± 7.8% and increased SOD activity by 88.4% ± 18.9% by downregulating Keap-1 and upregulating Nrf2 expression. In conclusion, these data indicate that daidzein ameliorates LPS-induced hepatocyte injury by inhibiting inflammation and oxidative stress.
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Affiliation(s)
- Zuying Yu
- Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Liu Yang
- Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shan Deng
- Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Minglu Liang
- Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Rizzo G. The Antioxidant Role of Soy and Soy Foods in Human Health. Antioxidants (Basel) 2020; 9:antiox9070635. [PMID: 32708394 PMCID: PMC7402135 DOI: 10.3390/antiox9070635] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 07/08/2020] [Accepted: 07/16/2020] [Indexed: 02/07/2023] Open
Abstract
Oxidative stress seems to play a role in many chronic diseases, such as cardiovascular diseases, diabetes, and some cancers. Research is always looking for effective approaches in the prevention and treatment of these pathologies with safe strategies. Given the central role of nutrition, the identification of beneficial healthy foods can be the best key to having a safe and at the same time effective approach. Soy has always aroused great scientific interest but often this attention is galvanized by the interaction with estrogen receptors and related consequences on health. However, soy, soy foods, and soy bioactive substances seem to have antioxidant properties, suggesting their role in quenching reactive oxygen species, although it was frequently mentioned but not studied in depth. The purpose of this review is to summarize the scientific evidence of the antioxidant properties of soy by identifying the human clinical trials available in the literature. A total of 58 manuscripts were individuated through the literature search for the final synthesis. Soy bioactive substances involved in redox processes appear to be multiple and their use seems promising. Other larger clinical trials with adequate standardization and adequate choice of biomarkers will fill the gap currently existing on the suggestive role of soy in antioxidant mechanisms.
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Affiliation(s)
- Gianluca Rizzo
- Independent Researcher, Via Venezuela 66, 98121 Messina, Italy
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Isoflavone-enriched whole soy milk powder stimulates osteoblast differentiation. Journal of Food Science and Technology 2020; 58:595-603. [PMID: 33568853 DOI: 10.1007/s13197-020-04572-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Revised: 05/27/2020] [Accepted: 06/10/2020] [Indexed: 10/24/2022]
Abstract
Functional foods with high nutritive values and potential therapeutic potential is a prerequisite for today's ailing world. Soybeans exert beneficial effects on human health. It contains plentiful polyunsaturated fatty acids and dietary fibers along with several isoflavonoids having bioactivity for improving health. Recent studies have shown that soybean isoflavones can have a positive effect on bone growth. The current study was designed to observe any impact of isoflavone-enriched soy milk powder (I-WSM) on inducing osteogenic properties at cellular and molecular levels. Precisely, we have evaluated the effect of I-WSM on the bone differentiation process. Our results show that I-WSM has the ability to stimulate osteogenic properties in osteoblasts both at the initial and terminal stages of differentiation. Treatment of I-WSM on osteoblasts demonstrates the inductive effect on the expression of osteogenic transcriptional factors like Runx2 and Osterix. Moreover, I-WSM increased the expression of the extracellular matrix protein osteocalcin, required for the formation of scaffold for bone mineralization. The estrogen signaling pathway was utilized by I-WSM to induce osteogenic activity. Taken together, here we report the cellular and molecular events mediated by I-WSM to exert an osteogenic effect in osteoblasts, which will help to understand its mechanism of action and project it as a remedy for the bone-related disease. Taken together, I-WSM has the ability to exert the osteogenic effect in osteoblasts via the estrogen signaling pathway and thus might be projected as a remedy for a bone-related disease like osteoporosis.
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Abstract
Soybeans are among the most popular foods worldwide, and intake of soy-containing foods has been associated with many health benefits in part because of it structure similar to estrogen. Epidemiologic studies have demonstrated that soy consumption improves serum profiles of hypercholesterolemic patients. Several studies have also indicated an inverse relationship between the consumption of soy isoflavones and the incidence of cardiovascular diseases (CVD). Soy is a rich dietary source of isoflavones. The main soy isoflavones are daidzein and genistein; equol, another isoflavone and a major intestinal bacterial metabolite of daidzein, is generated by enterobacterial effects. Many isoflavones have antioxidative effects and anti-inflammatory actions, as well as induce nitric oxide production to maintain a healthy endothelium and prevent endothelial cell dysfunction. These effects may limit the development of atherosclerosis and CVD and restore healthy endothelial function in altered endothelia. Although the evidence supporting the benefits of soy isoflavones in CVD prevention continues to increase, the association between soy isoflavones and disease is not fully understood. This review summarized recent progress in identifying the preventive mechanisms of action of dietary soybean isoflavones on vascular endothelial cells. Furthermore, it describes the beneficial roles that these isoflavones may have on endothelial dysfunction-related atherosclerosis.
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The effect of soy isoflavones on arterial stiffness: a systematic review and meta-analysis of randomized controlled trials. Eur J Nutr 2020; 60:603-614. [PMID: 32529287 DOI: 10.1007/s00394-020-02300-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Accepted: 06/05/2020] [Indexed: 01/05/2023]
Abstract
PURPOSE Some but not all randomized controlled trials (RCTs) of soy isoflavones showed their beneficial effect on arterial stiffness, a predictor of cardiovascular events, dementia, and all-cause mortality, independent of traditional risk factors. To test the hypothesis that supplementation of soy isoflavones reduces arterial stiffness, we performed a systematic review and meta-analysis of RCTs of soy isoflavones on arterial stiffness. METHODS The protocol of this systematic review was registered with PROSPERO (CRD42019126128) and written in accordance with PRISMA. The PubMed, Embase, and clinicaltrials.gov databases were searched using the following criteria: human subjects, soy isoflavones as intervention, and arterial stiffness as primary outcome. A random-effects meta-analysis was used to pool estimates across studies. Standardized mean difference (SMD) was used to synthesize quantitative results. RESULTS Among 998 articles retrieved, 8 articles met our criteria. Duration of intervention was relatively short (maximum of 12 weeks). Outcome measurements extracted were pulse wave velocity (PWV), systemic arterial compliance (SAC), augmentation index (AI), and cardio-ankle vascular index (CAVI). Soy isoflavones reduced arterial stiffness compared to placebo (standardized mean difference - 0.33, 95% confidence interval - 0.47, - 0.19). Subgroup analyses showed no difference between treatment effects for intervention duration (< 6 weeks vs. ≥ 6 weeks) or gender (women only vs. men only vs. combined). Sensitivity analysis showed no difference in the effect of soy isoflavones between PWV, CAVI, SAC, and AI. CONCLUSION Supplementation of soy isoflavones reduced arterial stiffness. Longer duration trials with larger number of participants are warranted.
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A Dual Face of APE1 in the Maintenance of Genetic Stability in Monocytes: An Overview of the Current Status and Future Perspectives. Genes (Basel) 2020; 11:genes11060643. [PMID: 32545201 PMCID: PMC7349382 DOI: 10.3390/genes11060643] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 06/05/2020] [Accepted: 06/08/2020] [Indexed: 12/24/2022] Open
Abstract
Monocytes, which play a crucial role in the immune system, are characterized by an enormous sensitivity to oxidative stress. As they lack four key proteins responsible for DNA damage response (DDR) pathways, they are especially prone to reactive oxygen species (ROS) exposure leading to oxidative DNA lesions and, consequently, ROS-driven apoptosis. Although such a phenomenon is of important biological significance in the regulation of monocyte/macrophage/dendritic cells’ balance, it also a challenge for monocytic mechanisms that have to provide and maintain genetic stability of its own DNA. Interestingly, apurinic/apyrimidinic endonuclease 1 (APE1), which is one of the key proteins in two DDR mechanisms, base excision repair (BER) and non-homologous end joining (NHEJ) pathways, operates in monocytic cells, although both BER and NHEJ are impaired in these cells. Thus, on the one hand, APE1 endonucleolytic activity leads to enhanced levels of both single- and double-strand DNA breaks (SSDs and DSBs, respectively) in monocytic DNA that remain unrepaired because of the impaired BER and NHEJ. On the other hand, there is some experimental evidence suggesting that APE1 is a crucial player in monocytic genome maintenance and stability through different molecular mechanisms, including induction of cytoprotective and antioxidant genes. Here, the dual face of APE1 is discussed.
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Zhang P, Du H, Wang J, Pu Y, Yang C, Yan R, Yang H, Cheng H, Yu D. Multiplex CRISPR/Cas9-mediated metabolic engineering increases soya bean isoflavone content and resistance to soya bean mosaic virus. PLANT BIOTECHNOLOGY JOURNAL 2020; 18:1384-1395. [PMID: 31769589 PMCID: PMC7206993 DOI: 10.1111/pbi.13302] [Citation(s) in RCA: 115] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Accepted: 11/18/2019] [Indexed: 05/18/2023]
Abstract
Isoflavonoids, which include a variety of secondary metabolites, are derived from the phenylpropanoid pathway and are distributed predominantly in leguminous plants. These compounds play a critical role in plant-environment interactions and are beneficial to human health. Isoflavone synthase (IFS) is a key enzyme in isoflavonoid synthesis and shares a common substrate with flavanone-3-hydroxylase (F3H) and flavone synthase II (FNS II). In this study, CRISPR/Cas9-mediated multiplex gene-editing technology was employed to simultaneously target GmF3H1, GmF3H2 and GmFNSII-1 in soya bean hairy roots and plants. Various mutation types and frequencies were observed in hairy roots. Higher mutation efficiencies were found in the T0 transgenic plants, with a triple gene mutation efficiency of 44.44%, and these results of targeted mutagenesis were stably inherited in the progeny. Metabolomic analysis of T0 triple-mutants leaves revealed significant improvement in isoflavone content. Compared with the wild type, the T3 generation homozygous triple mutants had approximately twice the leaf isoflavone content, and the soya bean mosaic virus (SMV) coat protein content was significantly reduced by one-third after infection with strain SC7, suggesting that increased isoflavone content enhanced the leaf resistance to SMV. The isoflavone content in the seeds of T2 triple mutants was also significantly increased. This study provides not only materials for the improvement of soya bean isoflavone content and resistance to SMV but also a simple system to generate multiplex mutations in soya bean, which may be beneficial for further breeding and metabolic engineering.
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Affiliation(s)
- Peipei Zhang
- National Center for Soybean ImprovementNational Key Laboratory of Crop Genetics and Germplasm EnhancementJiangsu Collaborative Innovation Center for Modern Crop ProductionNanjing Agricultural UniversityNanjingChina
| | - Hongyang Du
- National Center for Soybean ImprovementNational Key Laboratory of Crop Genetics and Germplasm EnhancementJiangsu Collaborative Innovation Center for Modern Crop ProductionNanjing Agricultural UniversityNanjingChina
- Key Laboratory of Rice Genetic Breeding of Anhui ProvinceRice Research InstituteAnhui Academy of Agricultural ScienceHefeiChina
| | - Jiao Wang
- National Center for Soybean ImprovementNational Key Laboratory of Crop Genetics and Germplasm EnhancementJiangsu Collaborative Innovation Center for Modern Crop ProductionNanjing Agricultural UniversityNanjingChina
| | - Yixiang Pu
- National Center for Soybean ImprovementNational Key Laboratory of Crop Genetics and Germplasm EnhancementJiangsu Collaborative Innovation Center for Modern Crop ProductionNanjing Agricultural UniversityNanjingChina
| | - Changyun Yang
- National Center for Soybean ImprovementNational Key Laboratory of Crop Genetics and Germplasm EnhancementJiangsu Collaborative Innovation Center for Modern Crop ProductionNanjing Agricultural UniversityNanjingChina
| | - Rujuan Yan
- National Center for Soybean ImprovementNational Key Laboratory of Crop Genetics and Germplasm EnhancementJiangsu Collaborative Innovation Center for Modern Crop ProductionNanjing Agricultural UniversityNanjingChina
| | - Hui Yang
- National Center for Soybean ImprovementNational Key Laboratory of Crop Genetics and Germplasm EnhancementJiangsu Collaborative Innovation Center for Modern Crop ProductionNanjing Agricultural UniversityNanjingChina
- School of Life SciencesGuangzhou UniversityGuangzhouChina
| | - Hao Cheng
- National Center for Soybean ImprovementNational Key Laboratory of Crop Genetics and Germplasm EnhancementJiangsu Collaborative Innovation Center for Modern Crop ProductionNanjing Agricultural UniversityNanjingChina
| | - Deyue Yu
- National Center for Soybean ImprovementNational Key Laboratory of Crop Genetics and Germplasm EnhancementJiangsu Collaborative Innovation Center for Modern Crop ProductionNanjing Agricultural UniversityNanjingChina
- School of Life SciencesGuangzhou UniversityGuangzhouChina
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Lecerf JM, Arnoldi A, Rowland I, Trabal J, Widhalm K, Aiking H, Messina M. Soyfoods, glycemic control and diabetes. NUTR CLIN METAB 2020. [DOI: 10.1016/j.nupar.2020.02.437] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Brandes MS, Gray NE. NRF2 as a Therapeutic Target in Neurodegenerative Diseases. ASN Neuro 2020; 12:1759091419899782. [PMID: 31964153 PMCID: PMC6977098 DOI: 10.1177/1759091419899782] [Citation(s) in RCA: 167] [Impact Index Per Article: 33.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 11/26/2019] [Accepted: 12/03/2019] [Indexed: 12/13/2022] Open
Abstract
Increased reactive oxygen species production and oxidative stress have been implicated in the pathogenesis of numerous neurodegenerative conditions including among others Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Friedrich’s ataxia, multiple sclerosis, and stroke. The endogenous antioxidant response pathway protects cells from oxidative stress by increasing the expression of cytoprotective enzymes and is regulated by the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2). In addition to regulating the expression of antioxidant genes, NRF2 has also been shown to exert anti-inflammatory effects and modulate both mitochondrial function and biogenesis. This is because mitochondrial dysfunction and neuroinflammation are features of many neurodegenerative diseases as well NRF2 has emerged as a promising therapeutic target. Here, we review evidence for a beneficial role of NRF2 in neurodegenerative conditions and the potential of specific NRF2 activators as therapeutic agents.
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Affiliation(s)
- Mikah S. Brandes
- Department of Neurology, Oregon Health and Science University, Portland, OR, USA
| | - Nora E. Gray
- Department of Neurology, Oregon Health and Science University, Portland, OR, USA
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Liu ZM, Chen B, Li S, Li G, Zhang D, Ho SC, Chen YM, Ma J, Qi H, Ling WH. Effect of whole soy and isoflavones daidzein on bone turnover and inflammatory markers: a 6-month double-blind, randomized controlled trial in Chinese postmenopausal women who are equol producers. Ther Adv Endocrinol Metab 2020; 11:2042018820920555. [PMID: 32595918 PMCID: PMC7303504 DOI: 10.1177/2042018820920555] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Accepted: 03/13/2020] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Human studies have demonstrated the beneficial effects of soy or isoflavones on bone metabolism. However, conflicting data remain. Equol is the intestinal metabolite of the isoflavone daidzein. The health benefits of soy are more pronounced in equol producers than those not producing equol. This 6-month randomized controlled trial aimed to examine the effect of whole soy (soy flour) and purified daidzein on bone turnover markers (BTMs) in Chinese postmenopausal women who are equol producers. METHODS A total of 270 eligible women were randomized to either one of the three isocaloric supplements as follows: 40 g soy flour (whole soy group), 40 g low-fat milk powder + 63 mg daidzein (daidzein group), or 40 g low-fat milk powder (placebo group) given as a solid beverage daily for 6 months. The following fasting venous samples were collected at the baseline and end of the trial to analyze BTMs: serum cross-linked C-telopeptides of type I collagen, bone-specific alkaline phosphatase, osteocalcin, procollagen type I N-terminal propeptide, and 25(OH)D3. Inflammation-related biomarkers, such as serum interleukin-6, tumor necrosis factor-alpha, C-reactive protein, transferrin, and homocysteine, were also tested to explore potential mechanisms. RESULTS A total of 253 subjects validly completed the study protocol. Urinary isoflavones suggested a good compliance to the treatments. Intention-to-treat and per-protocol analyses indicated no significant difference in the 6-month or percentage changes in the parameters of bone metabolism and inflammatory markers among the three treatment groups. CONCLUSIONS Whole soy and purified daidzein at provided dosages exhibited no significant effect on the bone metabolism and inflammation levels among Chinese equol-producing postmenopausal women. TRIAL REGISTRATION ClinicalTrials.gov identifier NCT01270737.
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Affiliation(s)
| | - Bailing Chen
- Department of Spine Surgery, the First
Affiliated Hospital of Sun Yet-sen University, Guangzhou, Guangdong, PR
China
| | - Shuyi Li
- Department of Nutrition, School of Public
Health, Sun Yat-sen University (North Campus), Guangzhou, Guangdong, PR
China
| | - Guoyi Li
- Department of Nutrition, School of Public
Health, Sun Yat-sen University (North Campus), Guangzhou, Guangdong, PR
China
| | - Di Zhang
- Department of Nutrition, School of Public
Health, Sun Yat-sen University (North Campus), Guangzhou, Guangdong, PR
China
| | - Suzanne C. Ho
- Department of Epidemiology, Jockey Club School
of Public Health and Primary Care, the Chinese University of Hong Kong, New
Territories, Hong Kong
| | - Yu-ming Chen
- Department of Nutrition, School of Public
Health, Sun Yat-sen University (North Campus), Guangzhou, Guangdong, PR
China
| | - Jing Ma
- Department of Nutrition, School of Public
Health, Sun Yat-sen University (North Campus), Guangzhou, Guangdong, PR
China
| | - Huang Qi
- Department of Nutrition, School of Public
Health, Sun Yat-sen University (North Campus), Guangzhou, Guangdong, PR
China
| | - Wen-hua Ling
- Department of Nutrition, School of Public
Health, Sun Yat-sen University (North Campus), Guangzhou, Guangdong, PR
China
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