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Yuan L, Liu J, Xiao S, Wei J, Liu H, Li Y, Zuo Y, Li Y, Wang J, Li J. EGCG-Modified Bioactive Core-Shell Fibers Modulate Oxidative Stress to Synergistically Promote Vascularized Bone Regeneration. ACS Biomater Sci Eng 2025; 11:543-555. [PMID: 39743979 DOI: 10.1021/acsbiomaterials.4c01906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Oxidative stress induced by reactive oxygen species (ROS) can adversely affect tissue repair, whereas endowing biomaterials with antioxidant activity can improve the in vivo microenvironment, thereby promoting angiogenesis and osteogenesis. Accordingly, this study utilized epigallocatechin-3-gallate (EGCG), a material known for its reducing properties, oxidative self-polymerization capability, and strong binding characteristics, to modify a bioactive core-shell fibrous membrane (10RP-PG). Compared to the 10RP-PG fibrous membrane, the EGCG-modified fibrous membrane (E/10RP-PG) exhibited superior hydrophilicity, excellent cell adhesion, and compatibility. Moreover, the EGCG-modified fibrous membrane can effectively scavenge free radicals, ameliorate the local microenvironment, and foster angiogenesis (enhancing the expression of angiogenic genes in human umbilical vein endothelial cells (HUVECs) by 1.58 times and promoting vascular generation area upon subcutaneous implantation by 4.47 times). The enhancement of angiogenic activity of the E/10RP-PG fibrous membrane further promoted cartilage degeneration and absorption, as well as new bone formation, thus facilitating the repair of bone defects. This study provides a new strategy for promoting bone defect repair through the surface modification of biomaterials with an antioxidant agent, and the fabricated E/10RP-PG fibrous membranes show promise for guiding vascularized bone regeneration.
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Affiliation(s)
- Li Yuan
- Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, Chengdu 610064, PR China
| | - Jiangshan Liu
- Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, Chengdu 610064, PR China
| | - Shiqi Xiao
- Clinical Medical College & Affiliated Hospital, Chengdu University, Chengdu 610081, PR China
| | - Jiawei Wei
- The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou 646000, PR China
| | - Huan Liu
- Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, Chengdu 610064, PR China
| | - Yongzhi Li
- Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, Chengdu 610064, PR China
| | - Yi Zuo
- Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, Chengdu 610064, PR China
| | - Yubao Li
- Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, Chengdu 610064, PR China
| | - Jun Wang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610064, PR China
| | - Jidong Li
- Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, Chengdu 610064, PR China
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Manosalva C, Bahamonde C, Soto F, Leal V, Ojeda C, Cortés C, Alarcón P, Burgos RA. Linoleic Acid Induces Metabolic Reprogramming and Inhibits Oxidative and Inflammatory Effects in Keratinocytes Exposed to UVB Radiation. Int J Mol Sci 2024; 25:10385. [PMID: 39408715 PMCID: PMC11476445 DOI: 10.3390/ijms251910385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 09/20/2024] [Accepted: 09/24/2024] [Indexed: 10/20/2024] Open
Abstract
Linoleic acid (LA), the primary ω-6 polyunsaturated fatty acid (PUFA) found in the epidermis, plays a crucial role in preserving the integrity of the skin's water permeability barrier. Additionally, vegetable oils rich in LA have been shown to notably mitigate ultraviolet (UV) radiation-induced effects, including the production of reactive oxygen species (ROS), cellular damage, and skin photoaging. These beneficial effects are primarily ascribed to the LA in these oils. Nonetheless, the precise mechanisms through which LA confers protection against damage induced by exposure to UVB radiation remain unclear. This study aimed to examine whether LA can restore redox and metabolic equilibria and to assess its influence on the inflammatory response triggered by UVB radiation in keratinocytes. Flow cytometry analysis unveiled the capacity of LA to diminish UVB-induced ROS levels in HaCaT cells. GC/MS-based metabolomics highlighted significant metabolic changes, especially in carbohydrate, amino acid, and glutathione (GSH) metabolism, with LA restoring depleted GSH levels post-UVB exposure. LA also upregulated PI3K/Akt-dependent GCLC and GSS expression while downregulating COX-2 expression. These results suggest that LA induces metabolic reprogramming, protecting against UVB-induced oxidative damage by enhancing GSH biosynthesis via PI3K/Akt signaling. Moreover, it suppresses UVB-induced COX-2 expression in HaCaT cells, making LA treatment a promising strategy against UVB-induced oxidative and inflammatory damage.
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Affiliation(s)
- Carolina Manosalva
- Institute of Pharmacy, Faculty of Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile
| | - Claudio Bahamonde
- Institute of Pharmacy, Faculty of Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile
| | - Franco Soto
- Institute of Pharmacy, Faculty of Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile
| | - Vicente Leal
- Institute of Pharmacy, Faculty of Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile
| | - César Ojeda
- Institute of Pharmacy, Faculty of Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile
| | - Carmen Cortés
- Institute of Pharmacy, Faculty of Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile
| | - Pablo Alarcón
- Laboratory of Inflammation Pharmacology and Immunometabolism, Institute of Pharmacology and Morphophysiology, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile (R.A.B.)
| | - Rafael A. Burgos
- Laboratory of Inflammation Pharmacology and Immunometabolism, Institute of Pharmacology and Morphophysiology, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile (R.A.B.)
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Zeng M, Hodges JK, Pokala A, Khalafi M, Sasaki GY, Pierson J, Cao S, Brock G, Yu Z, Zhu J, Vodovotz Y, Bruno RS. A green tea extract confection decreases circulating endotoxin and fasting glucose by improving gut barrier function but without affecting systemic inflammation: A double-blind, placebo-controlled randomized trial in healthy adults and adults with metabolic syndrome. Nutr Res 2024; 124:94-110. [PMID: 38430822 DOI: 10.1016/j.nutres.2024.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 01/11/2024] [Accepted: 02/01/2024] [Indexed: 03/05/2024]
Abstract
Anti-inflammatory activities of catechin-rich green tea extract (GTE) in obese rodents protect against metabolic endotoxemia by decreasing intestinal permeability and absorption of gut-derived endotoxin. However, translation to human health has not been established. We hypothesized that GTE would reduce endotoxemia by decreasing gut permeability and intestinal and systemic inflammation in persons with metabolic syndrome (MetS) compared with healthy persons. A randomized, double-blind, placebo-controlled, crossover trial in healthy adults (n = 19, 34 ± 2 years) and adults with MetS (n = 21, 40 ± 3 years) examined 4-week administration of a decaffeinated GTE confection (890 mg/d total catechins) on serum endotoxin, intestinal permeability, gut and systemic inflammation, and cardiometabolic parameters. Compared with the placebo, the GTE confection decreased serum endotoxin (P = .023) in both healthy persons and those with MetS, while increasing concentrations of circulating catechins (P < .0001) and γ-valerolactones (P = .0001). Fecal calprotectin (P = .029) and myeloperoxidase (P = .048) concentrations were decreased by GTE regardless of health status. Following the ingestion of gut permeability probes, urinary lactose/mannitol (P = .043) but not sucralose/erythritol (P > .05) was decreased by GTE regardless of health status. No between-treatment differences (P > .05) were observed for plasma aminotransferases, blood pressure, plasma lipids, or body mass nor were plasma tumor necrosis factor-α, interleukin-6, or the ratio of lipopolysaccharide-binding protein/soluble cluster of differentiation-14 affected. However, fasting glucose in both study groups was decreased (P = .029) by the GTE confection compared with within-treatment arm baseline concentrations. These findings demonstrate that catechin-rich GTE is effective to decrease circulating endotoxin and improve glycemic control in healthy adults and those with MetS, likely by reducing gut inflammation and small intestinal permeability but without affecting systemic inflammation.
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Affiliation(s)
- Min Zeng
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
| | - Joanna K Hodges
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA; Department of Nutritional Sciences, The Pennsylvania State University, State College, PA, 16801, USA
| | - Avinash Pokala
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
| | - Mona Khalafi
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
| | - Geoffrey Y Sasaki
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
| | - Jillian Pierson
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
| | - Sisi Cao
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
| | - Guy Brock
- Department of Biomedical Informatics, The Ohio State University, Columbus, OH, 43210, USA
| | - Zhongtang Yu
- Department of Animal Sciences, The Ohio State University, Columbus, OH, 43210, USA
| | - Jiangjiang Zhu
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
| | - Yael Vodovotz
- Department of Food Science and Technology, The Ohio State University, Columbus, OH, 43210, USA
| | - Richard S Bruno
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA.
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Zhao J, Hussain SA, Maddu N. Combined administration of gallic acid and glibenclamide mitigate systemic complication and histological changes in the cornea of diabetic rats induced with streptozotocin. Acta Cir Bras 2024; 39:e390124. [PMID: 38324798 PMCID: PMC10852537 DOI: 10.1590/acb390124] [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: 07/13/2023] [Accepted: 10/16/2023] [Indexed: 02/09/2024] Open
Abstract
PURPOSE To determine the effect of gallic acid or its combination with glibenclamide on some biochemical markers and histology of the cornea of streptozotocin (STZ) induced diabetic rats. METHODS Following induction of diabetes, 24 male albino rats were divided into four groups of six rats each. Groups 1 and 2 (control and diabetic) received rat pellets and distilled water; group 3 (gallic acid) received rat pellets and gallic acid (10 mg/kg, orally) dissolved in the distilled water; and group 4 (gallic acid + glibenclamide) received rat pellets, gallic acid (10 mg/kg, orally), and glibenclamide (5 mg/kg, orally) dissolved in the distilled water. The treatments were administered for three months after which the rats were sacrificed after an overnight fast. Blood and sera were collected for the determination of biochemical parameters, while their eyes were excised for histology. RESULTS STZ administration to the rats induced insulin resistance, hyperglycemia, microprotenuria, loss of weight, oxidative stress, inflammation, and alteration of their cornea histology, which was abolished following supplementation with gallic acid or its combination with glibenclamide. CONCLUSIONS The study showed the potentials of gallic acid and glibenclamide in mitigating systemic complication and histological changes in the cornea of diabetic rats induced with STZ.
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Affiliation(s)
- Jing Zhao
- Sanmenxia Central Hospital – Department of Ophthalmology – Sanmenxia – China
| | - Shaik Althaf Hussain
- King Saud University – College of Science – Department of Zoology – Riyadh – Saudi Arabia
| | - Narendra Maddu
- Sri Krishnadevaraya University – Department of Biochemistry – Anantapur – India
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Su Y, Qiu P, Cheng L, Zhang L, Peng W, Meng X. Catechin Protects against Lipopolysaccharide-induced Depressive-like Behaviour in Mice by Regulating Neuronal and Inflammatory Genes. Curr Gene Ther 2024; 24:292-306. [PMID: 38783529 DOI: 10.2174/0115665232261045231215054305] [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: 05/29/2023] [Revised: 11/09/2023] [Accepted: 11/15/2023] [Indexed: 05/25/2024]
Abstract
BACKGROUND Many studies have suggested that tea has antidepressant effects; however, the underlying mechanism is not fully studied. As the main anti-inflammatory polyphenol in tea, catechin may contribute to the protective role of tea against depression. OBJECTIVE The objective of this study is to prove that catechin can protect against lipopolysaccharide (LPS)-induced depressive-like behaviours in mice, and then explore the underlying molecular mechanisms. METHODS Thirty-one C57BL/6J mice were categorized into the normal saline (NS) group, LPS group, catechin group, and amitriptyline group according to their treatments. Elevated Plus Maze (EPM), Tail Suspension Test (TST), and Open Field Test (OFT) were employed to assess depressive- like behaviours in mice. RNA sequencing (RNA-seq) and subsequent Bioinformatics analyses, such as differential gene analysis and functional enrichment, were performed on the four mouse groups. RESULTS In TST, the mice in the LPS group exhibited significantly longer immobility time than those in the other three groups, while the immobility times for the other three groups were not significantly different. Similarly in EPM, LPS-treated mice exhibited a significantly lower percentage in the time/path of entering open arms than the mice in the other three groups, while the percentages of the mice in the other three groups were not significantly different. In OFT, LPS-treated mice exhibited significantly lower percentages in the time/path of entering the centre area than those in the other three groups. The results suggested that the LPS-induced depression models were established successfully and catechin can reverse (LPS)-induced depressive-like behaviours in mice. Finally, RNA-seq analyses revealed 57 differential expressed genes (DEGs) between LPS and NS with 19 up-regulated and 38 down-regulated. Among them, 13 genes were overlapped with the DEGs between LPS and cetechin (in opposite directions), with an overlapping p-value < 0.001. The 13 genes included Rnu7, Lcn2, C4b, Saa3, Pglyrp1, Gpx3, Lyz2, S100a8, S100a9, Tmem254b, Gm14288, Hbb-bt, and Tmem254c, which might play key roles in the protection of catechin against LPS-induced depressive-like behaviours in mice. The 13 genes were significantly enriched in defense response and inflammatory response, indicating that catechin might work through counteracting changes in the immune system induced by LPS. CONCLUSION Catechin can protect mice from LPS-induced depressive-like behaviours through affecting inflammatory pathways and neuron-associated gene ontologies.
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Affiliation(s)
- Yanfang Su
- Department of Neurobiology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Ping Qiu
- Department of Neurobiology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Li Cheng
- Department of Neurobiology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Lijing Zhang
- Department of Neurobiology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Wenpeng Peng
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xianfang Meng
- Department of Neurobiology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
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Pelczyńska M, Moszak M, Wesołek A, Bogdański P. The Preventive Mechanisms of Bioactive Food Compounds against Obesity-Induced Inflammation. Antioxidants (Basel) 2023; 12:1232. [PMID: 37371961 DOI: 10.3390/antiox12061232] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 06/03/2023] [Accepted: 06/05/2023] [Indexed: 06/29/2023] Open
Abstract
Dietary patterns are promising strategies for preventing and treating obesity and its coexisting inflammatory processes. Bioactive food compounds have received considerable attention due to their actions against obesity-induced inflammation, with limited harmful side effects. They are perceived as food ingredients or dietary supplements other than those necessary to meet basic human nutritional needs and are responsible for positive changes in the state of health. These include polyphenols, unsaturated fatty acids, and probiotics. Although the exact mechanisms of bioactive food compounds' action are still poorly understood, studies have indicated that they involve the modulation of the secretion of proinflammatory cytokines, adipokines, and hormones; regulate gene expression in adipose tissue; and modify the signaling pathways responsible for the inflammatory response. Targeting the consumption and/or supplementation of foods with anti-inflammatory potential may represent a new approach to obesity-induced inflammation treatment. Nevertheless, more studies are needed to evaluate strategies for bioactive food compound intake, especially times and doses. Moreover, worldwide education about the advantages of bioactive food compound consumption is warranted to limit the consequences of unhealthy dietary patterns. This work presents a review and synthesis of recent data on the preventive mechanisms of bioactive food compounds in the context of obesity-induced inflammation.
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Affiliation(s)
- Marta Pelczyńska
- Chair and Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 84 Szamarzewskiego Street, 60-569 Poznań, Poland
| | - Małgorzata Moszak
- Chair and Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 84 Szamarzewskiego Street, 60-569 Poznań, Poland
| | - Agnieszka Wesołek
- Chair and Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 84 Szamarzewskiego Street, 60-569 Poznań, Poland
- Doctoral School, Poznan University of Medical Sciences, 10 Fredry Street, 61-701 Poznań, Poland
| | - Paweł Bogdański
- Chair and Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 84 Szamarzewskiego Street, 60-569 Poznań, Poland
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Yang TY, Yu MH, Wu YL, Hong CC, Chen CS, Chan KC, Wang CJ. Mulberry Leaf ( Morus alba L.) Extracts and Its Chlorogenic Acid Isomer Component Improve Glucolipotoxicity-Induced Hepatic Lipid Accumulation via Downregulating miR-34a and Decreased Inflammation. Nutrients 2022; 14:nu14224808. [PMID: 36432495 PMCID: PMC9695749 DOI: 10.3390/nu14224808] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 11/11/2022] [Accepted: 11/11/2022] [Indexed: 11/16/2022] Open
Abstract
Mulberry leaf (Morus alba L.) is used as a traditional medicine and potential health food to treat various metabolic diseases, such as hypertension, diabetes, and hyperlipidemia. However, we sought the mechanisms by which functional components of mulberry leaves mediate diabetic steatohepatitis. We applied an in vitro model of HepG2 cells induced by glucolipotoxicity and evaluated the effects of MLE and its major components nCGA, Crp, and CGA. The results showed that MLE and nCGA reduced liver fat accumulation by inhibiting SREBP-1/FASN, SREBP-2/HMG-CoAR, and activating PPARα/CPT-1. Additionally, MLE and nCGA decreased inflammatory responses associated with NF-κB, TNF-α, and IL-6 to alleviate steatohepatitis. Furthermore, we showed that MLE and nCGA exerted anti-glucolipotoxicity effects by downregulating miR-34a, thus activating SIRT1/AMPK signaling, and subsequently suppressing hepatic lipid accumulation.
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Affiliation(s)
- Tsung-Yuan Yang
- Department of Internal Medicine, Chung-Shan Medical University Hospital, No. 110, Section 1, Jianguo N. Road, Taichung 402, Taiwan
- School of Medicine, Institute of Medicine, Chung-Shan Medical University, No. 110, Section 1, Jianguo N. Road, Taichung 402, Taiwan
| | - Meng-Hsun Yu
- Department of Health Industry Technology Management, Chung Shan Medical University, No. 110, Section 1, Jianguo N. Road, Taichung 402, Taiwan
- Department of Nutrition, Chung Shan Medical University, No. 110, Section 1, Jianguo N. Road, Taichung 402, Taiwan
| | - Yi-Liang Wu
- Division of Cardiovascular Surgery, Surgical Department, Chung Shan Medical University Hospital, No. 110, Section 1, Jianguo N. Road, Taichung 402, Taiwan
- Department of Surgery, School of Medicine, Chung-Shan Medical University, No. 110, Section 1, Jianguo N. Road, Taichung 402, Taiwan
| | - Ching-Chun Hong
- Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan
| | - Chin-Shuh Chen
- Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan
| | - Kuei-Chuan Chan
- Department of Internal Medicine, Chung-Shan Medical University Hospital, No. 110, Section 1, Jianguo N. Road, Taichung 402, Taiwan
- School of Medicine, Institute of Medicine, Chung-Shan Medical University, No. 110, Section 1, Jianguo N. Road, Taichung 402, Taiwan
- Correspondence: (K.-C.C.); (C.-J.W.); Tel.: +886-4-247-30022 (ext. 34704) (K.-C.C. & C.-J.W.)
| | - Chau-Jong Wang
- Department of Health Industry Technology Management, Chung Shan Medical University, No. 110, Section 1, Jianguo N. Road, Taichung 402, Taiwan
- Department of Medical Research, Chung Shan Medical University Hospital, No. 110, Section 1, Jianguo N. Road, Taichung 402, Taiwan
- Correspondence: (K.-C.C.); (C.-J.W.); Tel.: +886-4-247-30022 (ext. 34704) (K.-C.C. & C.-J.W.)
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Sun X, Dey P, Bruno RS, Zhu J. EGCG and catechin relative to green tea extract differentially modulate the gut microbial metabolome and liver metabolome to prevent obesity in mice fed a high-fat diet. J Nutr Biochem 2022; 109:109094. [PMID: 35777589 PMCID: PMC10332503 DOI: 10.1016/j.jnutbio.2022.109094] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 05/12/2022] [Accepted: 06/13/2022] [Indexed: 11/21/2022]
Abstract
Green tea extract (GTE) alleviates obesity, in part, by modulating gut microbial composition and metabolism. However, direct evidence regarding the catechin-specific bioactivities that are responsible for these benefits remain unclear. The present study therefore investigated dietary supplementation of GTE, epigallocatechin gallate (EGCG), or (+)-catechin (CAT) in male C57BL6/J mice that were fed a high-fat (HF) diet to establish the independent contributions of EGCG and CAT relative to GTE to restore microbial and host metabolism. We hypothesized that EGCG would regulate the gut microbial metabolome and host liver metabolome more similar to GTE than CAT to explain their previously observed differential effects on cardiometabolic health. To test this, we assessed metabolic and phenolic shifts in liver and fecal samples during dietary HF-induced obesity. Ten fecal metabolites and ten liver metabolites (VIP > 2) primarily contributed to the differences in the metabolome among different interventions. In fecal samples, nine metabolic pathways (e.g., tricarboxcylic acid cycle and tyrosine metabolism) were differentially altered between the GTE and CAT interventions, whereas three pathways differed between GTE and EGCG interventions, suggesting differential benefits of GTE and its distinctive bioactive components on gut microbial metabolism. Likewise, hepatic glycolysis / gluconeogenesis metabolic pathways were significantly altered between GTE and EGCG interventions, while only hepatic tyrosine metabolism was altered between CAT and GTE interventions. Thus, our findings support that purified catechins relative to GTE uniquely contribute to regulating host and microbial metabolic pathways such as central energy metabolism to protect against metabolic dysfunction leading to obesity.
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Affiliation(s)
- Xiaowei Sun
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Priyankar Dey
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH, USA; Department of Biotechnology, Thapar Institute of Engineering & Technology, Punjab, India
| | - Richard S Bruno
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH, USA.
| | - Jiangjiang Zhu
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
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Zhang S, Xu M, Sun X, Shi H, Zhu J. Green tea extract alters gut microbiota and their metabolism of adults with metabolic syndrome in a host-free human colonic model. Food Res Int 2022; 160:111762. [PMID: 36076430 PMCID: PMC10324538 DOI: 10.1016/j.foodres.2022.111762] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Revised: 07/26/2022] [Accepted: 07/28/2022] [Indexed: 11/04/2022]
Abstract
BACKGROUND Metabolic syndrome (MetS) is a common metatoblic disorder that leads to various adverse health outcomes such as diabetes and cardiovascular diseases (CVDs). Recent studies suggested that MetS-associated gut dysbiosis could exacerbate MetS related diseases. Green tea, a popular beverage rich in polyphenols, has showed antioxidant and anti-inflammatory effects in treating MetS through gut modulation. OBJECTIVES This study aimed to understand the impact of green tea extract (GTE) on the composition and metabolism of gut microbiota from people with MetS. METHODS We utilized an in-vitro human colonic model (HCM) to specifically investigate the host-free interactions between GTE and gut microbiota of MetS adults. Fresh fecal samples donated by three adults with MetS were used as gut microbe inoculum in our HCM system. 16S ribosomal RNA sequencing and liquid-chromatography mass spectrometry (LC/MS) combined with QIIME 2, Compound Discoverer 3.1 and MetaboAnalyst 4.0 based data analyses were performed to show the regulating effects of GTE treatment on gut microbial composition and their metabolism. RESULTS Our data suggested that GTE treatment in HCM system modified composition of MetS gut microbiota at genus level and led to significant microbiota metabolic profile change. Bioinformatics analysis showed relative abundance of Escherichia and Klebsiella was commonly increased while Bacteroides, Citrobacter, and Clostridium were significantly reduced. All free fatty acids detected were significantly increased in different colon sections. Lipopolysaccharide biosynthesis, methane metabolism, pentose phosphate pathway, purine metabolism, and tyrosine metabolism were regulated by GTE in MetS gut microbiota. In addition, we identified significant associations between altered microbes and microbial metabolites. CONCLUSIONS Overall, our study revealed the impact of GTE treatment on gut microbiota composition and metabolism changes in MetS microbiota in vitro, which may provide information for further mechanistic investigation of GTE in modulating gut dysbiosis in MetS.
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Affiliation(s)
- Shiqi Zhang
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA
| | - Mengyang Xu
- Department of Biology, Miami University, Oxford, OH 45056, USA
| | - Xiaowei Sun
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA
| | - Haifei Shi
- Department of Biology, Miami University, Oxford, OH 45056, USA
| | - Jiangjiang Zhu
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA; James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
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10
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Liu C, Boeren S, Miro Estruch I, Rietjens IMCM. The Gut Microbial Metabolite Pyrogallol Is a More Potent Inducer of Nrf2-Associated Gene Expression Than Its Parent Compound Green Tea (-)-Epigallocatechin Gallate. Nutrients 2022; 14:nu14163392. [PMID: 36014899 PMCID: PMC9414524 DOI: 10.3390/nu14163392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 08/16/2022] [Accepted: 08/17/2022] [Indexed: 11/16/2022] Open
Abstract
(-)-Epigallocatechin gallate (EGCG) has been associated with multiple beneficial effects. However, EGCG is known to be degraded by the gut microbiota. The present study investigated the hypothesis that microbial metabolism would create major catechol-moiety-containing microbial metabolites with different ability from EGCG to induce nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated gene expression. A reporter gene bioassay, label-free quantitative proteomics and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) were combined to investigate the regulation of Nrf2-related gene expression after exposure of U2OS reporter gene or Hepa1c1c7 cells in vitro to EGCG or to its major microbial catechol-moiety-containing metabolites: (-)-epigallocatechin (EGC), gallic acid (GA) and pyrogallol (PG). Results show that PG was a more potent inducer of Nrf2-mediated gene expression than EGCG, with a 5% benchmark dose (BMD5) of 0.35 µM as compared to 2.45 µM for EGCG in the reporter gene assay. EGC and GA were unable to induce Nrf2-mediated gene expression up to the highest concentration tested (75 µM). Bioinformatical analysis of the proteomics data indicated that Nrf2 induction by PG relates to glutathione metabolism, drug and/or xenobiotics metabolism and the pentose phosphate pathway. Taken together, our findings demonstrate that the microbial metabolite PG is a more potent inducer of Nrf2-associated gene expression than its parent compound EGCG.
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Affiliation(s)
- Chen Liu
- Tea Refining and Innovation Key Laboratory of Sichuan Province, College of Horticulture, Sichuan Agricultural University, Chengdu 611130, China
- Division of Toxicology, Wageningen University and Research, 6708 WE Wageningen, The Netherlands
- Correspondence:
| | - Sjef Boeren
- Laboratory of Biochemistry, Wageningen University and Research, 6708 WE Wageningen, The Netherlands
| | - Ignacio Miro Estruch
- Division of Toxicology, Wageningen University and Research, 6708 WE Wageningen, The Netherlands
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11
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Eleazu C, Suleiman JB, Othman ZA, Zakaria Z, Nna VU, Hussain NHN, Mohamed M. Bee bread attenuates high fat diet induced renal pathology in obese rats via modulation of oxidative stress, downregulation of NF-kB mediated inflammation and Bax signalling. Arch Physiol Biochem 2022; 128:1088-1104. [PMID: 32319823 DOI: 10.1080/13813455.2020.1752258] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 02/21/2020] [Accepted: 03/31/2020] [Indexed: 02/07/2023]
Abstract
CONTEXT Global prevalence of obesity is increasing. OBJECTIVE To study the effect of bee bread (BB) on serum renal function parameters, oxidative stress, inflammatory and B-cell associated protein X (Bax) in the kidneys of high fat diet (HFD) obese rats. METHODS Thirty-six male Sprague Dawley rats were used. Control: received rat diet and water (1 mL/kg); HFD group: received HFD and water (1 mL/kg): bee bread (BB) preventive or orlistat preventive: received HFD and BB (0.5 g/kg) or HFD and orlistat (10 mg/kg); BB or orlistat treatment: received BB (0.5 g/kg) or orlistat (10 mg/kg). RESULTS HFD group had increased body weight, Body Mass Index, Lee Obesity Indices, kidney weights, malondialdehyde, inflammatory markers, Bax; decreased glutathione peroxidase, glutathione-S-transferase, superoxide dismutase, total antioxidant activity, no differences (p > .05) in food intakes, serum creatinine, sodium, potassium, chloride, catalase compared to control. CONCLUSION BB modulated most of these parameters, as corroborated by histology.
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Affiliation(s)
- Chinedum Eleazu
- Department of Chemistry, Biochemistry and Molecular Biology, Alex Ekwueme Federal University, Ndufu-Alike, Ebonyi State, Nigeria
- Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - Joseph Bagi Suleiman
- Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
- Department of Science Laboratory Technology, Akanu Ibiam Federal Polytechnic, Unwana, Ebonyi State, Nigeria
| | - Zaidatul Akmal Othman
- Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
- Faculty of Medicine, Universiti Sultan Zainal Abidin, Kuala Terengganu, Terengganu, Malaysia
| | - Zaida Zakaria
- Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - Victor Udo Nna
- Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
- Department of Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, University of Calabar, Calabar, Cross River State, Nigeria
| | - Nik Hazlina Nik Hussain
- Women's Health Development Unit, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - Mahaneem Mohamed
- Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
- Unit of Integrative Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
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12
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Celecoxib-mediated attenuation of non-alcoholic steatohepatitis is potentially relevant to redistributing the expression of adiponectin receptors in rats. Heliyon 2022; 8:e09872. [PMID: 35832345 PMCID: PMC9272346 DOI: 10.1016/j.heliyon.2022.e09872] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 04/20/2022] [Accepted: 06/30/2022] [Indexed: 11/23/2022] Open
Abstract
Pharmacological inhibition of cyclooxygenase-2 (COX-2) activity ameliorated the severity of non-alcoholic steatohepatitis (NASH) rats. It is not completely understood that the role of COX-2 inhibitor celecoxib on adiponectin receptors (Adipo-R1/R2) expression in different tissues in NASH rats. Sprague-Dawley male NASH rats induced by a high-fat diet (HFD) were administrated with or without celecoxib for 8 weeks. Biochemical parameters of liver function, glucose, and lipid metabolism, and the levels of adiponectin, tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2) in the serum or liver were collected according to the standard protocols. The mRNA and protein levels of Adipo-R1, Adipo-R2, and COX-2 in the liver, muscle, and visceral fat were performed by quantitative real-time polymerase chain reaction (q-PCR) and Western blot analysis, respectively. The results showed that celecoxib ameliorated the various clinical indicators and pathological characteristics in the NASH rats, including body weight, liver function, liver index, and redox activities in serum and hepatic samples. The serum concentrations of adiponectin and TNF-α and PGE2 were negatively correlated. As expected, these ameliorative effects of celecoxib were associated with the gene and protein levels up-regulation of Adipo-R1, Adipo-R2 in the liver and visceral fat tissues, and seeming to be compensatory down-regulation expression in muscle tissues (P <0.05). Additionally, COX-2 protein expression was negatively correlated with serum adiponectin levels, protein expression of adiponectin receptors from the liver and visceral fat, conversely, positively correlated with those from the muscle. Our current study demonstrate that celecoxib might effectively alleviate NASH rats in a unique manner closely relevant to redistributing the expression of adiponectin receptors in the liver, visceral fat, and muscle. However, the precise molecular mechanism needs further study.
NASH is a watershed in the progression of NAFLD. Finding a therapy for NASH is in urgent need. Pharmacological inhibition of COX-2 activity ameliorated the severity of NASH. Low-dose celecoxib, a COX-2 inhibitor, can improve NASH by redistributing the expression of adiponectin receptors.
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13
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Zhou DD, Mao QQ, Li BY, Saimaiti A, Huang SY, Xiong RG, Shang A, Luo M, Li HY, Gan RY, Li HB, Li S. Effects of Different Green Teas on Obesity and Non-Alcoholic Fatty Liver Disease Induced by a High-Fat Diet in Mice. Front Nutr 2022; 9:929210. [PMID: 35811941 PMCID: PMC9263825 DOI: 10.3389/fnut.2022.929210] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 05/17/2022] [Indexed: 12/11/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) and obesity are serious public health problems. Green tea is widely consumed in the world and different green teas could possess different bioactivities. In this study, the effects of 10 selected green teas on obesity and NAFLD were evaluated and compared. The mice fed with a high-fat diet were intervened with green tea extract (200 mg/kg body weight) for 15 weeks. Most of these teas were first evaluated for their effects on obesity and NAFLD. The results showed that Selenium-Enriched Chaoqing Green Tea and Jieyang Chaoqing Tea showed the most prominent inhibition of obesity and body weight gains of mice in these two tea intervention groups and model groups were 5.3, 5.5, and 13.7 g, respectively. In addition, Jieyang Chaoqing Tea, Taiping Houkui Tea, and Selenium-Enriched Chaoqing Green Tea exerted the most notable effect on NAFLD, which was attributed to decreasing body weight, and lipid content and ameliorating oxidative stress. Furthermore, 13 phytochemicals were determined in these teas by high-performance liquid chromatography and the correlation analysis found that epigallocatechin gallate, gallocatechin, and epigallocatechin might contribute to the decrease of hepatic weight, while epicatechin might reduce oxidative stress. In general, several green teas could prevent the development of obesity and NAFLD and could be developed into functional foods. This study was also helpful for the public to select appropriate tea to prevent obesity and NAFLD.
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Affiliation(s)
- Dan-Dan Zhou
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Qian-Qian Mao
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Bang-Yan Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Adila Saimaiti
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Si-Yu Huang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Ruo-Gu Xiong
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Ao Shang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Min Luo
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Hang-Yu Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Ren-You Gan
- Research Center for Plants and Human Health, Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu, China
| | - Hua-Bin Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Sha Li
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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14
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Çelik Samancı T, Gökçimen A, Kuloğlu T, Boyacıoğlu M, Kuyucu Y, Polat S. Biochemical and Histopathological Investigation of Liver Tissues on High Fat Diet Fed Rats. MEANDROS MEDICAL AND DENTAL JOURNAL 2022. [DOI: 10.4274/meandros.galenos.2021.32932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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15
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Mehta R, Bhandari R, Kuhad A. Effects of catechin on a rodent model of autism spectrum disorder: implications for the role of nitric oxide in neuroinflammatory pathway. Psychopharmacology (Berl) 2021; 238:3249-3271. [PMID: 34448020 DOI: 10.1007/s00213-021-05941-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 07/20/2021] [Indexed: 11/27/2022]
Abstract
AIM The present research work aims at deciphering the involvement of nitric oxide pathway and its modulation by ( ±)catechin hydrate in experimental paradigm of autism spectrum disorders (ASD). METHOD An intracerebroventricular infusion of 4 μl of 1 M propanoic acid was given in the anterior region of the lateral ventricle to induce autism-like phenotype in male rats. Oral administration of ( ±)catechin hydrate (25, 50, and 100 mg/kg) was initiated from the 3rd day lasting till the 28th day. L-NAME (50 mg/kg) and L-arginine (800 mg/kg) were also given individually as well as in combination to explore the ability of ( ±)catechin hydrate to act via nitric oxide pathway. Behavior test for sociability, stereotypy, anxiety, depression, and novelty, repetitive, and perseverative behavior was carried out between the 14th and 28th day. On the 29th day, animals were sacrificed, and levels of mitochondrial complexes and oxidative stress parameters were evaluated. We also estimated the levels of neuroinflammatory and apoptotic markers such as TNF-α, IL-6, NF-κB, IFN-γ, HSP-70, and caspase-3. To evaluate the involvement of nitric oxide pathway, the levels of iNOS and homocysteine were estimated. RESULTS Treatment with ( ±)catechin hydrate significantly ameliorated behavioral, biochemical, neurological, and molecular deficits. Hence, ( ±)catechin hydrate has potential to be used as neurotherapeutic agent in ASD targeting nitric oxide pathway-mediated oxidative and nitrosative stress responsible for behavioral, biochemical, and molecular alterations via modulating nitric oxide pathway. CONCLUSION The evaluation of the levels of iNOS and homocysteine conclusively establishes the role of nitric oxide pathway in causing behavioral, biochemical, and molecular deficits and the beneficial effect of ( ±)catechin hydrate in restoring these alterations.
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Affiliation(s)
- Rishab Mehta
- Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh, 160 014, India
| | - Ranjana Bhandari
- Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh, 160 014, India.
| | - Anurag Kuhad
- Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh, 160 014, India.
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16
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Chung MY, Kim HJ, Choi HK, Park JH, Hwang JT. Black Mulberry Extract Elicits Hepatoprotective Effects in Nonalcoholic Fatty Liver Disease Models by Inhibition of Histone Acetylation. J Med Food 2021; 24:978-986. [PMID: 34524028 DOI: 10.1089/jmf.2021.k.0048] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Epigenetic regulation by histone acetyltransferase (HAT) is associated with various biological processes and the progression of diseases, including nonalcoholic fatty liver disease (NAFLD). The objective of this study was to investigate whether the hypolipidemic properties of black mulberry (Morus atropurpurea Roxb.) fruit extract (BME) contribute toward protection against NAFLD by HAT inhibition. HepG2 cells were treated with oleic and palmitic acids to induce lipid accumulation, which was significantly attenuated by the treatment with BME at 50 and 100 μg/mL. BME also markedly reduced the expression of proteins associated with lipogenesis, which was attributed to the BME-mediated downregulation of lipogenic genes in HepG2 cells. BME significantly inhibited in vitro total HAT and p300 activities. In addition, BME suppressed total acetylated lysine as well as specific histone acetylation of proteins H3K14 and H3K27 in HepG2 cells. Mice were then fed with either a chow diet or western diet (WD), with or without BME (1%, w/w) supplementation, for 12 weeks to confirm hypolipidemic activity of BME. BME attenuated serum nonesterified fatty acids and low-density lipoprotein (LDL) cholesterol levels, which was likely associated with the downregulation of hepatic lipogenic gene expression in WD-fed obese mice. Taken together, the hypolipidemic activity of BME was observed in HepG2 cells treated with fatty acids as well as in livers of obese mice, and the hepatoprotection of BME is likely associated with the inhibition of acetylation. Further investigation is warranted to determine whether BME can be developed into an efficacious dietary intervention to attenuate the progression of NAFLD by epigenetic regulation in clinical settings.
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Affiliation(s)
- Min-Yu Chung
- Research Group of Healthcare, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Korea
| | - Hyo-Jin Kim
- Research Group of Healthcare, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Korea.,Department of Food Biotechnology, Korea University of Science and Technology, Daejeon, Korea
| | - Hyo-Kyoung Choi
- Research Group of Healthcare, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Korea
| | - Jae Ho Park
- Research Group of Healthcare, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Korea
| | - Jin-Taek Hwang
- Research Group of Healthcare, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Korea.,Department of Food Biotechnology, Korea University of Science and Technology, Daejeon, Korea
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17
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Bhattacharya S, Paul SMN. Efficacy of phytochemicals as immunomodulators in managing COVID-19: a comprehensive view. Virusdisease 2021; 32:435-445. [PMID: 34189187 PMCID: PMC8224255 DOI: 10.1007/s13337-021-00706-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 06/11/2021] [Indexed: 12/15/2022] Open
Abstract
Throughout history, disease outbreaks have worked havoc upon humanity, sometimes reorienting the history and at times, signaling the end of entire civilizations and the modern pandemic that the world is dealing with, is COVID-19 or SARS-CoV-2. A healthy immunity could be an ideal gear for resisting COVID-19 for neither medicines nor vaccines have been ascertained till date. In view of the present scenario, there is a demanding necessity to analyze innovative and valid techniques for forestalling and cure of COVID-19 by re-evaluating the structure of the natural compounds for drug designing. The Ayurveda has come forward by prescribing a lot of medicinal herbs for combating this dreaded disease. We have searched from sources in Pubmed and Google Scholar and found 1509 items. The search criteria were limited to the effect of phytochemicals in certain immunomodulatory aspects of viral infection. The original research papers related to the works on phytochemicals in the down regulation of NF-kB, activation of NK and CD8+ cells, inhibition of inflammatory cytokine release and ROS scavenging were included in our study. Here, we try to focus on the immunoregulatory cells which have a vital aspect in COVID-19 and highlight the potential effects of the restorative use of phytochemicals as drugs or dietary supplements. Supplementary Information The online version contains supplementary material available at 10.1007/s13337-021-00706-2.
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Affiliation(s)
- Sonali Bhattacharya
- Department of Zoology, Rishi Bankim Chandra College, Naihati, West Bengal 743165 India
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18
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Tang G, Xu Y, Zhang C, Wang N, Li H, Feng Y. Green Tea and Epigallocatechin Gallate (EGCG) for the Management of Nonalcoholic Fatty Liver Diseases (NAFLD): Insights into the Role of Oxidative Stress and Antioxidant Mechanism. Antioxidants (Basel) 2021; 10:1076. [PMID: 34356308 PMCID: PMC8301033 DOI: 10.3390/antiox10071076] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 06/27/2021] [Accepted: 07/01/2021] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver diseases (NAFLD) represent a set of liver disorders progressing from steatosis to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma, which induce huge burden to human health. Many pathophysiological factors are considered to influence NAFLD in a parallel pattern, involving insulin resistance, oxidative stress, lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, inflammatory cascades, fibrogenic reaction, etc. However, the underlying mechanisms, including those that induce NAFLD development, have not been fully understood. Specifically, oxidative stress, mainly mediated by excessive accumulation of reactive oxygen species, has participated in the multiple NAFLD-related signaling by serving as an accelerator. Ameliorating oxidative stress and maintaining redox homeostasis may be a promising approach for the management of NAFLD. Green tea is one of the most important dietary resources of natural antioxidants, above which epigallocatechin gallate (EGCG) notably contributes to its antioxidative action. Accumulative evidence from randomized clinical trials, systematic reviews, and meta-analysis has revealed the beneficial functions of green tea and EGCG in preventing and managing NAFLD, with acceptable safety in the patients. Abundant animal and cellular studies have demonstrated that green tea and EGCG may protect against NAFLD initiation and development by alleviating oxidative stress and the related metabolism dysfunction, inflammation, fibrosis, and tumorigenesis. The targeted signaling pathways may include, but are not limited to, NRF2, AMPK, SIRT1, NF-κB, TLR4/MYD88, TGF-β/SMAD, and PI3K/Akt/FoxO1, etc. In this review, we thoroughly discuss the oxidative stress-related mechanisms involved in NAFLD development, as well as summarize the protective effects and underlying mechanisms of green tea and EGCG against NAFLD.
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Affiliation(s)
- Guoyi Tang
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China; (G.T.); (Y.X.); (C.Z.); (N.W.)
| | - Yu Xu
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China; (G.T.); (Y.X.); (C.Z.); (N.W.)
| | - Cheng Zhang
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China; (G.T.); (Y.X.); (C.Z.); (N.W.)
| | - Ning Wang
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China; (G.T.); (Y.X.); (C.Z.); (N.W.)
| | - Huabin Li
- School of Public Health, Sun Yat-sen University, Guangzhou 510080, China;
| | - Yibin Feng
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China; (G.T.); (Y.X.); (C.Z.); (N.W.)
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Monfoulet LE, Ruskovska T, Ajdžanović V, Havlik J, Vauzour D, Bayram B, Krga I, Corral-Jara KF, Kistanova E, Abadjieva D, Massaro M, Scoditti E, Deligiannidou E, Kontogiorgis C, Arola-Arnal A, van Schothorst EM, Morand C, Milenkovic D. Molecular Determinants of the Cardiometabolic Improvements of Dietary Flavanols Identified by an Integrative Analysis of Nutrigenomic Data from a Systematic Review of Animal Studies. Mol Nutr Food Res 2021; 65:e2100227. [PMID: 34048642 DOI: 10.1002/mnfr.202100227] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 05/21/2021] [Indexed: 12/11/2022]
Abstract
SCOPE Flavanols are important polyphenols of the human diet with extensive demonstrations of their beneficial effects on cardiometabolic health. They contribute to preserve health acting on a large range of cellular processes. The underlying mechanisms of action of flavanols are not fully understood but involve a nutrigenomic regulation. METHODS AND RESULTS To further capture how the intake of dietary flavanols results in the modulation of gene expression, nutrigenomics data in response to dietary flavanols obtained from animal models of cardiometabolic diseases have been collected and submitted to a bioinformatics analysis. This systematic analysis shows that dietary flavanols modulate a large range of genes mainly involved in endocrine function, fatty acid metabolism, and inflammation. Several regulators of the gene expression have been predicted and include transcription factors, miRNAs and epigenetic factors. CONCLUSION This review highlights the complex and multilevel action of dietary flavanols contributing to their strong potential to preserve cardiometabolic health. The identification of the potential molecular mediators and of the flavanol metabolites driving the nutrigenomic response in the target organs is still a pending question which the answer will contribute to optimize the beneficial health effects of dietary bioactives.
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Affiliation(s)
| | - Tatjana Ruskovska
- Faculty of Medical Sciences, Goce Delcev University, Stip, North Macedonia
| | - Vladimir Ajdžanović
- Department of Cytology, Institute for Biological Research "Siniša Stanković,", National Institute of Republic of Serbia, University of Belgrade, 142 Despot Stefan Blvd., Belgrade, Serbia
| | - Jaroslav Havlik
- Department of Food Science, Czech University of Life Sciences Prague, Prague 6, Suchdol, Czech Republic
| | - David Vauzour
- Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK
| | - Banu Bayram
- Department of Nutrition and Dietetics, University of Health Sciences, Istanbul, Turkey
| | - Irena Krga
- Université Clermont Auvergne, INRAE, UNH, Clermont-Ferrand, F-63000, France.,Centre of Excellence in Nutrition and Metabolism Research, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | | | - Elena Kistanova
- Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, Sofia, Bulgaria
| | - Desislava Abadjieva
- Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, Sofia, Bulgaria
| | - Marika Massaro
- National Research Council (CNR) Institute of Clinical Physiology, Lecce, Italy
| | - Egeria Scoditti
- National Research Council (CNR) Institute of Clinical Physiology, Lecce, Italy
| | - Eirini Deligiannidou
- Laboratory of Hygiene and Environmental Protection, Department of Medicine, Democritus University of Thrace, Alexandroupolis, 68100, Greece
| | - Christos Kontogiorgis
- Laboratory of Hygiene and Environmental Protection, Department of Medicine, Democritus University of Thrace, Alexandroupolis, 68100, Greece
| | - Anna Arola-Arnal
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Nutrigenomics Research Group, Tarragona, 43007, Spain
| | | | - Christine Morand
- Université Clermont Auvergne, INRAE, UNH, Clermont-Ferrand, F-63000, France
| | - Dragan Milenkovic
- Université Clermont Auvergne, INRAE, UNH, Clermont-Ferrand, F-63000, France.,Department of Internal Medicine, Division of Cardiovascular Medicine, School of Medicine, University of California Davis, Davis, California, 95616, USA
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Tanaka Y, Kumazoe M, Onda H, Fujimura Y, Tachibana H. Time-dependent increase of plasma cGMP concentration followed by oral EGCG administration in mice. FOOD BIOSCI 2021. [DOI: 10.1016/j.fbio.2021.101017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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21
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Obesity and aging: Molecular mechanisms and therapeutic approaches. Ageing Res Rev 2021; 67:101268. [PMID: 33556548 DOI: 10.1016/j.arr.2021.101268] [Citation(s) in RCA: 116] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 01/19/2021] [Accepted: 02/02/2021] [Indexed: 02/08/2023]
Abstract
The epidemic of obesity is a major challenge for health policymakers due to its far-reaching effects on population health and potentially overwhelming financial burden on healthcare systems. Obesity is associated with an increased risk of developing acute and chronic diseases, including hypertension, stroke, myocardial infarction, cardiovascular disease, diabetes, and cancer. Interestingly, the metabolic dysregulation associated with obesity is similar to that observed in normal aging, and substantial evidence suggests the potential of obesity to accelerate aging. Therefore, understanding the mechanism of fat tissue dysfunction in obesity could provide insights into the processes that contribute to the metabolic dysfunction associated with the aging process. Here, we review the molecular and cellular mechanisms underlying both obesity and aging, and how obesity and aging can predispose individuals to chronic health complications. The potential of lifestyle and pharmacological interventions to counter obesity and obesity-related pathologies, as well as aging, is also addressed.
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The Cholesterol-Lowering Effect of Capsella Bursa-Pastoris Is Mediated via SREBP2 and HNF-1α-Regulated PCSK9 Inhibition in Obese Mice and HepG2 Cells. Foods 2021; 10:foods10020408. [PMID: 33673187 PMCID: PMC7918551 DOI: 10.3390/foods10020408] [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: 12/16/2020] [Revised: 02/06/2021] [Accepted: 02/09/2021] [Indexed: 12/14/2022] Open
Abstract
The objective of the present study was to investigate the mechanism by which capsella bursa-pastoris ethanol extract (CBE), containing 17.5 milligrams of icaritin per kilogram of the extract, and icaritin, mediate hypocholesterolemic activity via the low-density lipoprotein receptor (LDLR) and pro-protein convertase subtilisin/kexin type 9 (PCSK9) in obese mice and HepG2 cells. CBE significantly attenuated serum total and LDL cholesterol levels in obese mice, which was associated with significantly decreased PCSK9 gene expression. HepG2 cells were cultured using delipidated serum (DLPS), and CBE significantly reduced PCSK9 and maintained the LDLR level. CBE co-treatment with rosuvastatin attenuated statin-mediated PCSK9 expression, and further increased LDLR. The icaritin contained in CBE decreased intracellular PCSK9 and LDLR levels by suppressing transcription factors SREBP2 and HNF-1α. Icaritin also significantly suppressed the extracellular PCSK9 level, which likely contributed to post-translational stabilization of LDLR in the HepG2 cells. PCSK9 inhibition by CBE is actively attributed to icaritin, and the use of CBE and icaritin could be an alternative therapeutic approach in the treatment of hypercholesterolemia.
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Sasaki GY, Li J, Cichon MJ, Kopec RE, Bruno RS. Catechin-Rich Green Tea Extract and the Loss-of-TLR4 Signaling Differentially Alter the Hepatic Metabolome in Mice with Nonalcoholic Steatohepatitis. Mol Nutr Food Res 2021; 65:e2000998. [PMID: 33249742 DOI: 10.1002/mnfr.202000998] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 11/13/2020] [Indexed: 01/03/2023]
Abstract
SCOPE Catechin-rich green tea extract (GTE) limits inflammation in nonalcoholic steatohepatitis (NASH) consistent with a Toll-like receptor 4 (TLR4)-dependent mechanism. It is hypothesized that GTE supplementation during NASH will shift the hepatic metabolome similar to that attributed to the loss-of-TLR4 signaling. METHODS AND RESULTS Wild-type (WT) and loss-of-function TLR4-mutant (TLR4mut ) mice are fed a high-fat diet containing 0% or 2% GTE for 8 weeks prior to performing untargeted mass spectrometry-based metabolomics on liver tissue. The loss-of-TLR4 signaling and GTE shift the hepatic metabolome away from that of WT mice. However, relatively few metabolites are altered by GTE in WT mice to the same extent as the loss-of-TLR4 signaling in TLR4mut mice. GTE increases acetyl-coenzyme A precursors and spermidine to a greater extent than the loss-of-TLR4 signaling. Select metabolites associated with thiol metabolism are similarly affected by GTE and the loss-of-TLR4 signaling. Glycerophospholipid catabolites are decreased by GTE, but are unaffected in TLR4mut mice. Conversely, the loss-of-TLR4 signaling but not GTE increases several bile acid metabolites. CONCLUSION GTE limitedly alters the hepatic metabolome consistent with a TLR4-dependent mechanism. This suggests that the anti-inflammatory activities of GTE and loss-of-TLR4 signaling that regulate hepatic metabolism to abrogate NASH are likely due to distinct mechanisms.
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Affiliation(s)
- Geoffrey Y Sasaki
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
| | - Jinhui Li
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
| | - Morgan J Cichon
- Foods for Health Discovery Theme, The Ohio State University, Columbus, OH, 43210, USA
| | - Rachel E Kopec
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
- Foods for Health Discovery Theme, The Ohio State University, Columbus, OH, 43210, USA
| | - Richard S Bruno
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
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Taranu I, Hermenean A, Bulgaru C, Pistol GC, Ciceu A, Grosu IA, Marin DE. Diet containing grape seed meal by-product counteracts AFB1 toxicity in liver of pig after weaning. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2020; 203:110899. [PMID: 32678747 DOI: 10.1016/j.ecoenv.2020.110899] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 06/11/2020] [Accepted: 06/14/2020] [Indexed: 06/11/2023]
Abstract
Liver is the earliest target for AFB1 toxicity in both human and animals. In the last decade, plant derived by-products have been used in animal feed to reduce AFB1 induced toxicity. In the present study we investigated whether the presence of 8% grape seed meal by-product is able to counteract the hepatotoxic effects produced by AFB1 in liver of pig after weaning exposed to the toxin through the contaminated feed for 28 days. Twenty four weaned cross-bred TOPIGS-40 piglets with an average body weight of 9.13±0.03 were allocated to the following experimentally treatments: control diet without AFB1 (normal compound feed for weaned pigs); contaminated diet with 320 mg kg-1 AFB1; GSM diet (compound feed plus 8% grape seed meal) and AFB1+GSM diet (320 mg kg-1 AFB1 contaminated feed plus 8% grape seed meal). Pigs fed AFB1 diet had altered performance, body weight decreasing with 25.1% (b.w.: 17.17 kg for AFB1 vs 22.92 kg for control). Exposure of piglets to AFB1 contaminated diet caused liver oxidative stress as well as liver histological damage, manly characterized by inflammatory infiltrate, fibrosis and parenchyma cells vacuolation when compared to control and GSM meal group. 94.12% of the total analysed genes (34) related to inflammation and immune response was up-regulated. The addition of GSM into the AFB1 diet diminished the gene overexpression and ameliorate histological liver injuries and oxidative stress. The protective effect of GSM diet in diminishing the AFB1 harmful effect was mediated through the decreasing of gene and protein expression of MAPKs and NF-κB signalling overexpressed by AFB1 diet. The inclusion of grape seed by-products in the diet of pigs after weaning might be used as a novel nutritional intervention to reduce aflatoxin toxicity.
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Affiliation(s)
- Ionelia Taranu
- Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, Calea Bucuresti No. 1, Balotesti, Ilfov, 077015, Romania.
| | - Anca Hermenean
- Aurel Ardelean Institute of Life Sciences, Vasile Goldis Western University of Arad, Arad, Romania
| | - Cristina Bulgaru
- Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, Calea Bucuresti No. 1, Balotesti, Ilfov, 077015, Romania
| | - Gina Cecilia Pistol
- Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, Calea Bucuresti No. 1, Balotesti, Ilfov, 077015, Romania
| | - Alina Ciceu
- Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest, Romania
| | - Iulian Alexandru Grosu
- Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, Calea Bucuresti No. 1, Balotesti, Ilfov, 077015, Romania
| | - Daniela Eliza Marin
- Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, Calea Bucuresti No. 1, Balotesti, Ilfov, 077015, Romania
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Dey P, Olmstead BD, Sasaki GY, Vodovotz Y, Yu Z, Bruno RS. Epigallocatechin gallate but not catechin prevents nonalcoholic steatohepatitis in mice similar to green tea extract while differentially affecting the gut microbiota. J Nutr Biochem 2020; 84:108455. [PMID: 32688217 DOI: 10.1016/j.jnutbio.2020.108455] [Citation(s) in RCA: 63] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Revised: 05/15/2020] [Accepted: 06/14/2020] [Indexed: 02/06/2023]
Abstract
Catechin-rich green tea extract (GTE) protects against nonalcoholic steatohepatitis (NASH) by alleviating gut-derived endotoxin translocation and hepatic Toll-like receptor-4 (TLR4)-nuclear factor κB (NFκB) inflammation. We hypothesized that intact GTE would attenuate NASH-associated responses along the gut-liver axis to a greater extent than purified (-)-epigallocatechin gallate (EGCG) or (+)-catechin (CAT). Male C57BL/6J mice were fed a low-fat diet, a high-fat (HF) diet, or the HF diet with 2% GTE, 0.3% EGCG or 0.3% CAT for 8 weeks prior to assessing NASH relative to endotoxemia, hepatic and intestinal inflammation, intestinal tight junction proteins (TJPs) and gut microbial ecology. GTE prevented HF-induced obesity to a greater extent than EGCG and CAT, whereas GTE and EGCG more favorably attenuated insulin resistance. GTE, EGCG and CAT similarly attenuated serum alanine aminotransferase and serum endotoxin, but only GTE and EGCG fully alleviated HF-induced NASH. However, hepatic TLR4/NFκB inflammatory responses that were otherwise increased in HF mice were similarly attenuated by GTE, EGCG and CAT. Each treatment also similarly prevented the HF-induced loss in expression of intestinal TJPs and hypoxia inducible factor-1α and the otherwise increased levels of ileal and colonic TNFα mRNA and fecal calprotectin protein concentrations. Gut microbial diversity that was otherwise lowered in HF mice was maintained by GTE and CAT only. Further, microbial metabolic functions were more similar between GTE and CAT. Collectively, GTE catechins similarly protect against endotoxin-TLR4-NFκB inflammation in NASH, but EGCG and CAT exert differential prebiotic and antimicrobial activities suggesting that catechin-mediated shifts in microbiota composition are not entirely responsible for their benefits along the gut-liver axis.
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Affiliation(s)
- Priyankar Dey
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA; Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, Punjab, India
| | - Bryan D Olmstead
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA
| | - Geoffrey Y Sasaki
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA
| | - Yael Vodovotz
- Department of Food Science and Technology, The Ohio State University, Columbus, OH, USA
| | - Zhongtang Yu
- Department of Animal Sciences, The Ohio State University, Columbus, OH, USA
| | - Richard S Bruno
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA.
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Hwang JT, Kim HJ, Choi HK, Park JH, Chung S, Chung MY. Butein Synergizes with Statin to Upregulate Low-Density Lipoprotein Receptor Through HNF1α-Mediated PCSK9 Inhibition in HepG2 Cells. J Med Food 2020; 23:1102-1108. [PMID: 32835593 DOI: 10.1089/jmf.2020.4761] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Downregulation of the low-density lipoprotein (LDL) receptor (LDLR) can lead to hypercholesterolemia and related conditions, including cardiovascular diseases. Statins are a class of LDL cholesterol-lowering agents and are best-selling medications for patients at high risk of developing cardiovascular diseases. Indeed, statins upregulate LDLR and proprotein convertase subtilisin/kexin type 9a (PCSK9), leading to LDLR lysosomal degradation, which interferes with the attenuation of hypercholesterolemia. In the present study, butein was found to decrease extracellular PCSK9 levels by reducing its mRNA expression, which was attributable to butein-mediated downregulation of HNF1α in HepG2 cells. Butein-mediated PCSK9 inhibition further reversed LDLR protein synthesis inhibition, which possibly occurred through butein-mediated inhibition of LDLR degradation. When treated as a combination of butein and a statin, butein reduced statin-mediated enhancement of PCSK9 protein expression. This resulted in a synergistic enhancement of LDLR protein expression, whereas butein alone marginally increased LDLR protein expression. These findings suggest that butein, a novel PCSK9 inhibitor, may be a potential alternative or adjunct to statin treatment.
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Affiliation(s)
- Jin-Taek Hwang
- Korea Food Research Institute, Wanju-Gun, Korea.,Department of Food Biotechnology, Korea University of Science & Technology, Daejeon, Korea
| | - Hyo Jin Kim
- Korea Food Research Institute, Wanju-Gun, Korea.,Department of Food Biotechnology, Korea University of Science & Technology, Daejeon, Korea
| | | | - Jae-Ho Park
- Korea Food Research Institute, Wanju-Gun, Korea
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Hodges JK, Sasaki GY, Bruno RS. Anti-inflammatory activities of green tea catechins along the gut-liver axis in nonalcoholic fatty liver disease: lessons learned from preclinical and human studies. J Nutr Biochem 2020; 85:108478. [PMID: 32801031 DOI: 10.1016/j.jnutbio.2020.108478] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 07/02/2020] [Accepted: 07/23/2020] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD), which is the most prevalent hepatic disorder worldwide, affecting 25% of the general population, describes a spectrum of progressive liver conditions ranging from relatively benign liver steatosis and advancing to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Hallmark features of NASH are fatty hepatocytes and inflammatory cell infiltrates in association with increased activation of hepatic nuclear factor kappa-B (NFκB) that exacerbates liver injury. Because no pharmacological treatments exist for NAFLD, emphasis has been placed on dietary approaches to manage NASH risk. Anti-inflammatory bioactivities of catechin-rich green tea extract (GTE) have been well-studied, especially in preclinical models that have detailed its effects on inflammatory responses downstream of NFκB activation. This review will therefore discuss the experimental evidence that has advanced an understanding of the mechanisms by which GTE, either directly through its catechins or potentially indirectly through microbiota-derived metabolites, limits NFκB activation and NASH-associated liver injury. Specifically, it will describe the hepatic-level benefits of GTE that attenuate intracellular redox distress and pro-inflammatory signaling from extracellular receptors that otherwise activate NFκB. In addition, it will discuss the anti-inflammatory activities of GTE on gut barrier function as well as prebiotic and antimicrobial effects on gut microbial ecology that help to limit the translocation of gut-derived endotoxins (e.g. lipopolysaccharides) to the liver where they otherwise upregulate NFκB activation by Toll-like receptor-4 signaling. This summary is therefore expected to advance research translation of the hepatic- and intestinal-level benefits of GTE and its catechins to help manage NAFLD-associated morbidity.
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Affiliation(s)
- Joanna K Hodges
- Human Nutrition Program, The Ohio State University, Columbus, OH 43210
| | - Geoffrey Y Sasaki
- Human Nutrition Program, The Ohio State University, Columbus, OH 43210
| | - Richard S Bruno
- Human Nutrition Program, The Ohio State University, Columbus, OH 43210.
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The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19. Antioxidants (Basel) 2020; 9:antiox9070624. [PMID: 32708578 PMCID: PMC7402141 DOI: 10.3390/antiox9070624] [Citation(s) in RCA: 144] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Revised: 07/12/2020] [Accepted: 07/14/2020] [Indexed: 02/06/2023] Open
Abstract
The novel COVID-19 pandemic is affecting the world’s population differently: mostly in the presence of conditions such as aging, diabetes and hypertension the virus triggers a lethal cytokine storm and patients die from acute respiratory distress syndrome, whereas in many cases the disease has a mild or even asymptomatic progression. A common denominator in all conditions associated with COVID-19 appears to be the impaired redox homeostasis responsible for reactive oxygen species (ROS) accumulation; therefore, levels of glutathione (GSH), the key anti-oxidant guardian in all tissues, could be critical in extinguishing the exacerbated inflammation that triggers organ failure in COVID-19. The present review provides a biochemical investigation of the mechanisms leading to deadly inflammation in severe COVID-19, counterbalanced by GSH. The pathways competing for GSH are described to illustrate the events concurring to cause a depletion of endogenous GSH stocks. Drawing on evidence from literature that demonstrates the reduced levels of GSH in the main conditions clinically associated with severe disease, we highlight the relevance of restoring GSH levels in the attempt to protect the most vulnerable subjects from severe symptoms of COVID-19. Finally, we discuss the current data about the feasibility of increasing GSH levels, which could be used to prevent and subdue the disease.
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Abstract
Objectives To investigate the neuroprotective effects of six natural compounds
(caffeine, gallic acid, resveratrol, epigallocatechin gallate [EGCG],
L-ascorbic acid and alpha tocopherol [Vitamin E] on heavy metal-induced cell
damage in rat PC12 cells. Methods In this in vitro experiment, rat PC12 cells were exposed to
four heavy metals (CdCl2, HgCl2, CoCl2 and
PbCl2) at different concentrations and cell apoptosis,
necrosis and oxidative stress were assessed with and without the addition of
the six natural compounds. Results The metals decreased cell viability but the natural compounds attenuated
their effects on apoptosis, necrosis and reactive oxygen species (ROS)
levels. Mitochondrial protein changes were involved in the regulation. Conclusion Overall, the natural compounds did provide protection against the
metal-induced PC12 cell damage. These data suggest that natural compounds
may have therapeutic potential against metal-induced neurodegenerative
disease.
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Affiliation(s)
- Lina Yang
- Changchun Medical College, Changchun, China
| | - Keshu Shen
- Hepatology Department, Jilin Hepatobiliary Hospital, Changchun, China
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30
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Hodges JK, Zhu J, Yu Z, Vodovotz Y, Brock G, Sasaki GY, Dey P, Bruno RS. Intestinal-level anti-inflammatory bioactivities of catechin-rich green tea: Rationale, design, and methods of a double-blind, randomized, placebo-controlled crossover trial in metabolic syndrome and healthy adults. Contemp Clin Trials Commun 2020; 17:100495. [PMID: 31799477 PMCID: PMC6881604 DOI: 10.1016/j.conctc.2019.100495] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Revised: 11/07/2019] [Accepted: 11/17/2019] [Indexed: 12/18/2022] Open
Abstract
Metabolic endotoxemia initiates low-grade chronic inflammation in metabolic syndrome (MetS) and provokes the progression towards more advanced cardiometabolic disorders. Our recent works in obese rodent models demonstrate that catechin-rich green tea extract (GTE) improves gut barrier integrity to alleviate the translocation of gut-derived endotoxin and its consequent pro-inflammatory responses mediated through Toll-like receptor-4/nuclear factor κB (TLR4/NFκB) signaling. The objective of this clinical trial is to establish the efficacy of GTE to alleviate metabolic endotoxemia-associated inflammation in persons with MetS by improving gut barrier function. We plan a double-blind, placebo-controlled cross-over trial in persons with MetS and age- and gender-matched healthy persons (18-65 y; n = 20/group) who will receive a low-energy GTE-rich (1 g/day; 890 mg total catechins) confection snack food while following a low-polyphenol diet for 28 days. Assessments will include measures of circulating endotoxin (primary outcome) and secondary outcomes including biomarkers of endotoxin exposure, region-specific measures of intestinal permeability, gut microbiota composition, diversity, and functions, intestinal and systemic inflammatory responses, and catechins and microbiota-derived catechin metabolites. Study outcomes will provide the first report of the GTE-mediated benefits that alleviate gut barrier dysfunction in relation to endotoxemia-associated inflammation in MetS persons. This is expected to help establish an effective dietary strategy to mitigate the growing burden of MetS that currently affects ~35% of Americans.
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Key Words
- BMI, body mass index
- Catechin
- Endotoxemia
- GTE, green tea extract
- Gut barrier function
- Gut dysbiosis
- Gut microbiota
- Inflammation
- LBP, LPS binding protein
- LPS, lipopolysaccharides
- MetS, metabolic syndrome
- Metabolic syndrome
- NFκB, nuclear factor κB
- PCoA, principal coordinates analysis
- SCFA, short chain fatty acid
- TLR4, Toll-like receptor-4
- TNF- α, tumor necrosis factor-α
- Tea
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Affiliation(s)
- Joanna K. Hodges
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA
| | - Jiangjiang Zhu
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA
- James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Zhongtang Yu
- Department of Animal Sciences, The Ohio State University, Columbus, OH, USA
| | - Yael Vodovotz
- Department of Food Science and Technology, The Ohio State University, Columbus, OH, USA
| | - Guy Brock
- Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA
| | | | - Priyankar Dey
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA
| | - Richard S. Bruno
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA
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Shen Y, Xiao X, Wu K, Wang Y, Yuan Y, Liu J, Sun S, Liu J. Effects and molecular mechanisms of Ninghong black tea extract in nonalcoholic fatty liver disease of rats. J Food Sci 2020; 85:800-807. [PMID: 32090345 DOI: 10.1111/1750-3841.14846] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2019] [Revised: 09/03/2019] [Accepted: 09/16/2019] [Indexed: 12/24/2022]
Abstract
The aim of this study is to observe the effects of Ninghong black tea extract on fat deposition and high-fat diet-induced nonalcoholic fatty liver disease (NAFLD) and to explore the potential mechanisms of these effect. Under 2% Ninghong black tea extract diet feeding in rat model, the results showed that Ninghong black tea extract decreased the body fat ratio and the number of lipid droplets in the liver and significantly alleviated NAFLD in the rat model. The real-time fluorescence quantitative polymerase chain reaction results showed that Ninghong black tea extract significantly upregulated the expression of peroxisome proliferator-activated receptor α (PPARα), which is important in fatty acid β-oxidation, and microsomal triglyceride transfer protein (MTP), which plays an important role in the synthesis of very low density lipoprotein (VLDL). By promoting the expression of PPARα and MTP in liver tissue and thereby promoting fatty acid β-oxidation and VLDL synthesis, Ninghong black tea extract relieves high-fat diet-induced NAFLD.
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Affiliation(s)
- Yu Shen
- Molecular Biology Research Center, School of Life Sciences, Central South Univ., Changsha, 410078, China
| | - Xiaojuan Xiao
- Molecular Biology Research Center, School of Life Sciences, Central South Univ., Changsha, 410078, China
| | - Kunlu Wu
- Molecular Biology Research Center, School of Life Sciences, Central South Univ., Changsha, 410078, China
| | - Yanpeng Wang
- Molecular Biology Research Center, School of Life Sciences, Central South Univ., Changsha, 410078, China
| | - Yijun Yuan
- Molecular Biology Research Center, School of Life Sciences, Central South Univ., Changsha, 410078, China
| | - Jianwei Liu
- Molecular Biology Research Center, School of Life Sciences, Central South Univ., Changsha, 410078, China
| | - Shuming Sun
- Molecular Biology Research Center, School of Life Sciences, Central South Univ., Changsha, 410078, China
| | - Jing Liu
- Molecular Biology Research Center, School of Life Sciences, Central South Univ., Changsha, 410078, China
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Sasaki GY, Li J, Cichon MJ, Riedl KM, Kopec RE, Bruno RS. Green Tea Extract Treatment in Obese Mice with Nonalcoholic Steatohepatitis Restores the Hepatic Metabolome in Association with Limiting Endotoxemia-TLR4-NFκB-Mediated Inflammation. Mol Nutr Food Res 2019; 63:e1900811. [PMID: 31574193 PMCID: PMC7293799 DOI: 10.1002/mnfr.201900811] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2019] [Revised: 09/18/2019] [Indexed: 12/15/2022]
Abstract
SCOPE Catechin-rich green tea extract (GTE) alleviates nonalcoholic steatohepatitis (NASH) by lowering endotoxin-TLR4 (Toll-like receptor-4)-NFκB (nuclear factor kappa-B) inflammation. This study aimed to define altered MS-metabolomic responses during high-fat (HF)-induced NASH that are restored by GTE utilizing livers from an earlier study in which GTE decreased endotoxin-TLR4-NFκB liver injury. METHODS AND RESULTS Mice are fed a low-fat (LF) or HF diet for 12 weeks and then randomized to LF or HF diets containing 0% or 2% GTE for an additional 8 weeks. Global MS-based metabolomics and targeted metabolite profiling of catechins/catechin metabolites are evaluated. GTE in HF mice restores hepatic metabolites implicated in dyslipidemia insulin resistance, and inflammation. These include 122 metabolites: amino acids, lipids, nucleotides, vitamins, bile acids, flavonoids, xenobiotics, and carbohydrates. Hepatic amino acids, B-vitamins, and bile acids are inversely correlated with biomarkers of insulin resistance, liver injury, steatosis, and inflammation. Further, phosphatidylcholine metabolites are positively correlated with biomarkers of liver injury and NFκB inflammation. Thirteen catechin metabolites are identified in livers of GTE-treated mice, mostly as phase II conjugates of parental catechins or microbial-derived valerolactones. CONCLUSION The defined anti-inflammatory/metabolic interactions advance an understanding of the mechanism by which GTE catechins protect against NFκB-mediated liver injury in NASH.
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Affiliation(s)
- Geoffrey Y Sasaki
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
| | - Jinhui Li
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
| | - Morgan J Cichon
- Personalized Food and Nutritional Metabolomics for Health, The Ohio State University, Columbus, OH, 43210, USA
| | - Ken M Riedl
- Nutrient and Phytochemical Analytics Shared Resource, The Ohio State University, Columbus, OH, 43210, USA
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA
| | - Rachel E Kopec
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
- Personalized Food and Nutritional Metabolomics for Health, The Ohio State University, Columbus, OH, 43210, USA
| | - Richard S Bruno
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
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Xu XY, Zheng J, Meng JM, Gan RY, Mao QQ, Shang A, Li BY, Wei XL, Li HB. Effects of Food Processing on In Vivo Antioxidant and Hepatoprotective Properties of Green Tea Extracts. Antioxidants (Basel) 2019; 8:572. [PMID: 31766414 PMCID: PMC6943518 DOI: 10.3390/antiox8120572] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Revised: 11/15/2019] [Accepted: 11/19/2019] [Indexed: 12/14/2022] Open
Abstract
Food processing can affect the nutrition and safety of foods. A previous study showed that tannase and ultrasound treatment could significantly increase the antioxidant activities of green tea extracts according to in vitro evaluation methods. Since the results from in vitro and in vivo experiments may be inconsistent, the in vivo antioxidant activities of the extracts were studied using a mouse model of alcohol-induced acute liver injury in this study. Results showed that all the extracts decreased the levels of aspartate transaminase and alanine aminotransferase in serum, reduced the levels of malondialdehyde and triacylglycerol in the liver, and increased the levels of catalase and glutathione in the liver, which can alleviate hepatic oxidative injury. In addition, the differences between treated and original extracts were not significant in vivo. In some cases, the food processing can have a negative effect on in vivo antioxidant activities. That is, although tannase and ultrasound treatment can significantly increase the antioxidant activities of green tea extracts in vitro, it cannot improve the in vivo antioxidant activities, which indicates that some food processing might not always have positive effects on products for human benefits.
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Affiliation(s)
- Xiao-Yu Xu
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (X.-Y.X.); (J.Z.); (J.-M.M.); (Q.-Q.M.); (A.S.); (B.-Y.L.)
| | - Jie Zheng
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (X.-Y.X.); (J.Z.); (J.-M.M.); (Q.-Q.M.); (A.S.); (B.-Y.L.)
| | - Jin-Ming Meng
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (X.-Y.X.); (J.Z.); (J.-M.M.); (Q.-Q.M.); (A.S.); (B.-Y.L.)
| | - Ren-You Gan
- Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu 610213, China
- Department of Food Science & Technology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China;
| | - Qian-Qian Mao
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (X.-Y.X.); (J.Z.); (J.-M.M.); (Q.-Q.M.); (A.S.); (B.-Y.L.)
| | - Ao Shang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (X.-Y.X.); (J.Z.); (J.-M.M.); (Q.-Q.M.); (A.S.); (B.-Y.L.)
| | - Bang-Yan Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (X.-Y.X.); (J.Z.); (J.-M.M.); (Q.-Q.M.); (A.S.); (B.-Y.L.)
| | - Xin-Lin Wei
- Department of Food Science & Technology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China;
| | - Hua-Bin Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (X.-Y.X.); (J.Z.); (J.-M.M.); (Q.-Q.M.); (A.S.); (B.-Y.L.)
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Dey P, Kim JB, Chitchumroonchokchai C, Li J, Sasaki GY, Olmstead BD, Stock KL, Thomas-Ahner JM, Clinton SK, Bruno RS. Green tea extract inhibits early oncogenic responses in mice with nonalcoholic steatohepatitis. Food Funct 2019; 10:6351-6361. [PMID: 31503268 DOI: 10.1039/c9fo01199d] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Nonalcoholic steatohepatitis (NASH) increases hepatocellular carcinoma (HCC) risk. We hypothesized that the hepatoprotective anti-inflammatory benefits of catechin-rich green tea extract (GTE) would protect against HCC progression by inhibiting NASH-associated liver injury and pro-oncogenic responses. We used an HCC model in high-fat (HF)-fed mice that mimics early oncogenic events during NASH without inducing tumorigenesis and premature mortality. Male C57BL/6J mice (4-weeks old) were fed a HF diet containing GTE at 0% or 2%. Mice were administered saline or diethylnitrosamine (DEN; 60 mg kg-1, i.p.) at 5-weeks and 7-weeks of age. NASH, inflammation, fibrosis, and oncogenic responses were assessed at 25-weeks of age. Saline-treated mice showed prominent histopathological signs of steatosis and hepatocellular ballooning. Although DEN did not impact adiposity, steatosis, ballooning and hepatic lipid accumulation, these parameters were attenuated by GTE regardless of DEN. Hepatic lipid peroxidation and fibrosis that were increased by DEN were attenuated by GTE. Hepatic TLR4, MCP1 and TNFα mRNA levels were unaffected by DEN, whereas iNOS was increased by DEN. These transcripts were lowered by GTE. GTE attenuated the frequency of PCNA+ hepatocytes and mRNA expression of cyclin D1, MIB1 and Ki-67 that were otherwise increased by DEN. GTE increase APAF1 mRNA that was otherwise lowered by DEN. Relative to saline-treated mice, DEN increased mRNA levels of oncostatin M, gp130, c-Fos, c-Myc and survivin; each was lowered by GTE in DEN-treated mice. These findings indicate that GTE may protect against hepatic oncogenesis by limiting early steps in the carcinogenic cascade related to NASH-associated HCC.
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Affiliation(s)
- Priyankar Dey
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA.
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Rha CS, Jeong HW, Park S, Lee S, Jung YS, Kim DO. Antioxidative, Anti-Inflammatory, and Anticancer Effects of Purified Flavonol Glycosides and Aglycones in Green Tea. Antioxidants (Basel) 2019; 8:E278. [PMID: 31387266 PMCID: PMC6719943 DOI: 10.3390/antiox8080278] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Revised: 07/27/2019] [Accepted: 08/01/2019] [Indexed: 12/12/2022] Open
Abstract
(1) Background: Extensive research has focused on flavan-3-ols, but information about the bioactivities of green tea flavonols is limited. (2) Methods: In this study, we investigated the antioxidative, anti-inflammatory, and anticancer effects of flavonol glycosides and aglycones from green tea using in vitro cell models. The fractions rich in flavonol glycoside (FLG) and flavonol aglycone (FLA) were obtained from green tea extract after treatment with tannase and cellulase, respectively. (3) Results: FLG and FLA contained 16 and 13 derivatives, respectively, including apigenin, kaempferol, myricetin, and quercetin, determined by mass spectrometry. FLA exhibited higher radical-scavenging activity than that of FLG. FLG and FLA attenuated the levels of intracellular oxidative stress in neuron-like PC-12 cells. The treatment of RAW 264.7 murine macrophages with FLG and FLA significantly reduced the mRNA expression of inflammation-related genes in a dose-dependent manner. Furthermore, FLG and FLA treatments decreased the viability of the colon adenoma cell line DLD-1 and breast cancer cell line E0771. Moreover, the treatment with FLG or FLA combined with paclitaxel had synergistic anticancer effects on the DLD-1 cell line. (4) Conclusions: Flavonols from green tea exerted beneficial effects on health and may be superior to flavan-3-ols.
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Affiliation(s)
- Chan-Su Rha
- Vitalbeautie Research Division, Amorepacific Corporation R&D Center, Yongin 17074, Korea
| | - Hyun Woo Jeong
- Vitalbeautie Research Division, Amorepacific Corporation R&D Center, Yongin 17074, Korea
| | - Saitbyul Park
- Safety and Regulatory Division, Amorepacific Corporation R&D Center, Yongin 17074, Korea
| | - Siyoung Lee
- Precision Medicine Research Center, Advanced Institutes of Convergence Technology, Suwon 16229, Korea
| | - Young Sung Jung
- Department of Food Science and Biotechnology, Kyung Hee University, Yongin 17104, Korea
| | - Dae-Ok Kim
- Department of Food Science and Biotechnology, Kyung Hee University, Yongin 17104, Korea.
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Zhou J, Ho CT, Long P, Meng Q, Zhang L, Wan X. Preventive Efficiency of Green Tea and Its Components on Nonalcoholic Fatty Liver Disease. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:5306-5317. [PMID: 30892882 DOI: 10.1021/acs.jafc.8b05032] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a typical chronic liver disease highly correlated with metabolic syndrome. Growing prevalence of NAFLD is supposed to be linked with the unhealthy lifestyle, especially high-calorie diet and lacking enough exercise. Currently, there is no validated pharmacological therapy for NAFLD except for weight reduction. However, many dietary strategies had preventive effects on the development of liver steatosis or its progression. As one of the most common beverages, green tea contains abundant bioactive compounds possessing antioxidant, lipid-lowering, and anti-inflammatory effects, as well as improving insulin resistance and gut dysbiosis that can alleviate the risk of NAFLD. Hence, in this review, we summarized the studies of green tea and its components on NAFLD from animal experiments and human interventions and discussed the potential mechanisms. Available evidence suggested that tea consumption is promising to prevent NAFLD, and further mechanisms and clinical studies need to be investigated.
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Affiliation(s)
| | - Chi-Tang Ho
- Department of Food Science , Rutgers University , New Brunswick , New Jersey , United States
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Dey P, Sasaki GY, Wei P, Li J, Wang L, Zhu J, McTigue D, Yu Z, Bruno RS. Green tea extract prevents obesity in male mice by alleviating gut dysbiosis in association with improved intestinal barrier function that limits endotoxin translocation and adipose inflammation. J Nutr Biochem 2019; 67:78-89. [PMID: 30856467 DOI: 10.1016/j.jnutbio.2019.01.017] [Citation(s) in RCA: 101] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Revised: 01/03/2019] [Accepted: 01/29/2019] [Indexed: 01/03/2023]
Abstract
Gut-derived endotoxin translocation provokes obesity by inducing TLR4/NFκB inflammation. We hypothesized that catechin-rich green tea extract (GTE) would protect against obesity-associated TLR4/NFκB inflammation by alleviating gut dysbiosis and limiting endotoxin translocation. Male C57BL/6J mice were fed a low-fat (LF) or high-fat (HF) diet containing 0% or 2% GTE for 8 weeks. At Week 7, fluorescein isothiocyanate (FITC)-dextran was administered by oral gavage before assessing its serum concentrations as a gut permeability marker. HF-feeding increased (P<.05) adipose mass and adipose expression of genes involved in TLR4/NFκB-dependent inflammation and macrophage activation. GTE attenuated HF-induced obesity and pro-inflammatory gene expression. GTE in HF mice decreased serum FITC-dextran, and attenuated portal vein and circulating endotoxin concentrations. GTE in HF mice also prevented HF-induced decreases in the expression of intestinal tight junction proteins (TJPs) and hypoxia inducible factor-1α while preventing increases in TLR4/NFκB-dependent inflammatory genes. Gut microbial diversity was increased, and the Firmicutes:Bacteroidetes ratio was decreased, in HF mice fed GTE compared with HF controls. GTE in LF mice did not attenuate adiposity but decreased endotoxin and favorably altered several gut bacterial populations. Serum FITC-dextran was correlated with portal vein endotoxin (P<.001; rP=0.66) and inversely correlated with colonic mRNA levels of TJPs (P<.05; rP=-0.38 to -0.48). Colonic TJPs mRNA were inversely correlated with portal endotoxin (P<.05; rP=-0.33 to -0.39). These data suggest that GTE protects against diet-induced obesity consistent with a mechanism involving the gut-adipose axis that limits endotoxin translocation and consequent adipose TLR4/NFκB inflammation by improving gut barrier function.
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Affiliation(s)
- Priyankar Dey
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA
| | - Geoffrey Y Sasaki
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA
| | - Ping Wei
- Department of Neuroscience and Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, OH, USA
| | - Jinhui Li
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA
| | - Lingling Wang
- Department of Animal Sciences, The Ohio State University, Columbus, OH, USA
| | - Jiangjiang Zhu
- Department of Chemistry and Biochemistry, Miami University, Oxford, OH, USA
| | - Dana McTigue
- Department of Neuroscience and Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, OH, USA
| | - Zhongtang Yu
- Department of Animal Sciences, The Ohio State University, Columbus, OH, USA
| | - Richard S Bruno
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA.
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38
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Tête A, Gallais I, Imran M, Chevanne M, Liamin M, Sparfel L, Bucher S, Burel A, Podechard N, Appenzeller BMR, Fromenty B, Grova N, Sergent O, Lagadic-Gossmann D. Mechanisms involved in the death of steatotic WIF-B9 hepatocytes co-exposed to benzo[a]pyrene and ethanol: a possible key role for xenobiotic metabolism and nitric oxide. Free Radic Biol Med 2018; 129:323-337. [PMID: 30268890 DOI: 10.1016/j.freeradbiomed.2018.09.042] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Revised: 09/20/2018] [Accepted: 09/26/2018] [Indexed: 12/15/2022]
Abstract
We previously demonstrated that co-exposing pre-steatotic hepatocytes to benzo[a]pyrene (B[a]P), a carcinogenic environmental pollutant, and ethanol, favored cell death. Here, the intracellular mechanisms underlying this toxicity were studied. Steatotic WIF-B9 hepatocytes, obtained by a 48h-supplementation with fatty acids, were then exposed to B[a]P/ethanol (10 nM/5 mM, respectively) for 5 days. Nitric oxide (NO) was demonstrated to be a pivotal player in the cell death caused by the co-exposure in steatotic hepatocytes. Indeed, by scavenging NO, CPTIO treatment of co-exposed steatotic cells prevented not only the increase in DNA damage and cell death, but also the decrease in the activity of CYP1, major cytochrome P450s of B[a]P metabolism. This would then lead to an elevation of B[a]P levels, thus possibly suggesting a long-lasting stimulation of the transcription factor AhR. Besides, as NO can react with superoxide anion to produce peroxynitrite, a highly oxidative compound, the use of FeTPPS to inhibit its formation indicated its participation in DNA damage and cell death, further highlighting the important role of NO. Finally, a possible key role for AhR was pointed out by using its antagonist, CH-223191. Indeed it prevented the elevation of ADH activity, known to participate to the ethanol production of ROS, notably superoxide anion. The transcription factor, NFκB, known to be activated by ROS, was shown to be involved in the increase in iNOS expression. Altogether, these data strongly suggested cooperative mechanistic interactions between B[a]P via AhR and ethanol via ROS production, to favor cell death in the context of prior steatosis.
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Affiliation(s)
- Arnaud Tête
- Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France
| | - Isabelle Gallais
- Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France
| | - Muhammad Imran
- Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France
| | - Martine Chevanne
- Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France
| | - Marie Liamin
- Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France
| | - Lydie Sparfel
- Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France
| | - Simon Bucher
- Univ Rennes, Inserm, Inra, Institut NUMECAN (Nutrition Metabolisms and Cancer) - UMR_S 1241, UMR_A 1341, F-35000 Rennes, France
| | - Agnès Burel
- Univ Rennes, Biosit - UMS 3480, US_S 018, F-35000 Rennes, France
| | - Normand Podechard
- Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France
| | - Brice M R Appenzeller
- HBRU, Luxembourg Institute of Health, 29, rue Henri Koch, L-4354 Esch-sur-Alzette, Luxembourg
| | - Bernard Fromenty
- Univ Rennes, Inserm, Inra, Institut NUMECAN (Nutrition Metabolisms and Cancer) - UMR_S 1241, UMR_A 1341, F-35000 Rennes, France
| | - Nathalie Grova
- HBRU, Luxembourg Institute of Health, 29, rue Henri Koch, L-4354 Esch-sur-Alzette, Luxembourg
| | - Odile Sergent
- Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France
| | - Dominique Lagadic-Gossmann
- Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France.
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Goodus MT, Sauerbeck AD, Popovich PG, Bruno RS, McTigue DM. Dietary Green Tea Extract Prior to Spinal Cord Injury Prevents Hepatic Iron Overload but Does Not Improve Chronic Hepatic and Spinal Cord Pathology in Rats. J Neurotrauma 2018; 35:2872-2882. [PMID: 30084733 DOI: 10.1089/neu.2018.5771] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Spinal cord injury (SCI) disrupts autonomic regulation of visceral organs. As a result, a leading cause of mortality in the SCI population is metabolic dysfunction, and an organ central to metabolic control is the liver. Our recent work showed that rodent SCI promotes Kupffer cell (hepatic macrophage) activation, pro-inflammatory cytokine expression, and liver steatosis. These are symptoms of nonalcoholic steatohepatitis (NASH), the hepatic manifestation of metabolic syndrome, and these pre-clinical data replicate aspects of post-SCI human metabolic dysfunction. Because metabolic profile is highly dependent on lifestyle, including diet, it is likely that lifestyle choices prior to injury influence metabolic and hepatic outcomes after SCI. Therefore, in this study we tested if a diet rich in green tea extract (GTE), a known hepatoprotective agent, that began 3 weeks before SCI and was maintained after injury, reduced indices of liver pathology or metabolic dysfunction. GTE treatment significantly reduced post-SCI hepatic iron accumulation and blunted circulating glucose elevation compared with control-diet rats. However, GTE pre-treatment did not prevent Kupffer cell activation, hepatic lipid accumulation, increased serum alanine transaminase, or circulating non-esterified fatty acids, which were all significantly increased 6 weeks post-injury. Spinal cord pathology also was unchanged by GTE. Thus, dietary GTE prior to and after SCI had only a minor hepatoprotective effect. In general, for optimal health of SCI individuals, it will be important for future studies to evaluate how other lifestyle choices made before or after SCI positively or negatively impact systemic and intraspinal outcomes and the overall metabolic health of SCI individuals.
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Affiliation(s)
- Matthew T Goodus
- 1 The Center for Brain and Spinal Cord Repair, College of Education and Human Ecology, The Ohio State University, Columbus, Ohio.,2 Department of Neuroscience, College of Education and Human Ecology, The Ohio State University, Columbus, Ohio.,3 Belford Center for Spinal Cord Injury, Wexner Medical Center, College of Education and Human Ecology, The Ohio State University, Columbus, Ohio
| | - Andrew D Sauerbeck
- 1 The Center for Brain and Spinal Cord Repair, College of Education and Human Ecology, The Ohio State University, Columbus, Ohio.,2 Department of Neuroscience, College of Education and Human Ecology, The Ohio State University, Columbus, Ohio
| | - Phillip G Popovich
- 1 The Center for Brain and Spinal Cord Repair, College of Education and Human Ecology, The Ohio State University, Columbus, Ohio.,2 Department of Neuroscience, College of Education and Human Ecology, The Ohio State University, Columbus, Ohio.,3 Belford Center for Spinal Cord Injury, Wexner Medical Center, College of Education and Human Ecology, The Ohio State University, Columbus, Ohio
| | - Richard S Bruno
- 4 Human Nutrition Program, College of Education and Human Ecology, The Ohio State University, Columbus, Ohio
| | - Dana M McTigue
- 1 The Center for Brain and Spinal Cord Repair, College of Education and Human Ecology, The Ohio State University, Columbus, Ohio.,2 Department of Neuroscience, College of Education and Human Ecology, The Ohio State University, Columbus, Ohio.,3 Belford Center for Spinal Cord Injury, Wexner Medical Center, College of Education and Human Ecology, The Ohio State University, Columbus, Ohio
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40
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Depletion of regulator-of-G-protein signaling-10 in mice exaggerates high-fat diet-induced insulin resistance and inflammation, and this effect is mitigated by dietary green tea extract. Nutr Res 2018; 70:50-59. [PMID: 30032988 DOI: 10.1016/j.nutres.2018.06.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 06/11/2018] [Accepted: 06/24/2018] [Indexed: 12/25/2022]
Abstract
The interaction between insulin resistance and inflammation plays a central role in the development of chronic diseases, although the mechanism is not fully understood. We previously demonstrated that regulator of G-protein signaling-10 (RGS10) protein is a negative modulator of the inflammatory response in macrophages and microglia. Because inflammation is a critical component in the development of high fat diet-induced insulin resistance, in this study we investigated whether RGS10 is involved in the diet-dependent regulation of glucose tolerance and insulin sensitivity. We hypothesized that the absence of RGS10 would exaggerate high-fat diet (HFD)-induced insulin resistance and inflammation response. Our results showed that RGS10 knockout (KO) mice fed a HFD gained significantly more weight and developed severe insulin resistance compared to wild-type (WT) mice fed HFD. Furthermore, compared to WT HFD-fed mice, KO mice fed the HFD displayed inflammatory phenotypes such as decreased adipose tissue expression of the anti-inflammatory M2 markers YM1 and Fizz1 and increased expression of the proinflammatory M1 cytokine interleukin 6 in adipose and CD11b, CD68 and interleukin 1β in liver tissues. The impact of RGS10 deficiency on the exaggeration of HFD-induced insulin resistance and inflammation was ameliorated by oral consumption of green tea extract. Our results demonstrate that RGS10 is an important part of a protective mechanism involved in in regulating metabolic homeostasis by reducing inflammatory responses, which could potentially lead to an innovative new approach targeting inflammation and insulin resistance.
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Choi HK, Hwang JT, Nam TG, Kim SH, Min DK, Park SW, Chung MY. Welsh onion extract inhibits PCSK9 expression contributing to the maintenance of the LDLR level under lipid depletion conditions of HepG2 cells. Food Funct 2018; 8:4582-4591. [PMID: 29130084 DOI: 10.1039/c7fo00562h] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Statins mediate the transactivation of PCSK9, which in turn limits their cholesterol-lowering effects via LDL receptor (LDLR) degradation. The objective of the present study was to investigate the mechanism of action by which Welsh onion (Allium fistulosum L. [family Amaryllidaceae]) extract (WOE) regulates LDLR and PCSK9. HepG2 cells were cultured under lipid depletion conditions using a medium supplemented with delipidated serum (DLPS). WOE (50, 100, 200, and 400 μg ml-1) significantly attenuated the DLPS-mediated increases in LDLR, PCSK9, and SREBP2 gene expression. While WOE treatment maintained the DLPS-mediated increases in LDLR protein expression, it dose-dependently and significantly attenuated the DLPS-mediated increases in the protein content of PCSK9. The suppression of PCSK9 was associated with the WOE-mediated reductions in SREBP2, but not HNF1α. WOE also dose-dependently reduced PCSK9 protein expression that was otherwise markedly induced by concomitant statin treatment. WOE-mediated PCSK9 inhibition contributed to LDLR lysosomal degradation suppression, and subsequent LDLR protein stabilization. HPLC analysis indicated that WOE contains kaempferol, quercetin, ferulic acid, and p-coumaric acid. Kaempferol and p-coumaric acid contributed to the maintenance of LDLR expression by inhibiting PCSK9 in lipid depleted HepG2 cells. Altogether, these findings suggest that WOE inhibits PCSK9 transcription and protein expression via the reduction of SREBP2, and decreased PCSK9 further contributes to LDLR degradation prevention and LDLR protein stabilization under conditions of lipoprotein deficiency. The PCSK9 inhibition-mediated mechanism of WOE was likely attributed to the action of kaempferol and p-coumaric acid present in WOE.
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Affiliation(s)
- Hyo-Kyoung Choi
- Korea Food Research Institute, Seongnam City, Republic of Korea.
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42
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Awika JM, Rose DJ, Simsek S. Complementary effects of cereal and pulse polyphenols and dietary fiber on chronic inflammation and gut health. Food Funct 2018. [PMID: 29532826 DOI: 10.1039/c7fo02011b] [Citation(s) in RCA: 93] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Cereal grains and grain pulses are primary staples often consumed together, and contribute a major portion of daily human calorie and protein intake globally. Protective effects of consuming whole grain cereals and grain pulses against various inflammation-related chronic diseases are well documented. However, potential benefits of combined intake of whole cereals and pulses beyond their complementary amino acid nutrition is rarely considered in literature. There is ample evidence that key bioactive components of whole grain cereals and pulses are structurally different and thus may be optimized to provide synergistic/complementary health benefits. Among the most important whole grain bioactive components are polyphenols and dietary fiber, not only because of their demonstrated biological function, but also their major impact on consumer choice of whole grain/pulse products. This review highlights the distinct structural differences between key cereal grain and pulse polyphenols and non-starch polysaccharides (dietary fiber), and the evidence on specific synergistic/complementary benefits of combining the bioactive components from the two commodities. Interactive effects of the polyphenols and fiber on gut microbiota and associated benefits to colon health, and against systemic inflammation, are discussed. Processing technologies that can be used to further enhance the interactive benefits of combined cereal-pulse bioactive compounds are highlighted.
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Affiliation(s)
- Joseph M Awika
- Cereal Quality Laboratory, Soil & Crop Science Department, Texas A&M University, College Station, Texas, USA. and Nutrition and Food Science Department, Texas A&M University, College Station, Texas, USA
| | - Devin J Rose
- Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE, USA and Department of Agronomy and Horticulture, University of Nebraska-Lincoln, Lincoln, NE, USA
| | - Senay Simsek
- North Dakota State University, Department of Plant Sciences, Fargo, ND 58105, USA
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43
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Li J, Sasaki GY, Dey P, Chitchumroonchokchai C, Labyk AN, McDonald JD, Kim JB, Bruno RS. Green tea extract protects against hepatic NFκB activation along the gut-liver axis in diet-induced obese mice with nonalcoholic steatohepatitis by reducing endotoxin and TLR4/MyD88 signaling. J Nutr Biochem 2018; 53:58-65. [PMID: 29190550 DOI: 10.1016/j.jnutbio.2017.10.016] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Revised: 10/12/2017] [Accepted: 10/25/2017] [Indexed: 12/12/2022]
Abstract
Green tea extract (GTE) reduces NFκB-mediated inflammation during nonalcoholic steatohepatitis (NASH). We hypothesized that its anti-inflammatory activities would be mediated in a Toll-like receptor 4 (TLR4)-dependent manner. Wild-type (WT) and loss-of-function TLR4-mutant (TLR4m) mice were fed a high-fat diet containing GTE at 0 or 2% for 8 weeks before assessing NASH, NFκB-mediated inflammation, TLR4 and its adaptor proteins MyD88 and TRIF, circulating endotoxin, and intestinal tight junction protein mRNA expression. TLR4m mice had lower (P<.05) body mass compared with WT mice but similar adiposity, whereas body mass and adiposity were lowered by GTE regardless of genotype. Liver steatosis, serum alanine aminotransferase, and hepatic lipid peroxidation were also lowered by GTE in WT mice, and were similarly lowered in TLR4m mice regardless of GTE. Phosphorylation of the NFκB p65 subunit and pro-inflammatory genes (TNFα, iNOS, MCP-1, MPO) were lowered by GTE in WT mice, and did not differ from the lowered levels in TLR4m mice regardless of GTE. TLR4m mice had lower TLR4 mRNA, which was also lowered by GTE in both genotypes. TRIF expression was unaffected by genotype and GTE, whereas MyD88 was lower in mice fed GTE regardless of genotype. Serum endotoxin was similarly lowered by GTE regardless of genotype. Tight junction protein mRNA levels were unaffected by genotype. However, GTE similarly increased claudin-1 mRNA in the duodenum and jejunum and mRNA levels of occludin and zonula occluden-1 in the jejunum and ileum. Thus, GTE protects against inflammation during NASH, likely by limiting gut-derived endotoxin translocation and TLR4/MyD88/NFκB activation.
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Affiliation(s)
- Jinhui Li
- Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA
| | - Geoffrey Y Sasaki
- Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA
| | - Priyankar Dey
- Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA
| | | | - Allison N Labyk
- Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA
| | - Joshua D McDonald
- Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA
| | - Joshua B Kim
- Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA
| | - Richard S Bruno
- Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA.
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Miyaoka Y, Jin D, Tashiro K, Masubuchi S, Ozeki M, Hirokawa F, Hayashi M, Takai S, Uchiyama K. A novel hamster nonalcoholic steatohepatitis model induced by a high-fat and high-cholesterol diet. Exp Anim 2018; 67:239-247. [PMID: 29311502 PMCID: PMC5955755 DOI: 10.1538/expanim.17-0126] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Nonalcoholic steatohepatitis (NASH), in which there is steatosis and fibrosis in the
liver, is linked to metabolic syndrome and progresses to hepatic cirrhosis. In this study,
a novel hamster NASH model derived from metabolic syndrome was made using hamsters.
Hamsters were fed a normal or a high-fat and high-cholesterol (HFC) diet for 12 weeks.
Body weight and the ratio of liver weight to body weight were significantly greater in HFC
diet-fed hamsters than in normal diet-fed hamsters. Triglyceride, low-density lipoprotein
cholesterol, and glucose levels in blood were significantly increased in HFC diet-fed
hamsters, and blood pressure also tended to be high, suggesting that the HFC diet-fed
hamsters developed metabolic syndrome. Hepatic steatosis and fibrosis were observed in
liver sections of HFC diet-fed hamsters, as in patients with NASH, but they were not seen
in normal diet-fed hamsters. Chymase generates angiotensin II and transforming growth
factor (TGF)-β, both of which are related to hepatic steatosis and fibrosis, and a
significant augmentation of chymase activity was observed in livers from HFC diet-fed
hamsters. Both angiotensin II and TGF-β were also significantly increased in livers of HFC
diet-fed hamsters. Thus, HFC diet-fed hamsters might develop metabolic syndrome-derived
NASH that clinically resembles that in NASH patients.
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Affiliation(s)
- Yuta Miyaoka
- Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan
| | - Denan Jin
- Department of Innovative Medicine, Graduate School of Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan
| | - Keitaro Tashiro
- Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan
| | - Shinsuke Masubuchi
- Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan
| | - Maiko Ozeki
- Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan
| | - Fumitoshi Hirokawa
- Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan
| | - Michihiro Hayashi
- Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan
| | - Shinji Takai
- Department of Innovative Medicine, Graduate School of Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan
| | - Kazuhisa Uchiyama
- Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan
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45
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Chung MY, Shin EJ, Choi HK, Kim SH, Sung MJ, Park JH, Hwang JT. Schisandra chinensis berry extract protects against steatosis by inhibiting histone acetylation in oleic acid–treated HepG2 cells and in the livers of diet-induced obese mice. Nutr Res 2017; 46:1-10. [DOI: 10.1016/j.nutres.2017.07.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Revised: 05/26/2017] [Accepted: 07/17/2017] [Indexed: 01/01/2023]
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46
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Dietary Flaxseed Oil Prevents Western-Type Diet-Induced Nonalcoholic Fatty Liver Disease in Apolipoprotein-E Knockout Mice. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2017; 2017:3256241. [PMID: 29081885 PMCID: PMC5610846 DOI: 10.1155/2017/3256241] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/15/2017] [Revised: 06/28/2017] [Accepted: 07/05/2017] [Indexed: 02/08/2023]
Abstract
The prevalence of nonalcoholic fatty liver disease (NAFLD) has dramatically increased globally during recent decades. Intake of n-3 polyunsaturated fatty acids (PUFAs), mainly eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3), is believed to be beneficial to the development of NAFLD. However, little information is available with regard to the effect of flaxseed oil rich in α-linolenic acid (ALA, C18:3n-3), a plant-derived n-3 PUFA, in improving NAFLD. This study was to gain the effect of flaxseed oil on NAFLD and further investigate the underlying mechanisms. Apolipoprotein-E knockout (apoE-KO) mice were given a normal chow diet, a western-type high-fat and high-cholesterol diet (WTD), or a WTD diet containing 10% flaxseed oil (WTD + FO) for 12 weeks. Our data showed that consumption of flaxseed oil significantly improved WTD-induced NAFLD, as well as ameliorated impaired lipid homeostasis, attenuated oxidative stress, and inhibited inflammation. These data were associated with the modification effects on expression levels of genes involved in de novo fat synthesis (SREBP-1c, ACC), triacylglycerol catabolism (PPARα, CPT1A, and ACOX1), inflammation (NF-κB, IL-6, TNF-α, and MCP-1), and oxidative stress (ROS, MDA, GSH, and SOD).
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47
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Cheng H, Xu N, Zhao W, Su J, Liang M, Xie Z, Wu X, Li Q. (-)-Epicatechin regulates blood lipids and attenuates hepatic steatosis in rats fed high-fat diet. Mol Nutr Food Res 2017; 61. [PMID: 28734036 DOI: 10.1002/mnfr.201700303] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Revised: 07/18/2017] [Accepted: 07/19/2017] [Indexed: 12/23/2022]
Abstract
SCOPE (-)-Epicatechin (EC) is a natural flavanol monomer found in cocoa, green tea, and a variety of other plant foods. In this study, effects of EC on blood lipids and hepatic steatosis, and the underlying mechanisms were investigated. METHODS AND RESULTS A hyperlipidemic rat model was induced by high-fat, high-cholesterol diet. EC was then administrated to the animals by gavage at doses of 10, 20, 40 mg/kg body weight (BW) for 12 weeks. Simvastatin was included as a positive control. The results showed that EC significantly reduced total cholesterol, LDL cholesterol and triglyceride, alleviated liver fat accumulation, while increased HDL cholesterol, in hyperlipidemic rats. EC also reduced lipid peroxidation, inhibited the pro-inflammatory cytokines, and lowered serum AST and ALT. The potential molecular mechanisms of EC underlying these effects were proposed to be associated to regulating Insig-1-SREBP-SCAP pathway, and other lipid metabolic related genes including LXR-α, FAS, and SIRT1. CONCLUSION EC effectively improved blood lipid profile and protected liver from accumulating excessive fat in hyperlipidemic rats. The results shed a light on the potential role of EC as a promising natural product in preventing hyperlipidemia and nonalcoholic fatty liver disease.
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Affiliation(s)
- Hui Cheng
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Province Key Laboratory of R&D of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Na Xu
- State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei, Anhui, China
| | - Wenxia Zhao
- Department of Gastroenterology, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
| | - Jingjing Su
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Province Key Laboratory of R&D of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Mengru Liang
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Province Key Laboratory of R&D of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Zhongwen Xie
- State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei, Anhui, China
| | - Xianli Wu
- Nutrient Data Laboratory, USDA ARS Beltsville Human Nutrition Research Center, Beltsville, MD, USA
| | - Qinglin Li
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Province Key Laboratory of R&D of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, Anhui, China
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48
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Francisqueti FV, Nascimento AF, Minatel IO, Dias MC, Luvizotto RDAM, Berchieri-Ronchi C, Ferreira ALA, Corrêa CR. Metabolic syndrome and inflammation in adipose tissue occur at different times in animals submitted to a high-sugar/fat diet. J Nutr Sci 2017; 6:e41. [PMID: 29152245 PMCID: PMC5672321 DOI: 10.1017/jns.2017.42] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Revised: 05/23/2017] [Accepted: 06/29/2017] [Indexed: 12/16/2022] Open
Abstract
Obesity is associated with low-grade inflammation, triggered in adipose tissue, which may occur due to an excess of SFA from the diet that can be recognised by Toll-like receptor-4. This condition is involved in the development of components of the metabolic syndrome associated with obesity, especially insulin resistance. The aim of the study was to evaluate the manifestation of the metabolic syndrome and adipose tissue inflammation as a function of the period of time in which rats were submitted to a high-sugar/fat diet (HSF). Male Wistar rats were divided into six groups to receive the control diet (C) or the HSF for 6, 12 or 24 weeks. HSF increased the adiposity index in all HSF groups compared with the C group. HSF was associated with higher plasma TAG, glucose, insulin and leptin levels. Homeostasis model assessment increased in HSF compared with C rats at 24 weeks. Both TNF-α and IL-6 were elevated in the epididymal adipose tissue of HSF rats at 24 weeks compared with HSF at 6 weeks and C at 24 weeks. Only the HSF group at 24 weeks showed increased expression of both Toll-like receptor-4 and NF-κB. More inflammatory cells were found in the HSF group at 24 weeks. We can conclude that the metabolic syndrome occurs independently of the inflammatory response in adipose tissue and that inflammation is associated with hypertrophy of adipocytes, which varies according to duration of exposure to the HSF.
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Affiliation(s)
| | | | - Igor Otávio Minatel
- São Paulo State University, Institute of Bioscience, Botucatu, São Paulo, Brazil
| | - Marcos Correa Dias
- Institute of Health Sciences, Federal University of Mato Grosso (UFMT), Sinop, Mato Grosso, Brazil
| | | | | | - Ana Lúcia A. Ferreira
- São Paulo State University (UNESP), Botucatu Medical School, Botucatu, São Paulo, Brazil
| | - Camila Renata Corrêa
- São Paulo State University (UNESP), Botucatu Medical School, Botucatu, São Paulo, Brazil
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Sahin K, Orhan C, Akdemir F, Tuzcu M, Sahin N, Yılmaz I, Juturu V. β-Cryptoxanthin ameliorates metabolic risk factors by regulating NF-κB and Nrf2 pathways in insulin resistance induced by high-fat diet in rodents. Food Chem Toxicol 2017; 107:270-279. [PMID: 28689061 DOI: 10.1016/j.fct.2017.07.008] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Revised: 07/03/2017] [Accepted: 07/04/2017] [Indexed: 12/18/2022]
Abstract
The aim of this experiment was to determine the effects of β-cryptoxanthin (BCX) on the cardiometabolic health risk factors and NF-κB and Nrf2 pathway in insulin resistance induced by high-fat diet (HFD) in rodents. Twenty-eight Sprague-Dawley rats were allocated into four groups: (1) Control, rats fed a standard diet for 12 weeks; (2) BCX, rats fed a standard diet and supplemented with BCX (2.5 mg/kg BW) for 12 weeks; (3) HFD, rats fed a HFD for 12 weeks, (4) HFD + BCX, rats fed a HFD and supplemented with BCX for 12 weeks. BCX reduced cardio-metabolic health markers and decreased inflammatory markers (P < 0.001). Rats fed a HFD had the lower total antioxidant capacity and antioxidant enzymes activities and higher MDA concentration than control rats (P < 0.001 for all). Comparing with the HFD group, BCX in combination with HFD inhibited liver NF-κB and TNF-α expression by 22% and 14% and enhanced liver Nrf2, HO-1, PPAR-α, and p-IRS-1 by 1.43, 1.41, 3.53, and 1.33 fold, respectively (P < 0.001). Furthermore, in adipose tissue, BCX up-regulated Nrf2, HO-1, PPAR-α, and p-IRS-1 expression, whereas, down-regulated NF-κB and TNF-α expression. In conclusion, BCX decreased visceral fat and cardiometabolic health risk factors through modulating expressions of nuclear transcription factors.
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Affiliation(s)
- Kazim Sahin
- Firat University, Department of Animal Nutrition, Elazig, Turkey.
| | - Cemal Orhan
- Firat University, Department of Animal Nutrition, Elazig, Turkey
| | - Fatih Akdemir
- Department of Nutrition, Faculty of Fisheries, Inonu University, Malatya, Turkey
| | - Mehmet Tuzcu
- Firat University, Department of Biology, Elazig, Turkey
| | - Nurhan Sahin
- Firat University, Department of Animal Nutrition, Elazig, Turkey
| | - Ismet Yılmaz
- Department of Pharmacology, Faculty of Pharmacy, Inonu University, Malatya, Turkey
| | - Vijaya Juturu
- OmniActive Health Technologies Inc., Department of Clinical Affairs, Morristown, USA
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50
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Hwang JT, Choi HK, Kim SH, Chung S, Hur HJ, Park JH, Chung MY. Hypolipidemic Activity of Quercus acutissima Fruit Ethanol Extract is Mediated by Inhibition of Acetylation. J Med Food 2017; 20:542-549. [PMID: 28581876 DOI: 10.1089/jmf.2016.3912] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
The acetylation of histone and nonhistone proteins is associated with adipogenesis. The objective of the present study was to investigate whether an ethanol extract of Quercus acutissima fruit (QF) exhibits antiobesity effects through inhibition of acetylation in 3T3-L1 preadipocytes and high fat diet (HFD)-fed obese mice. We observed that QF acts as a histone acetyltransferase (HAT) inhibitor and that QF (400 μg/mL) markedly inhibits the activity of p300 and CREB-binding protein. QF (200 μg/mL) significantly attenuated lipid accumulation without apparent toxicity, which is likely attributable to a decrease in the expressions of lipogenic proteins, including fatty acid synthase, peroxisome proliferator-activated receptor gamma, sterol regulatory element-binding protein 1, and CCAAT-enhancer-binding proteins alpha that were otherwise increased by MDI (a hormonal cocktail containing methyl isobutylmethylxanthine, dexamethasone, and insulin). MDI increased the acetylation of total lysine residues in whole 3T3-L1 cell lysate, an effect that was reversed by QF treatment (200 μg/mL). To further confirm the antiobesity activity of QF, mice were fed with HFD supplemented with QF at 50 and 200 mg/kg body weight. Mice fed with HFD exhibited increased masses of body, liver, and retroperitoneal fat, an effect that was suppressed in the presence of QF supplementation. QF-mediated decreases in body weight were attributable to a decrease in the average size of lipid droplets, as well as lipid accumulation in retroperitoneal fat and the liver, respectively. QF-mediated reductions in the size of the lipid droplets in the retroperitoneal fat tissue were likely associated with decreased expression of DGAT2. Taken together, our observations suggest that QF acts as an HAT inhibitor and attenuates adipogenesis in 3T3-L1 preadipocytes, resulting in the mitigation of HFD-induced obesity.
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Affiliation(s)
- Jin-Taek Hwang
- 1 Korea Food Research Institute , Seongnam, Korea.,2 Department of Food Biotechnology, Korea University of Science & Technology , Daejeon, Korea
| | | | - Sung Hee Kim
- 1 Korea Food Research Institute , Seongnam, Korea
| | | | | | - Jae Ho Park
- 1 Korea Food Research Institute , Seongnam, Korea.,2 Department of Food Biotechnology, Korea University of Science & Technology , Daejeon, Korea
| | - Min-Yu Chung
- 1 Korea Food Research Institute , Seongnam, Korea
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