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Ma X, Ni J, Wang W, Zhu Y, Zhang Y, Sun M. Protective Effect of Epigallocatechin-3-gallate against Hepatic Oxidative Stress Induced by tert-Butyl Hhydroperoxide in Yellow-Feathered Broilers. Antioxidants (Basel) 2024; 13:1153. [PMID: 39456408 PMCID: PMC11504997 DOI: 10.3390/antiox13101153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 09/13/2024] [Accepted: 09/21/2024] [Indexed: 10/28/2024] Open
Abstract
Recent studies have shown that epigallocatechin-3-gallate (EGCG), as an effective antioxidant, could attenuate the oxidative damage, inflammation and necrosis in the liver in response to oxidative stress. The present study investigated whether oral administration of EGCG could effectively alleviate the hepatic histopathological changes and oxidative damage in yellow-feathered broilers induced by tert-butyl hydroperoxide (t-BHP). Broilers were exposed to 600 μmol t-BHP/kg body weight (BW) to induce oxidative stress by intraperitoneal injection every five days, followed by oral administration of different doses of EGCG (0, 20, 40 and 60 mg/kg BW) and 20 mg vitamin E (VE)/kg BW every day during 5-21 days of age. The results showed that t-BHP injection decreased (p < 0.05) body weight and the relative weight of the spleen; the enzyme activities of total antioxidant capacity (T-AOC), catalase (CAT) and total superoxide dismutase (SOD); and gene mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), CAT, SOD1, SOD2 and acetyl-CoA carboxylase (ACACA); as well as increased (p < 0.05) necrosis formation, malondialdehyde (MDA) content, reactive oxygen species (ROS)accumulation, and peroxisome proliferator activates receptor-α (PPARα) mRNA expression in the liver of yellow-feathered female broilers at 21 days of age. Treatment with 60 mg EGCG/kg BW orally could enhance antioxidant enzyme activities and reverse the hepatic damage induced by t-BHP injection by reducing the accumulation of ROS and MDA in the liver and activating the Nrf2 and PPARα pathways related to the induction of antioxidant gene expression (p < 0.05). In conclusion, intraperitoneal injection of t-BHP impaired body growth and induced hepatic ROS accumulation, which destroyed the antioxidant system and led to oxidative damage in the liver of yellow-feathered broilers from 5 to 21 days of age. It is suggested that EGCG may play an antioxidant role through the Nrf2 and PPARα signaling pathways to effectively protect against t-BHP-induced hepatic oxidative damage in broilers, and the appropriate dose was 60 mg EGCG/kg BW by oral administration.
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Affiliation(s)
- Xinyan Ma
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; (X.M.); (W.W.); (Y.Z.); (Y.Z.)
- Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China
| | - Junli Ni
- Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China;
| | - Wei Wang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; (X.M.); (W.W.); (Y.Z.); (Y.Z.)
| | - Yongwen Zhu
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; (X.M.); (W.W.); (Y.Z.); (Y.Z.)
| | - Yuqing Zhang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; (X.M.); (W.W.); (Y.Z.); (Y.Z.)
| | - Mingfei Sun
- Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China;
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Dong C, Zheng G, Peng J, Guo M, Wu H, Tan Z. Integrative Inducer Intervention and Transcriptomic Analyses Reveal the Metabolism of Paralytic Shellfish Toxins in Azumapecten farreri. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2024; 58:6519-6531. [PMID: 38578272 DOI: 10.1021/acs.est.4c00607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/06/2024]
Abstract
Paralytic shellfish toxins (PSTs) are widely distributed neurotoxins, and the PST metabolic detoxification mechanism in bivalves has received increasing attention. To reveal the effect of phase I (cytochrome P450)-II (GST)-III (ABC transport) metabolic systems on the PST metabolism in Azumapecten farreri, this study amplified stress on the target systems using rifampicin, dl-α-tocopherol, and colchicine; measured PST levels; and conducted transcriptomic analyses. The highest toxin content reached 1623.48 μg STX eq/kg in the hepatopancreas and only 8.8% of that in the gills. Inducer intervention significantly decreased hepatopancreatic PST accumulation. The proportional reductions in the rifampicin-, dl-α-tocopherol-, and colchicine-induced groups were 55.3%, 50.4%, and 36.1%, respectively. Transcriptome analysis showed that 11 modules were significantly correlated with PST metabolism (six positive/five negative), with phase I CYP450 and phase II glutathione metabolism significantly enriched in negatively correlated pathways. Twenty-three phase I-II-III core genes were further validated using qRT-PCR and correlated with PST metabolism, revealing that CYP46A1, CYP4F6, GSTM1, and ABCF2 were significantly correlated, while CYP4F11 and ABCB1 were indirectly correlated. In conclusion, phase I-II-III detoxification enzyme systems jointly participate in the metabolic detoxification of PSTs in A. farreri. This study provides key data support to profoundly elucidate the PST metabolic detoxification mechanism in bivalves.
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Affiliation(s)
- Chenfan Dong
- Key Laboratory of Testing and Evaluation for Aquatic Product Safety and Quality, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China
- College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China
| | - Guanchao Zheng
- Key Laboratory of Testing and Evaluation for Aquatic Product Safety and Quality, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China
| | - Jixing Peng
- Key Laboratory of Testing and Evaluation for Aquatic Product Safety and Quality, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China
| | - Mengmeng Guo
- Key Laboratory of Testing and Evaluation for Aquatic Product Safety and Quality, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China
| | - Haiyan Wu
- Key Laboratory of Testing and Evaluation for Aquatic Product Safety and Quality, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China
| | - Zhijun Tan
- Key Laboratory of Testing and Evaluation for Aquatic Product Safety and Quality, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China
- State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China
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morsi RM, Mansour DS, Mousa AM. Ameliorative potential role of Rosmarinus officinalis extract on toxicity induced by etoposide in male albino rats. BRAZ J BIOL 2024; 84:e258234. [DOI: 10.1590/1519-6984.258234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Accepted: 06/17/2022] [Indexed: 11/21/2022] Open
Abstract
Abstract The present work was showed to assess the effect of administration of rosemary extract on etoposide-induced toxicity, injury and proliferation in male rats were investigated. Forty male albino rats were arranged into four equal groups. 1st group, control; 2nd group, etoposide; 3rd group, co-treated rosemary & etoposide; 4th group, rosemary alone. In comparison to the control group, etoposide administration resulted in a significant increase in serum ALT, AST, ALP, total bilirubin, total protein, and gamma GT. In contrast; a significant decrease in albumin level in etoposide group as compared to G1. G3 revealed a significant decrease in AST, ALT, ALP, total protein and total bilirubin levels and a significant rise in albumin level when compared with G2. Serum levels of urea, creatinine, potassium ions, and chloride ions significantly increased; while sodium ions were significantly decreased in G2 when compared with G1. Also, there was an increase of MDA level for etoposide treated group with corresponding control rats. However, there was a remarkable significant decrease in SOD, GPX and CAT levels in G2 as compared to G1. There was a significant increase in serum hydrogen peroxide (H2O2) and Nitric oxide (NO) levels in group treated with etoposide when compared to control group. It was noticeable that administrated by rosemary alone either with etoposide had not any effect on the levels of H2O2 and Nitric oxide. Serum level of T3 and T4 was significantly increased in etoposide-administered rats in comparison with G1. The administration of rosemary, either alone or with etoposide, increased the serum levels of T3 and T4 significantly when compared to control rats. The gene expression analysis showed significant downregulation of hepatic SOD and GPx in (G2) when compared with (G1). The treatment with rosemary extract produced significant upregulation of the antioxidant enzymes mRNA SOD and GPx. MDA gene was increased in (G2) when contrasted with (G1). Treatment of the etoposide- induced rats with rosemary extract delivered significant decrease in MDA gene expression when compared with etoposide group. Rats treated with etoposide showed significant decline in hepatic Nrf2 protein expression, when compared with G1. While, supplementation of Etoposide- administered rats with the rosemary produced a significant elevation in hepatic Nrf2 protein levels. Additionally, the liver histological structure displayed noticeable degeneration and cellular infiltration in liver cells. It is possible to infer that rosemary has a potential role and that it should be researched as a natural component for etoposide-induced toxicity protection.
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Wang J, Zhang T, Wan C, Lai Z, Li J, Chen L, Li M. The effect of theabrownins on the amino acid composition and antioxidant properties of hen eggs. Poult Sci 2023; 102:102717. [PMID: 37734359 PMCID: PMC10518584 DOI: 10.1016/j.psj.2023.102717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 04/04/2023] [Accepted: 04/09/2023] [Indexed: 09/23/2023] Open
Abstract
Pu-erh tea theabrownins (TBs) exert beneficial effect on egg quality and antioxidant properties of eggs, but the underlying mechanisms behind this response are unclear. In this study, we investigate the effect of TBs on egg antioxidative activity, amino acid and fatty acid profiles, and the underlying relationship between the TBs and oxidant-sensitive Nrf2 signaling pathway in laying hens. Eighty layers were fed a basal diet (control) and 400 mg/kg of TBs supplemented diet for 12 wk. TBs led to an increase in albumen height and Haugh unit (P < 0.05). The albumen lysine, valine, and tryptophan were higher in layers fed TBs, whereas yolk tryptophan, methionine, vitamin A, and α-tocopherol content were enhanced by TBs (P < 0.05). Eggs albumen and yolk showed higher total antioxidant capacity (T-AOC), reducing power (RP), and the scavenging rate of 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH), and lower MDA content than those of eggs from the control group (P < 0.05). Also, magnum Nrf2, hemeoxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), and Bcl2 expression were up-regulated by TBs, whereas magnum proapoptotic gene (Bax, caspase 3, Cyt C) were down-regulated by TBs (P < 0.05). Our findings suggest that TBs improved egg albumen quality and antioxidant activity, and the Nrf2-ARE pathway were found to be involved in this process.
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Affiliation(s)
- Jianping Wang
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, China
| | - Tao Zhang
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, China
| | - Chunpeng Wan
- Research Center of Tea and Tea Culture, College of Agronomy, Jiangxi Agricultural University, Nanchang, 330045, China
| | - Zhangfeng Lai
- Research Center of Tea and Tea Culture, College of Agronomy, Jiangxi Agricultural University, Nanchang, 330045, China
| | - Jun Li
- Tea Science Research Institute, Xiushui, Jiujiang, 332400, China
| | - Luojun Chen
- Tea Science Research Institute, Xiushui, Jiujiang, 332400, China
| | - Mingxi Li
- Research Center of Tea and Tea Culture, College of Agronomy, Jiangxi Agricultural University, Nanchang, 330045, China.
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Peter RM, Chou PJ, Shannar A, Patel K, Pan Y, Dave PD, Xu J, Sarwar MS, Kong ANT. An Update on Potential Molecular Biomarkers of Dietary Phytochemicals Targeting Lung Cancer Interception and Prevention. Pharm Res 2023; 40:2699-2714. [PMID: 37726406 DOI: 10.1007/s11095-023-03595-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 08/23/2023] [Indexed: 09/21/2023]
Abstract
Since ancient times, dietary phytochemicals are known for their medicinal properties. They are broadly classified into polyphenols, terpenoids, alkaloids, phytosterols, and organosulfur compounds. Currently, there is considerable interest in their potential health effects against various diseases, including lung cancer. Lung cancer is the leading cause of cancer deaths with an average of five-year survival rate of lung cancer patients limited to just 14%. Identifying potential early molecular biomarkers of pre-malignant lung cancer cells may provide a strong basis to develop early cancer detection and interception methods. In this review, we will discuss molecular changes, including genetic alterations, inflammation, signal transduction pathways, redox imbalance, epigenetic and proteomic signatures associated with initiation and progression of lung carcinoma. We will also highlight molecular targets of phytochemicals during lung cancer development. These targets mainly consist of cellular signaling pathways, epigenetic regulators and metabolic reprogramming. With growing interest in natural products research, translation of these compounds into new cancer prevention approaches to medical care will be urgently needed. In this context, we will also discuss the overall pharmacokinetic challenges of phytochemicals in translating to humans. Lastly, we will discuss clinical trials of phytochemicals in lung cancer patients.
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Affiliation(s)
- Rebecca Mary Peter
- Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA
| | - Pochung Jordan Chou
- Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA
| | - Ahmad Shannar
- Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA
| | - Komal Patel
- Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA
| | - Yuxin Pan
- Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA
| | - Parv Dushyant Dave
- Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA
| | - Jiawei Xu
- Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA
| | - Md Shahid Sarwar
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA
| | - Ah-Ng Tony Kong
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
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Datta S, Ghosh S, Bishayee A, Sinha D. Flexion of Nrf2 by tea phytochemicals: A review on the chemopreventive and chemotherapeutic implications. Pharmacol Res 2022; 182:106319. [PMID: 35732198 DOI: 10.1016/j.phrs.2022.106319] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 06/16/2022] [Accepted: 06/16/2022] [Indexed: 01/11/2023]
Abstract
Nuclear factor erythroid 2 [NF-E2]-related factor 2 (Nrf2), the redox-sensitive transcription factor, plays a key role in stress-defense and detoxification. Nrf2 is tightly controlled by its negative regulator cum sensor Kelch-[ECH]-associated protein 1 (Keap1). Nrf2 is well known for its dual nature owing to its cancer preventive and cancer promoting abilities. Modulation of this biphasic nature of Nrf2 signaling by phytochemicals may be a potential cancer preventive and anticancer therapeutic strategy. Phytocompounds may either act as Nrf2-activator or Nrf2-inhibitor depending on their differential concentration and varied cellular environment. Tea is not just the most popular global beverage with innumerable health-benefits but has well-established chemopreventive and chemotherapeutic effects. Various types of tea infusions contain a wide range of bioactive compounds, such as polyphenolic catechins and flavonols, which are endowed with potent antioxidant properties. Despite of their rapid biotransformation and poor bioavailability, regular tea consumption is risk-reductive for several cancer forms. Tea catechins show their dual Nrf2-modulatory effect by directly acting on Nrf2-Keap1 or their upstream regulators and downstream effectors in a highly case-specific manner. In this review, we have tried to present a comprehensive evaluation of the Nrf2-mediated chemopreventive and chemotherapeutic applications of tea in various preclinical cancer models, the Nrf2-modulatory mechanisms, and the limitations which need to be addressed in future research.
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Affiliation(s)
- Suchisnigdha Datta
- Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata - 700 026, West Bengal, India
| | - Sukanya Ghosh
- Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata - 700 026, West Bengal, India
| | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA.
| | - Dona Sinha
- Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata - 700 026, West Bengal, India.
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Zhao Y, Chen X, Shen J, Xu A, Wang Y, Meng Q, Xu P. Black Tea Alleviates Particulate Matter-Induced Lung Injury via the Gut-Lung Axis in Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:15362-15373. [PMID: 34904826 DOI: 10.1021/acs.jafc.1c06796] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Black tea, as the most consumed kind of tea, is shown to have beneficial effects on human health. However, its impact on particulate matter (PM) induced lung injury and the mechanisms involved have been sparsely addressed. Here, we show that PM-exposed mice exhibited oxidative stress and inflammation in the lungs, which was significantly alleviated by a daily intake of black tea infusion (TI) in a concentration-dependent manner. Interestingly, both the ethanol-soluble fraction (ES) and the ethanol precipitate fraction (EP) exhibited better effects than those of TI; moreover, EP tended to have stronger protection than ES in some indicators, implying that EP played a dominant role in the prevention effects. Furthermore, fecal microbiota transplantation (FMT) revealed that the gut microbiota was differentially reshaped by TI and its fractions were able to directly alleviate the injury induced by PMs. These results indicate that daily intake of black tea and its fractions, especially EP, may alleviate particulate matter-induced lung injury via the gut-lung axis in mice. In addition, the Lachnospiraceae_NK4A136_group could be the core gut microbe contributing to the protection of EP and thus should be further studied in the future.
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Affiliation(s)
- Yueling Zhao
- Institute of Tea Science, Zhejiang University, Hangzhou 310058, China
| | - Xue Chen
- Institute of Tea Science, Zhejiang University, Hangzhou 310058, China
| | - Jimin Shen
- Institute of Tea Science, Zhejiang University, Hangzhou 310058, China
| | - Anan Xu
- Institute of Tea Science, Zhejiang University, Hangzhou 310058, China
| | - Yuefei Wang
- Institute of Tea Science, Zhejiang University, Hangzhou 310058, China
- Key Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Ministry of Agriculture, Hangzhou 310058, China
| | - Qing Meng
- College of Food Science, Southwest University, Chongqing, 400715, China
| | - Ping Xu
- Institute of Tea Science, Zhejiang University, Hangzhou 310058, China
- Key Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Ministry of Agriculture, Hangzhou 310058, China
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Zhou L, Ding X, Wang J, Bai S, Zeng Q, Su Z, Xuan Y, Zhang K. Tea polyphenols increase the antioxidant status of laying hens fed diets with different levels of ageing corn. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2021; 7:650-660. [PMID: 34401543 PMCID: PMC8342854 DOI: 10.1016/j.aninu.2020.08.013] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 08/10/2020] [Accepted: 08/18/2020] [Indexed: 01/07/2023]
Abstract
This study was conducted to evaluate the effects of ageing corn levels (stored for 4 years) with or without the supplementation of tea polyphenols (TPP) on the performance, egg quality and antioxidant status of laying hens. A total of 288 Lohmann commercial laying hens (63-week-old) were used under a 2 × 4 factorial arrangement with 4 levels of dietary ageing corn (0%, 25%, 50%, or 100%) and 2 levels of TPP (0 and 600 mg/kg) for 8 wk. Dietary ageing corn linearly decreased (P < 0.05) the egg production, serum total antioxidant capacity (T-AOC), liver glutathione peroxidase (GSH-Px) of laying hens, yolk index, yolk colour, 1,1-diphenyl-2-picrylhydrazyl (DPPH) value and the reducing power value of egg yolk, but it linearly increased (P < 0.05) the feed conversion rate, ovary malondialdehyde (MDA) content of laying hens, and the protein carbonyl content of egg yolk. Tea polyphenol supplementation increased (P < 0.05) the serum T-AOC, serum superoxide dismutase (SOD), liver SOD, liver GSH-Px, ovary SOD, GSH-Px, the expression of antioxidant-related genes of laying hens, albumen height, Haugh unit, DPPH value and the majority free amino acids of egg yolk, but it decreased (P < 0.05) the serum MDA content of laying hens, MDA and protein carbonyl of egg yolk. In conclusion, the ageing corn significantly reduced the performance, egg quality, antioxidant status and egg antioxidant capacity of laying hens, while TPP supplementation partially counteracted the adverse effects, especially antioxidant status and egg antioxidant capacity of laying hens.
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Affiliation(s)
- Ling Zhou
- Institute of Animal Nutrition, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, 211 Huimin Road, Wenjiang, Chengdu, 611130, China
| | - Xuemei Ding
- Institute of Animal Nutrition, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, 211 Huimin Road, Wenjiang, Chengdu, 611130, China
| | - Jianping Wang
- Institute of Animal Nutrition, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, 211 Huimin Road, Wenjiang, Chengdu, 611130, China
| | - Shiping Bai
- Institute of Animal Nutrition, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, 211 Huimin Road, Wenjiang, Chengdu, 611130, China
| | - Qiufeng Zeng
- Institute of Animal Nutrition, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, 211 Huimin Road, Wenjiang, Chengdu, 611130, China
| | - Zuowei Su
- Institute of Animal Nutrition, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, 211 Huimin Road, Wenjiang, Chengdu, 611130, China
| | - Yue Xuan
- Institute of Animal Nutrition, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, 211 Huimin Road, Wenjiang, Chengdu, 611130, China
| | - Keying Zhang
- Institute of Animal Nutrition, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, 211 Huimin Road, Wenjiang, Chengdu, 611130, China
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Role of Herbal Teas in Regulating Cellular Homeostasis and Autophagy and Their Implications in Regulating Overall Health. Nutrients 2021; 13:nu13072162. [PMID: 34201882 PMCID: PMC8308238 DOI: 10.3390/nu13072162] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 06/19/2021] [Accepted: 06/20/2021] [Indexed: 02/06/2023] Open
Abstract
Tea is one of the most popular and widely consumed beverages worldwide, and possesses numerous potential health benefits. Herbal teas are well-known to contain an abundance of polyphenol antioxidants and other ingredients, thereby implicating protection and treatment against various ailments, and maintaining overall health in humans, although their mechanisms of action have not yet been fully identified. Autophagy is a conserved mechanism present in organisms that maintains basal cellular homeostasis and is essential in mediating the pathogenesis of several diseases, including cancer, type II diabetes, obesity, and Alzheimer’s disease. The increasing prevalence of these diseases, which could be attributed to the imbalance in the level of autophagy, presents a considerable challenge in the healthcare industry. Natural medicine stands as an effective, safe, and economical alternative in balancing autophagy and maintaining homeostasis. Tea is a part of the diet for many people, and it could mediate autophagy as well. Here, we aim to provide an updated overview of popular herbal teas’ health-promoting and disease healing properties and in-depth information on their relation to autophagy and its related signaling molecules. The present review sheds more light on the significance of herbal teas in regulating autophagy, thereby improving overall health.
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Jideani AIO, Silungwe H, Takalani T, Omolola AO, Udeh HO, Anyasi TA. Antioxidant-rich natural fruit and vegetable products and human health. INTERNATIONAL JOURNAL OF FOOD PROPERTIES 2021. [DOI: 10.1080/10942912.2020.1866597] [Citation(s) in RCA: 97] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Afam I. O. Jideani
- Department of Food Science and Technology, School of Agriculture, University of Venda, Thohoyandou 0950, South Africa
- Postharvest-Handling Group, ISEKI-Food Association, Vienna, Austria
| | - Henry Silungwe
- Department of Food Science and Technology, School of Agriculture, University of Venda, Thohoyandou 0950, South Africa
| | - Thakhani Takalani
- Univen Centre for Continuing Education, University of Venda, Thohoyandou 0950, South Africa
| | - Adewale O Omolola
- Department of Agricultural Engineering, School of Agriculture, University of Venda, Thohoyandou 0950, South Africa
| | - Henry O Udeh
- Department of Food Science and Technology, School of Agriculture, University of Venda, Thohoyandou 0950, South Africa
| | - Tonna A Anyasi
- Department of Food Science and Technology, Cape Peninsula University of Technology, Bellville 7535, South Africa
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Yan Z, Zhong Y, Duan Y, Chen Q, Li F. Antioxidant mechanism of tea polyphenols and its impact on health benefits. ACTA ACUST UNITED AC 2020; 6:115-123. [PMID: 32542190 PMCID: PMC7283370 DOI: 10.1016/j.aninu.2020.01.001] [Citation(s) in RCA: 328] [Impact Index Per Article: 65.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 01/08/2020] [Accepted: 01/09/2020] [Indexed: 12/18/2022]
Abstract
Tea trees have a long history of cultivation and utilization. People in many countries have the habit of drinking tea and choosing green tea, oolong tea, or black tea according to different regions and personal tastes. Tea polyphenols are a general term for polyphenol compounds in tea, and has been shown to have good effects on antioxidant, anti-inflammatory, cancer prevention and regulation of lipid metabolism. Tea polyphenols have been widely used as antioxidants in disease treatment and animal husbandry, but their specific mechanism of action needs to be further clarified and revealed. This review focuses on the definition, classification, antioxidant activity and the regulation of signaling pathways of tea polyphenols. This paper also aims to examine the application of tea polyphenols in human and animal health, providing a scientific basis for this application in addition to proposing future directions for the development of this resource.
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Affiliation(s)
- Zhaoming Yan
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China.,Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture Chinese Academy of Sciences, Key Laboratory of Agro-ecological Processes in Subtropical Region, Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha 410125, China
| | - Yinzhao Zhong
- College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Yehui Duan
- Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture Chinese Academy of Sciences, Key Laboratory of Agro-ecological Processes in Subtropical Region, Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha 410125, China
| | - Qinghua Chen
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Fengna Li
- Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture Chinese Academy of Sciences, Key Laboratory of Agro-ecological Processes in Subtropical Region, Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha 410125, China.,Hunan Co-Innovation Center of Animal Production Safety, Hunan Collaborative Innovation Center for Utilization of Botanical Functional Ingredients, Changsha 410128, China
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12
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Zeng Z, Wang ZY, Li YK, Ye DM, Zeng J, Hu JL, Chen PF, Xiao J, Zou J, Li ZH. Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) in non-small cell lung cancer. Life Sci 2020; 254:117325. [PMID: 31954159 DOI: 10.1016/j.lfs.2020.117325] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 01/10/2020] [Accepted: 01/13/2020] [Indexed: 12/15/2022]
Abstract
Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is a transcription factor that can regulate downstream target gene expression. Kelch-like ECH-associated protein 1 (Keap1) negatively regulates Nrf2 activation and translocation to target its 26S proteasomal degradation. It has been widely reported that the Keap1/Nrf2 pathway is associated with tumorigenesis, chemotherapy resistance and progression and development of non-small cell lung cancer (NSCLC). High expression of Nrf2 and low abundance of Keap1 contribute to the abnormalities and unrealistic treatment prognosis of NSCLC. Therefore, elucidating the role and potential mechanism of Nrf2 in NSCLC is essential for understanding tumorigenesis and for the development of strategies for effective clinical management. Here, we summarize current knowledge about the molecular structure and biological function of Nrf2, and we discuss the roles of Nrf2 in tumorigenesis, which will further provide a possible therapeutic strategy for NSCLC.
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Affiliation(s)
- Zhi Zeng
- Department of Pathology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning 437000, PR China
| | - Zi-Yao Wang
- Ultrasound B Imaging Division, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, PR China
| | - Yu-Kun Li
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, University of South China, Hengyang, Hunan 421001, PR China
| | - Dong-Mei Ye
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, University of South China, Hengyang, Hunan 421001, PR China
| | - Juan Zeng
- Department of Anesthesiology, The Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, PR China
| | - Jia-Li Hu
- Department of Pathology, Jiujiang University Clinic College Hospital, Jiujiang, Jiangxi 332000, PR China
| | - Pi-Feng Chen
- Department of Pediatric Surgery, Jiujiang Maternal and Child Health Hospital, Jiujiang, Jiangxi 332000, PR China
| | - Jiao Xiao
- Department of Endocrinology, The Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421002, PR China
| | - Juan Zou
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, University of South China, Hengyang, Hunan 421001, PR China.
| | - Zhen-Hua Li
- Department of Cardiothoracic Surgery, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning 437000, PR China.
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13
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Abdul Rahim R, Jayusman PA, Muhammad N, Ahmad F, Mokhtar N, Naina Mohamed I, Mohamed N, Shuid AN. Recent Advances in Nanoencapsulation Systems Using PLGA of Bioactive Phenolics for Protection against Chronic Diseases. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:E4962. [PMID: 31817699 PMCID: PMC6950714 DOI: 10.3390/ijerph16244962] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 12/03/2019] [Accepted: 12/04/2019] [Indexed: 12/12/2022]
Abstract
Plant-derived polyphenolic compounds have gained widespread recognition as remarkable nutraceuticals for the prevention and treatment of various disorders, such as cardiovascular, neurodegenerative, diabetes, osteoporosis, and neoplastic diseases. Evidence from the epidemiological studies has suggested the association between long-term consumption of diets rich in polyphenols and protection against chronic diseases. Nevertheless, the applications of these phytochemicals are limited due to its low solubility, low bioavailability, instability, and degradability by in vivo and in vitro conditions. Therefore, in recent years, newer approaches have been attempted to solve the restrictions related to their delivery system. Nanoencapsulation of phenolic compounds with biopolymeric nanoparticles could be a promising strategy for protection and effective delivery of phenolics. Poly(lactic-co-glycolic acid) (PLGA) is one of the most successfully developed biodegradable polymers that has attracted considerable attention due to its attractive properties. In this review, our main goal is to cover the relevant recent studies that explore the pharmaceutical significance and therapeutic superiority of the advance delivery systems of phenolic compounds using PLGA-based nanoparticles. A summary of the recent studies implementing encapsulation techniques applied to polyphenolic compounds from plants confirmed that nanoencapsulation with PLGA nanoparticles is a promising approach to potentialize their therapeutic activity.
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Affiliation(s)
- Rohanizah Abdul Rahim
- Pharmacology Department, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, 56000 Kuala Lumpur, Malaysia; (R.A.R.); (P.A.J.); (N.M.); (I.N.M.)
- Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200 Kepala Batas, Pulau Pinang, Malaysia
| | - Putri Ayu Jayusman
- Pharmacology Department, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, 56000 Kuala Lumpur, Malaysia; (R.A.R.); (P.A.J.); (N.M.); (I.N.M.)
| | - Norliza Muhammad
- Pharmacology Department, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, 56000 Kuala Lumpur, Malaysia; (R.A.R.); (P.A.J.); (N.M.); (I.N.M.)
| | - Fairus Ahmad
- Anatomy Department, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, 56000 Kuala Lumpur, Malaysia;
| | - Norfilza Mokhtar
- Physiology Department, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, 56000 Kuala Lumpur, Malaysia;
| | - Isa Naina Mohamed
- Pharmacology Department, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, 56000 Kuala Lumpur, Malaysia; (R.A.R.); (P.A.J.); (N.M.); (I.N.M.)
| | - Norazlina Mohamed
- Pharmacology Department, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, 56000 Kuala Lumpur, Malaysia; (R.A.R.); (P.A.J.); (N.M.); (I.N.M.)
| | - Ahmad Nazrun Shuid
- Pharmacology Department, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, 56000 Kuala Lumpur, Malaysia; (R.A.R.); (P.A.J.); (N.M.); (I.N.M.)
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Mao X, Xiao X, Chen D, Yu B, He J. Tea and Its Components Prevent Cancer: A Review of the Redox-Related Mechanism. Int J Mol Sci 2019; 20:E5249. [PMID: 31652732 PMCID: PMC6862630 DOI: 10.3390/ijms20215249] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Revised: 10/21/2019] [Accepted: 10/21/2019] [Indexed: 02/07/2023] Open
Abstract
Cancer is a worldwide epidemic and represents a major threat to human health and survival. Reactive oxygen species (ROS) play a dual role in cancer cells, which includes both promoting and inhibiting carcinogenesis. Tea remains one of the most prevalent beverages consumed due in part to its anti- or pro-oxidative properties. The active compounds in tea, particularly tea polyphenols, can directly or indirectly scavenge ROS to reduce oncogenesis and cancerometastasis. Interestingly, the excessive levels of ROS induced by consuming tea could induce programmed cell death (PCD) or non-PCD of cancer cells. On the basis of illustrating the relationship between ROS and cancer, the current review discusses the composition and efficacy of tea including the redox-relative (including anti-oxidative and pro-oxidative activity) mechanisms and their role along with other components in preventing and treating cancer. This information will highlight the basis for the clinical utilization of tea extracts in the prevention or treatment of cancer in the future.
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Affiliation(s)
- Xiangbing Mao
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China.
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Chengdu 611130, China.
- Key Laboratory of Animal Disease-Resistance Nutrition and Feed, Ministry of Agriculture and Rural Affairs, Chengdu 611130, China.
- Key Laboratory of Animal Disease-Resistance Nutrition, Chengdu 611130, China.
| | - Xiangjun Xiao
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China.
| | - Daiwen Chen
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China.
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Chengdu 611130, China.
- Key Laboratory of Animal Disease-Resistance Nutrition and Feed, Ministry of Agriculture and Rural Affairs, Chengdu 611130, China.
- Key Laboratory of Animal Disease-Resistance Nutrition, Chengdu 611130, China.
| | - Bing Yu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China.
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Chengdu 611130, China.
- Key Laboratory of Animal Disease-Resistance Nutrition and Feed, Ministry of Agriculture and Rural Affairs, Chengdu 611130, China.
- Key Laboratory of Animal Disease-Resistance Nutrition, Chengdu 611130, China.
| | - Jun He
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China.
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Chengdu 611130, China.
- Key Laboratory of Animal Disease-Resistance Nutrition and Feed, Ministry of Agriculture and Rural Affairs, Chengdu 611130, China.
- Key Laboratory of Animal Disease-Resistance Nutrition, Chengdu 611130, China.
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15
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Rice Bran Phenolic Compounds Regulate Genes Associated with Antioxidant and Anti-Inflammatory Activity in Human Umbilical Vein Endothelial Cells with Induced Oxidative Stress. Int J Mol Sci 2019; 20:ijms20194715. [PMID: 31547608 PMCID: PMC6801753 DOI: 10.3390/ijms20194715] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Revised: 09/16/2019] [Accepted: 09/20/2019] [Indexed: 12/18/2022] Open
Abstract
Oxidative stress, inflammation and endothelial dysfunction are associated with the development of cardiovascular and metabolic diseases. Phenolic extracts derived from rice bran (RB) are recognised to have antioxidant and anti-inflammatory potential. However, the underlying mechanisms remain unknown. Therefore, this study aimed to evaluate the ability of RB-derived phenolic extracts to modulate genes associated with antioxidant and anti-inflammatory pathways in human umbilical vein endothelial cells (HUVECs) under induced oxidative stress conditions. HUVECs under oxidative stress were treated with varying concentrations of RB phenolic extracts (25–250 µg/mL). Using quantitative real-time polymerase chain reaction, the expression of candidate genes that regulate antioxidant and anti-inflammatory pathways were determined. This included nuclear factor erythroid 2-related factor 2 (Nrf2), nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO1), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), intercellular adhesion molecule 1 (ICAM1), endothelial nitric oxide synthase (eNOS), ectonucleoside triphosphate diphosphohydrolase 1 (CD39) and ecto-5′-nucleotidase (CD73). Phenolic extracts derived from RB down-regulated the expression of four genes, ICAM1, CD39, CD73 and NOX4 and up-regulated the expression of another four genes, Nrf2, NQO1, HO1 and eNOS, indicating an antioxidant/ anti-inflammatory effect for RB against endothelial dysfunction.
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16
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Xue Y, Du M, Zhu MJ. Raspberry extract prevents NLRP3 inflammasome activation in gut epithelial cells induced by pathogenic Escherichia coli. J Funct Foods 2019. [DOI: 10.1016/j.jff.2019.03.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
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17
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Hudlikar RR, Pai V, Kumar R, Thorat RA, Kannan S, Ingle AD, Maru GB, Mahimkar MB. Dose-Related Modulatory Effects of Polymeric Black Tea Polyphenols (PBPs) on Initiation and Promotion Events in B(a)P and NNK-Induced Lung Carcinogenesis. Nutr Cancer 2019; 71:508-523. [PMID: 30857437 DOI: 10.1080/01635581.2019.1578389] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Our understanding of dose-related effects of polymeric black tea polyphenols (PBPs), the most abundant polyphenols in black tea, is limited. In the present study, the effect of various doses of black tea (0.75, 1.5, and 3%)-derived PBP-rich extract on biochemical parameters and lung carcinogenicity in A/J mice was investigated. Pretreatment with PBPs showed the dose-related decrease in B(a)P-induced expression and activity of CYP1A1 in the liver while CYP1A2 expression and activity in the lung. Dose-dependent significant increase in PBP-mediated over-expression and activity of GSTs (alpha in the liver while pi in the lung) were observed in polyphenol-treated groups. Significant dose-related decrease in number and intensity of BPDE-DNA adducts were observed in liver and lung. Black tea (1.5%, 3%)-derived PBPs showed dose-mediated decrease in lung tumor incidence and multiplicity which was further correlated with different molecular markers like cell proliferation and apoptosis in B(a)P and NNK model. In conclusion, dose-dependent chemopreventive effects of PBPs, both anti-initiating (induction of phase II and inhibition of carcinogen-induced phase-I enzymes leading to decrease in BPDE-DNA adducts) and anti-promoting (decreased cell proliferation and increased apoptosis lowering incidence and/or multiplicity of lung lesions), were observed in A/J mice without significant toxicity.
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Affiliation(s)
- Rasika R Hudlikar
- a Cancer Research Institute, Advanced Centre for Treatment , Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC) , Kharghar , Navi Mumbai , India.,b Homi Bhabha National Institute , Training School Complex , Anushakti Nagar , Mumbai , India
| | - Venkatesh Pai
- a Cancer Research Institute, Advanced Centre for Treatment , Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC) , Kharghar , Navi Mumbai , India
| | - Rajiv Kumar
- c Department of Pathology , Tata Memorial Hospital, Tata Memorial Centre (TMC) , Parel , Mumbai , India
| | - Rahul A Thorat
- b Homi Bhabha National Institute , Training School Complex , Anushakti Nagar , Mumbai , India.,d Laboratory Animal Facility, Advanced Centre for Treatment , Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC) , Kharghar , Navi Mumbai , India
| | - Sadhana Kannan
- e Epidemiology and Clinical Trial Unit (ECTU) , Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC) , Kharghar , Navi Mumbai , India
| | - Arvind D Ingle
- b Homi Bhabha National Institute , Training School Complex , Anushakti Nagar , Mumbai , India.,d Laboratory Animal Facility, Advanced Centre for Treatment , Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC) , Kharghar , Navi Mumbai , India
| | - Girish B Maru
- a Cancer Research Institute, Advanced Centre for Treatment , Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC) , Kharghar , Navi Mumbai , India
| | - Manoj B Mahimkar
- a Cancer Research Institute, Advanced Centre for Treatment , Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC) , Kharghar , Navi Mumbai , India.,b Homi Bhabha National Institute , Training School Complex , Anushakti Nagar , Mumbai , India
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Imran A, Butt MS, Xiao H, Imran M, Rauf A, Mubarak MS, Ramadan MF. Inhibitory effect of black tea (Camellia sinensis) theaflavins and thearubigins against HCT 116 colon cancer cells and HT 460 lung cancer cells. J Food Biochem 2019; 43:e12822. [PMID: 31353529 DOI: 10.1111/jfbc.12822] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Revised: 02/11/2019] [Accepted: 02/14/2019] [Indexed: 12/01/2022]
Abstract
Recently, phytochemical-based dietary intervention has gained attention as a preventive and curative strategy against cancers owing to their safety, better tolerance, and economics. Against this background, black tea extract which contains the flavanol-3-ol, theaflavins (TF), and thearubigins (TR) with promising anti-oncogenic activity were assessed to determine its in vitro inhibitory impact on colon cancer (HCT 116) and lung cancer cell lines (HT 460). In a dose-dependent manner, results revealed that TF, TR, and their combinations cause inhibition in cell viability. However, TF imparted a maximum reduction in cell viability of HCT 116 and HT 460. Flow cytometry data revealed that TF, TR, and their combinations exhibited substantial cell arrest at the G2/M phase. The influence was more prominent in lung cancer cells (HT 460) when compared with colon cells (HCT 116). All treatments resulted in apoptosis, however, the combination of TF and TR exhibited the highest apoptotic ability in comparison to individual treatments. TF and TR exhibited a synergistic impact and significantly inhibited cell proliferation of HCT 116 and HT 460 in dose- and time-dependent manners by inducing apoptosis and cell cycle arrest, wherein TF showed a more pronounced impact. PRACTICAL APPLICATIONS: Results from the present study revealed that black tea-isolated polyphenols (TF and TR) exhibited a significant inhibition of lung and colon cancer cell growth. A promising synergistic effect of TF and TR as inhibitors of cancer cells was observed. More clinical work, perhaps on a human subject, is needed before these two isolated compounds can be prescribed as anticancer drugs.
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Affiliation(s)
- Ali Imran
- Institute of Home and Food Sciences, Government College University, Faisalabad, Pakistan
| | - Masood Sadiq Butt
- National Institute of Food Science and Technology, University of Agriculture Faisalabad, Faisalabad, Pakistan
| | - Hang Xiao
- Department of Food Science, University of Massachusetts, Amherst, Massachusetts
| | - Muhammad Imran
- Department of Diet and Nutritional Sciences, Imperial College of Business Studies, Lahore, Pakistan.,Faculty of Allied Health Sciences, University Institute of Diet and Nutritional Sciences, The University of Lahore, Lahore, Pakistan
| | - Abdur Rauf
- Department of Chemistry, Univesity of Swabi, Khyber Pakhtunkhwa, Pakistan
| | | | - Mohamed Fawzy Ramadan
- Faculty of Agriculture, Department of Biochemistry, Zagazig University, Zagazig, Egypt
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Liu X, Huang K, Niu Z, Mei D, Zhang B. Protective effect of isochlorogenic acid B on liver fibrosis in non-alcoholic steatohepatitis of mice. Basic Clin Pharmacol Toxicol 2018; 124:144-153. [PMID: 30180301 DOI: 10.1111/bcpt.13122] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Accepted: 08/25/2018] [Indexed: 02/06/2023]
Abstract
Liver fibrosis is a common symptom of non-alcoholic steatohepatitis (NASH) and a worldwide clinical issue. The miR-122/HIF-1α signalling pathway is believed to play an important role in the genesis of progressive fibrosis. Isochlorogenic acid B (ICAB), naturally isolated from Laggera alata, is verified to have antioxidative and hepatoprotective properties. The aim of this study was to investigate the effect of ICAB on liver fibrosis in NASH and its potential protective mechanisms. NASH was induced in a mouse model with a methionine- and choline-deficient (MCD) diet for 4 weeks, and ICAB was orally administered every day at three doses (5, 10 and 20 mg/kg). Pathological results indicated that ICAB significantly improved the pathological lesions of liver fibrosis. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic hydroxyproline (Hyp), cholesterol (CHO) and triglyceride (TG) were also significantly decreased by ICAB. In addition, ICAB inhibited hepatic stellate cells (HSCs) activation and the expressions of hepatic genes involved in liver fibrosis including LOX, TGF-β1, MCP-1, COL1α1 and TIMP-1. ICAB also attenuated liver oxidative stress through Nrf2 signalling pathway. What is more, the decreased levels of miR-122 and over-expression of hepatic HIF-1α could be reversed by ICAB treatment. These results simultaneously confirmed that ICAB had a significant protective effect on fibrosis in NASH by inhibiting oxidative stress via Nrf2 and suppressing multiple profibrogenic factors through miR-122/HIF-1α signalling pathway.
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Affiliation(s)
- Xin Liu
- Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Kai Huang
- Drug Clinical Trial Institution, Wuxi People' Hospital, Nanjing Medical University, Wuxi, China
| | - Ziran Niu
- Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dan Mei
- Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bo Zhang
- Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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20
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Imran A, Arshad MU, Arshad MS, Imran M, Saeed F, Sohaib M. Lipid peroxidation diminishing perspective of isolated theaflavins and thearubigins from black tea in arginine induced renal malfunctional rats. Lipids Health Dis 2018; 17:157. [PMID: 30021615 PMCID: PMC6052712 DOI: 10.1186/s12944-018-0808-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Accepted: 06/28/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Recently oxidative stress induced maladies have amplified owing to sedentary lifestyle and monotonous diet. Introduction of plant based biomolecules may be a suitable strategy to cope with the lipid peroxidation. In this context, black tea polyphenols (theaflavin & thearubigins) are in fame among the scientific community as cost effective therapeutic agents owing to their safety, economics, structural diversity and ability to modulate various lipid peroxidation responses by halting the expression of different metabolic targets. METHODS The mandate of present investigation was to first time check the synergism among the isolated theaflavins & thearubigins against lipid peroxidative indicators both in vitro and in vivo. Purposely, theaflavins and thearubigins were isolated from black tea through solvent partition methods by using different solvents (Aqueous ethanol, Aqueous methanol & Water) and time intervals (30, 60 & 90 min) and subjected to in vitro characterization through different antioxidant indices to access the in vitro lipid peroxidation shooting effect of these bioactive moieties. Moreover, individual theaflavins contents also estimate through HPLC. For evaluation of in vivo antioxidant effect, renal malfunction was induced through arginine and forty rats were divided in four groups (10 each after power analysis) and 04 types of diets were given i.e. T0 (control diet without supplementation), T1 (Basic experimental Diet+ theaflavins supplementation @ 1 g), T2 (Basic experimental Diet+ Thearubigins supplementation @ 1 g) & T3 (Basic experimental Diet+ Supplementation of theaflavins+ thearubigins @ 0.5 + 0.5 g, respectively) for the period of 56 days. Alongside, a control study was also carried out for comparison by involving normal rats fed on arginine free diet. The body weight, lipid profile, glycemic responses, Renal function test, liver function test, antioxidant indices and hematological parameters were estimated at the termination of study. RESULTS The results indicated that theaflavins and thearubigins isolation was significantly affected by time of extraction and solvent. In this context, aqueous ethanol at 60 min extraction interval caused maximum extraction. Likewise, theaflavins isolate exhibited more antioxidant activity as compared to thearubigins. Moreover, the theaflavins and thearubigins based experimental diets imparted significant reduction in Lipid profile, glucose content, renal function tests and TBARS with enhancement in insulin, HDL and hematological parameters. In this context, theaflavin based diet caused maximum reduction in lipid profile and TBARS better as compared to thearubigins and theaflavins + thearubigins based. However, theaflavin+ thearubigins based diet caused highest glucose, urea & creatinine decline and maximum insulin increase & antioxidant indices as compared to other nutraceuticals. CONCLUSIONS It was deduced that theaflavins & thearubigins have strong antioxidative potential both in in vitro as well as in vivo to tackle the menace associated with lipid peroxidation.
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Affiliation(s)
- Ali Imran
- Institute of Home and Food Sciences, Government College University, Faisalabad, 38040 Pakistan
| | - Muhammad Umair Arshad
- Institute of Home and Food Sciences, Government College University, Faisalabad, 38040 Pakistan
| | - Muhammad Sajid Arshad
- Institute of Home and Food Sciences, Government College University, Faisalabad, 38040 Pakistan
| | - Muhammad Imran
- University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, The University Of Lahore-Pakistan, Lahore, Pakistan
| | - Farhan Saeed
- Institute of Home and Food Sciences, Government College University, Faisalabad, 38040 Pakistan
| | - Muhammad Sohaib
- Department of Food Science and Human Nutrition, University of Veterinary and Animal Sciences, Lahore, 54000 Pakistan
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21
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An in vitro comparative study of the antioxidant activity and SIRT1 modulation of natural compounds. Biomed Pharmacother 2018. [PMID: 29525677 DOI: 10.1016/j.biopha.2018.03.006] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Oxidative stress arises from an imbalance between the production of free radicals and antioxidant defences. Several studies have suggested that dietary antioxidants (such as polyphenols and berberine) may counteract oxidative stress through the involvement of the Sirtuin 1/Adenosine Monophosphate-Activated Protein Kinase (SIRT1/AMPK) pathway. The aim of this study was to evaluate the direct and specific antioxidant activity of some natural compounds, as well as their ability to modulate the expression of SIRT1 and the activation of AMPK. Quercetin, tyrosol, ferulic acid, catechin, berberine and curcumin were evaluated for their specific and direct antioxidant activity with TOSC assay. Their ability to modulate SIRT1 and AMPK was assessed by immunoblotting assay, while their cytotoxicity by CellTiter-Blue Cell Viability Assay. No statistically significant decrease (p > 0.05) in the number of viable cells was found upon challenging with the natural compounds. Quercetin exhibited the highest antioxidant activity against peroxyl radical and peroxinitrate derivates, while curcumin showed the best anti-hydroxyl activity with respect to the other compounds and, most importantly, respect to the reference antioxidants. Finally, all the tested compounds significantly increased the SIRT1 expression and the activation of AMPK. Our results clearly disclose the specific antioxidant activity of these natural compounds and their ability to increase SIRT1 expression and AMPK activation.
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Multi-targeted protection of acetaminophen-induced hepatotoxicity in mice by tannic acid. Int Immunopharmacol 2017; 47:95-105. [PMID: 28376392 DOI: 10.1016/j.intimp.2017.03.027] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2016] [Revised: 03/23/2017] [Accepted: 03/28/2017] [Indexed: 01/14/2023]
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Zou L, Chen S, Li L, Wu T. The protective effect of hyperoside on carbon tetrachloride-induced chronic liver fibrosis in mice via upregulation of Nrf2. ACTA ACUST UNITED AC 2017; 69:451-460. [PMID: 28434817 DOI: 10.1016/j.etp.2017.04.001] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Revised: 03/15/2017] [Accepted: 04/03/2017] [Indexed: 01/12/2023]
Abstract
CONTEXT Hyperoside was used to treat cardiovascular disease for many years in China. It was shown great effect on regulation of lipid metabolism. But there is lack of reports about the effects of hyperoside on liver diseases. OBJECTIVE This study was designed to investigate the potentially protective effects of hyperoside and the role of transcription factor nuclear factor-erythroid 2(NF-E2)-related factor 2 (Nrf2) signaling in the regulation on Carbon Tetrachloride (CCl4)-induced chronic liver fibrosis in mice. MATERIALS AND METHODS All mice were divided into six groups containing 6 animals per group. Mice in different group were given relative processing for 4 weeks. The potentially protective effects of hyperoside on CCl4-induced chronic liver fibrosis in mice were depicted histologically and biochemically. RESULTS CCl4 administration caused a marked increase in the levels of serum aminotransferases, serum monoamine oxidase (MAO) and lipid peroxidation, MAO in mouse liver homogenates. Also decreased activities of cellular antioxidant defense enzymes were found after CCl4 exposure. Histopathological changes induced by CCl4 including regenerative nodules, deteriorated parenchyma. Hyperoside and silymarin reduced these changes and attenuated the pathological effects of CCl4 induced liver injury. In addition, hyperoside exhibited antioxidant effects in vitro. In Western blot analysis, the protein level of Nrf2 was downregulated after CCl4 administration and reversed by hyperoside. CONCLUSION Hyperoside increased the activity of the antioxidant and phase II detoxifying enzymes through the activation of Nrf2 nuclear translocated in the CCl4-induced liver fibrosis mice.
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Affiliation(s)
- Liyi Zou
- School of Pharmacy, Guangdong Medical University, Dongguan 523-808, China
| | - Shaoru Chen
- State key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
| | - Li Li
- Dongguan Scientific Research Center, Guangong Medical University, Dongguan, Guangdong, 523-808, China.
| | - Tie Wu
- School of Pharmacy, Guangdong Medical University, Dongguan 523-808, China.
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Dasilva G, Pazos M, García-Egido E, Gallardo JM, Ramos-Romero S, Torres JL, Romeu M, Nogués MR, Medina I. A lipidomic study on the regulation of inflammation and oxidative stress targeted by marine ω-3 PUFA and polyphenols in high-fat high-sucrose diets. J Nutr Biochem 2017; 43:53-67. [PMID: 28260647 DOI: 10.1016/j.jnutbio.2017.02.007] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Revised: 01/19/2017] [Accepted: 02/08/2017] [Indexed: 01/14/2023]
Abstract
The ability of polyphenols to ameliorate potential oxidative damage of ω-3 PUFAs when they are consumed together and then, to enhance their potentially individual effects on metabolic health is discussed through the modulation of fatty acids profiling and the production of lipid mediators. For that, the effects of the combined consumption of fish oils and grape seed procyanidins on the inflammatory response and redox unbalance triggered by high-fat high-sucrose (HFHS) diets were studied in an animal model of Wistar rats. A standard diet was used as control. Results suggested that fish oils produced a replacement of ω-6 by ω-3 PUFAs in membranes and tissues, and consequently they improved inflammatory and oxidative stress parameters: favored the activity of 12/15-lipoxygenases on ω-3 PUFAs, enhanced glutathione peroxidases activity, modulated proinflammatory lipid mediators synthesis through the cyclooxygenase (COX) pathways and down-regulated the synthesis de novo of ARA leaded by Δ5 desaturase. Although polyphenols exerted an antioxidative and antiinflammatory effect in the standard diet, they were less effective to reduce inflammation in the HFHS dietary model. Contrary to the effect observed in the standard diet, polyphenols up-regulated COX pathways toward ω-6 proinflammatory eicosanoids as PGE2 and 11-HETE and decreased the detoxification of ω-3 hydroperoxides in the HFHS diet. As a result, additive effects between fish oils and polyphenols were found in the standard diet in terms of reducing inflammation and oxidative stress. However, in the HFHS diets, fish oils seem to be the one responsible for the positive effects found in the combined group.
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Affiliation(s)
- Gabriel Dasilva
- Instituto de Investigaciones Marinas, Consejo Superior de Investigaciones Científicas (IIM-CSIC), E-36208 Vigo, Galicia, Spain; Department of Analytical Chemistry, Nutrition and Bromatology and Research Institute for Food Analysis (I.I.A.A.), University of Santiago de Compostela, E-15782 Santiago de Compostela, Galicia, Spain.
| | - Manuel Pazos
- Instituto de Investigaciones Marinas, Consejo Superior de Investigaciones Científicas (IIM-CSIC), E-36208 Vigo, Galicia, Spain
| | - Eduardo García-Egido
- Instituto de Investigaciones Marinas, Consejo Superior de Investigaciones Científicas (IIM-CSIC), E-36208 Vigo, Galicia, Spain
| | - José M Gallardo
- Instituto de Investigaciones Marinas, Consejo Superior de Investigaciones Científicas (IIM-CSIC), E-36208 Vigo, Galicia, Spain
| | - Sara Ramos-Romero
- Instituto de Química Avanzada de Catalunya (IQAC-CSIC), Jordi Girona 18-26, E-08034 Barcelona, Spain
| | - Josep Lluís Torres
- Instituto de Química Avanzada de Catalunya (IQAC-CSIC), Jordi Girona 18-26, E-08034 Barcelona, Spain
| | - Marta Romeu
- Unidad de Farmacología, Facultad de Medicina, Universidad Rovira i Virgili, Sant Llorenç 21, E-43201 Reus, Spain
| | - María-Rosa Nogués
- Unidad de Farmacología, Facultad de Medicina, Universidad Rovira i Virgili, Sant Llorenç 21, E-43201 Reus, Spain
| | - Isabel Medina
- Instituto de Investigaciones Marinas, Consejo Superior de Investigaciones Científicas (IIM-CSIC), E-36208 Vigo, Galicia, Spain
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Li S, Li X, Shpigelman A, Lorenzo JM, Montesano D, Barba FJ. Direct and indirect measurements of enhanced phenolic bioavailability from litchi pericarp procyanidins by Lactobacillus casei-01. Food Funct 2017; 8:2760-2770. [DOI: 10.1039/c7fo00749c] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Litchi pericarp procyanidins (LPP) are dietary supplements with high antioxidant activity, but poor oral bioavailability and efficacy, that can be enhanced by probiotics addition.
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Affiliation(s)
- Shuyi Li
- College of Food Science and Engineering
- Wuhan Polytechnic University
- Wuhan 430023
- PR China
| | - Xiaopeng Li
- College of Food Science and Technology
- Huazhong Agricultural University
- Wuhan 430070
- PR China
| | - Avi Shpigelman
- Faculty of Biotechnology and Food Engineering
- Technion
- Israel Institute of Technology
- Haifa
- Israel
| | - Jose M. Lorenzo
- Centro Tecnológico de la Carne de Galicia
- 32900 San Ciprián de Viñas
- Spain
| | - Domenico Montesano
- Dipartimento di Scienze Farmaceutiche
- Sezione di Scienza degli Alimenti e Nutrizione
- Università di Perugia
- Perugia
- Italy
| | - Francisco J. Barba
- Nutrition and Food Science Area
- Preventive Medicine and Public Health
- Food Sciences
- Toxicology and Forensic Medicine Department
- Faculty of Pharmacy
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Rocha BS, Nunes C, Laranjinha J. Tuning constitutive and pathological inflammation in the gut via the interaction of dietary nitrate and polyphenols with host microbiome. Int J Biochem Cell Biol 2016; 81:393-402. [PMID: 27989963 DOI: 10.1016/j.biocel.2016.10.021] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Revised: 10/22/2016] [Accepted: 10/26/2016] [Indexed: 02/08/2023]
Abstract
Chronic inflammation is currently recognized as a critical process in modern-era epidemics such as diabetes, obesity and neurodegeneration. However, little attention is paid to the constitutive inflammatory pathways that operate in the gut and that are mandatory for local welfare and the prevention of such multi-organic diseases. Hence, the digestive system, while posing as a barrier between the external environment and the host, is crucial for the balance between constitutive and pathological inflammatory events. Gut microbiome, a recently discovered organ, is now known to govern the interaction between exogenous agents and the host with ensued impact on local and systemic homeostasis. Whereas gut microbiota may be modulated by a myriad of factors, diet constitutes one of its major determinants. Thus, dietary compounds that influence microbial flora may thereby impact on inflammatory pathways. One such example is the redox environment in the gut lumen which is highly dependent on the local generation of nitric oxide along the nitrate-nitrite-nitric oxide pathway and that is further enhanced by simultaneous consumption of polyphenols. In this paper, different pathways encompassing the interaction of dietary nitrate and polyphenols with gut microbiota will be presented and discussed in connection with local and systemic inflammatory events. Furthermore, it will be discussed how these interactive cycles (nitrate-polyphenols-microbiome) may pose as novel strategies to tackle inflammatory diseases.
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Affiliation(s)
- Bárbara S Rocha
- Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, Health Sciences Campus, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal
| | - Carla Nunes
- Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, Health Sciences Campus, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal
| | - João Laranjinha
- Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, Health Sciences Campus, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
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Shanmugam T, Selvaraj M, Poomalai S. Epigallocatechin gallate potentially abrogates fluoride induced lung oxidative stress, inflammation via Nrf2/Keap1 signaling pathway in rats: An in-vivo and in-silico study. Int Immunopharmacol 2016; 39:128-139. [DOI: 10.1016/j.intimp.2016.07.022] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2016] [Revised: 07/04/2016] [Accepted: 07/20/2016] [Indexed: 12/25/2022]
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Hudlikar RR, Venkadakrishnan VB, Kumar R, Thorat RA, Kannan S, Ingle AD, Desai S, Maru GB, Mahimkar MB. Polymeric black tea polyphenols (PBPs) inhibit benzo(a)pyrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone-induced lung carcinogenesis potentially through down-regulation of p38 and Akt phosphorylation in A/J mice. Mol Carcinog 2016; 56:625-640. [DOI: 10.1002/mc.22521] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Revised: 06/22/2016] [Accepted: 07/01/2016] [Indexed: 11/08/2022]
Affiliation(s)
- Rasika R. Hudlikar
- Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC); Tata Memorial Centre (TMC), Kharghar; Navi Mumbai India
| | - Varadha Balaji Venkadakrishnan
- Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC); Tata Memorial Centre (TMC), Kharghar; Navi Mumbai India
| | - Rajiv Kumar
- Department of Pathology, Tata Memorial Hospital; Tata Memorial Centre (TMC); Parel Mumbai India
| | - Rahul A. Thorat
- Laboratory Animal Facility, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC); Tata Memorial Centre (TMC), Kharghar; Navi Mumbai India
| | - Sadhana Kannan
- Epidemiology and Clinical Trial Unit (ECTU), Advanced Centre for Treatment, Research and Education in Cancer (ACTREC); Tata Memorial Centre (TMC), Kharghar; Navi Mumbai India
| | - Arvind D. Ingle
- Laboratory Animal Facility, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC); Tata Memorial Centre (TMC), Kharghar; Navi Mumbai India
| | - Saral Desai
- Department of Pathology, Tata Memorial Hospital; Tata Memorial Centre (TMC); Parel Mumbai India
| | - Girish B. Maru
- Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC); Tata Memorial Centre (TMC), Kharghar; Navi Mumbai India
| | - Manoj B. Mahimkar
- Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC); Tata Memorial Centre (TMC), Kharghar; Navi Mumbai India
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Maru GB, Hudlikar RR, Kumar G, Gandhi K, Mahimkar MB. Understanding the molecular mechanisms of cancer prevention by dietary phytochemicals: From experimental models to clinical trials. World J Biol Chem 2016; 7:88-99. [PMID: 26981198 PMCID: PMC4768127 DOI: 10.4331/wjbc.v7.i1.88] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 09/04/2015] [Accepted: 11/25/2015] [Indexed: 02/05/2023] Open
Abstract
Chemoprevention is one of the cancer prevention approaches wherein natural/synthetic agent(s) are prescribed with the aim to delay or disrupt multiple pathways and processes involved at multiple steps, i.e., initiation, promotion, and progression of cancer. Amongst environmental chemopreventive compounds, diet/beverage-derived components are under evaluation, because of their long history of exposure to humans, high tolerability, low toxicity, and reported biological activities. This compilation briefly covers and compares the available evidence on chemopreventive efficacy and probable mechanism of chemoprevention by selected dietary phytochemicals (capsaicin, curcumin, diallyl sulphide, genistein, green/black tea polyphenols, indoles, lycopene, phenethyl isocyanate, resveratrol, retinoids and tocopherols) in experimental systems and clinical trials. All the dietary phytochemicals covered in this review have demonstrated chemopreventive efficacy against spontaneous or carcinogen-induced experimental tumors and/or associated biomarkers and processes in rodents at several organ sites. The observed anti-initiating, anti-promoting and anti-progression activity of dietary phytochemicals in carcinogen-induced experimental models involve phytochemical-mediated redox changes, modulation of enzymes and signaling kinases resulting to effects on multiple genes and cell signaling pathways. Results from clinical trials using these compounds have not shown them to be chemopreventive. This may be due to our: (1) inability to reproduce the exposure conditions, i.e., levels, complexity, other host and lifestyle factors; and (2) lack of understanding about the mechanisms of action and agent-mediated toxicity in several organs and physiological processes in the host. Current research efforts in addressing the issues of exposure conditions, bioavailability, toxicity and the mode of action of dietary phytochemicals may help address the reason for observed mismatch that may ultimately lead to identification of new chemopreventive agents for protection against broad spectrum of exposures.
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Preexposure to Olive Oil Polyphenols Extract Increases Oxidative Load and Improves Liver Mass Restoration after Hepatectomy in Mice via Stress-Sensitive Genes. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2016; 2016:9191407. [PMID: 26925195 PMCID: PMC4746397 DOI: 10.1155/2016/9191407] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/09/2015] [Revised: 12/09/2015] [Accepted: 12/13/2015] [Indexed: 12/30/2022]
Abstract
Polyphenols can act as oxidants in some conditions, inducing redox-sensitive genes. We investigated the effect of preexposure to the olive oil polyphenols extract (PFE) on time-dependent changes in the hepatic oxidative state in a model of liver regeneration—a process in which oxidative stress associated with the metabolic overload accounts for the early events that contribute to the onset of liver self-repair. Liver regeneration was induced by one-third hepatectomy in mice. Prior to hepatectomy, mice were intraperitoneally given either PFE (50 mg/kg body weight) or saline for seven consecutive days, while respective controls received vehicle alone. Redox state-regulating enzymes and thiol proteins along with the mRNA levels of Nrf2 gene and its targets γ-glutamylcysteine synthetase and heme oxygenase-1 were determined at different time intervals after hepatectomy. The liver mass restoration was calculated to assess hepatic regeneration. The resulting data demonstrate the effectiveness of preexposure to PFE in stimulating liver regeneration in a model of a small tissue loss which may be ascribed to the transient increase in oxidant load during the first hours after hepatectomy and associated induction of stress response gene-profiles under the control of Nrf2.
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Nunes C, Teixeira N, Serra D, Freitas V, Almeida L, Laranjinha J. Red wine polyphenol extract efficiently protects intestinal epithelial cells from inflammation via opposite modulation of JAK/STAT and Nrf2 pathways. Toxicol Res (Camb) 2016; 5:53-65. [PMID: 30090326 PMCID: PMC6061778 DOI: 10.1039/c5tx00214a] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Accepted: 10/01/2015] [Indexed: 12/17/2022] Open
Abstract
The development of therapeutic approaches combining efficacy and safety represents an important goal in intestinal inflammation research. Recently, evidence has supported dietary polyphenols as useful tools in the treatment and prevention of chronic inflammatory diseases, but the mechanisms of action are still poorly understood. We here reveal molecular mechanisms underlying the anti-inflammatory action of a non-alcoholic polyphenol red wine extract (RWE), operating at complementary levels via the Janus kinase/signal transducer and activator of transcription (JAK/STAT) and Nuclear factor-erythroid 2-related factor-2 (Nrf2) pathways. RWE significantly reduced the nuclear levels of phosphorylated STAT1 and also the cellular levels of phosphorylated JAK1 induced by cytokines, suppressing the JAK/STAT inflammatory signalling cascade. In turn, RWE increased the Nrf2 nuclear level, activating the Nrf2 pathway, leading not only to an up-regulation of the heme oxygenase-1 (HO-1) expression but also to an increase of the glutamate-cysteine ligase subunit catalytic (GCLc) gene expression, enhancing the GSH synthesis, thereby counteracting GSH depletion that occurs under inflammatory conditions. Overall, data indicate that the anti-inflammatory action of RWE is exerted at complementary levels, via suppression of the JAK/STAT inflammatory pathway and positive modulation of the activity of Nrf2. These results point to the potential use of the RWE as an efficient, readily available and inexpensive therapeutic strategy in the context of gastrointestinal inflammation.
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Affiliation(s)
- Carla Nunes
- Center for Neurosciences and Cell Biology and Faculty of Pharmacy , University of Coimbra , Health Sciences Campus , Azinhaga de Santa Comba , 3000-548 Coimbra , Portugal .
| | - Natércia Teixeira
- Department of Chemistry , Faculty of Sciences , University of Porto , Portugal
| | - Diana Serra
- Center for Neurosciences and Cell Biology and Faculty of Pharmacy , University of Coimbra , Health Sciences Campus , Azinhaga de Santa Comba , 3000-548 Coimbra , Portugal .
| | - Víctor Freitas
- Department of Chemistry , Faculty of Sciences , University of Porto , Portugal
| | - Leonor Almeida
- Center for Neurosciences and Cell Biology and Faculty of Pharmacy , University of Coimbra , Health Sciences Campus , Azinhaga de Santa Comba , 3000-548 Coimbra , Portugal .
| | - João Laranjinha
- Center for Neurosciences and Cell Biology and Faculty of Pharmacy , University of Coimbra , Health Sciences Campus , Azinhaga de Santa Comba , 3000-548 Coimbra , Portugal .
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de Oliveira MR, Nabavi SM, Braidy N, Setzer WN, Ahmed T, Nabavi SF. Quercetin and the mitochondria: A mechanistic view. Biotechnol Adv 2015; 34:532-549. [PMID: 26740171 DOI: 10.1016/j.biotechadv.2015.12.014] [Citation(s) in RCA: 171] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2015] [Revised: 12/24/2015] [Accepted: 12/26/2015] [Indexed: 12/24/2022]
Abstract
Quercetin is an important flavonoid that is ubiquitously present in the diet in a variety of fruits and vegetables. It has been traditionally viewed as a potent antioxidant and anti-inflammatory molecule. However, recent studies have suggested that quercetin may exert its beneficial effects independent of its free radical-scavenging properties. Attention has been placed on the effect of quercetin on an array of mitochondrial processes. Quercetin is now recognized as a phytochemical that can modulate pathways associated with mitochondrial biogenesis, mitochondrial membrane potential, oxidative respiration and ATP anabolism, intra-mitochondrial redox status, and subsequently, mitochondria-induced apoptosis. The present review evaluates recent evidence on the ability of quercetin to interact with the abovementioned pathways, and critically analyses how, such interactions can exert protection against mitochondrial damage in response to toxicity induced by several exogenously and endogenously-produced cellular stressors, and oxidative stress in particular.
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Affiliation(s)
- Marcos Roberto de Oliveira
- Department of Chemistry, ICET, Federal University of Mato Grosso (UFMT), Av. Fernando Corrêa da Costa, 2367, CEP 78060-900, Cuiabá, MT, Brazil.
| | - Seyed Mohammad Nabavi
- Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Nady Braidy
- Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Australia
| | - William N Setzer
- Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA
| | - Touqeer Ahmed
- Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan
| | - Seyed Fazel Nabavi
- Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
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Hernández-Salinas R, Decap V, Leguina A, Cáceres P, Perez D, Urquiaga I, Iturriaga R, Velarde V. Antioxidant and anti hyperglycemic role of wine grape powder in rats fed with a high fructose diet. Biol Res 2015; 48:53. [PMID: 26420015 PMCID: PMC4588460 DOI: 10.1186/s40659-015-0045-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2015] [Accepted: 09/22/2015] [Indexed: 12/14/2022] Open
Abstract
Background Metabolic syndrome is a growing worldwide health problem. We evaluated the effects of wine grape powder (WGP), rich in antioxidants and fiber, in a rat model of metabolic syndrome induced by a high fructose diet. We tested whether WGP supplementation may prevent glucose intolerance and decrease oxidative stress in rats fed with a high fructose diet. Methods Male Sprague–Dawley rats weighing 180 g were divided into four groups according to their feeding protocols. Rats were fed with control diet (C), control plus 20 % WGP (C + WGP), 50 % high fructose (HF) or 50 % fructose plus 20 % WGP (HF + WGP) for 16 weeks. Blood glucose, insulin and triglycerides, weight, and arterial blood pressure were measured. Homeostasis model assessment (HOMA) index was calculated using insulin and glucose values. A glucose tolerance test was performed 2 days before the end of the experiment. As an index of oxidative stress, thiobarbituric acid reactive substances (TBARS) level was measured in plasma and kidney, and superoxide dismutase was measured in the kidney. Results Thiobarbituric acid reactive substances in plasma and renal tissue were significantly higher when compared to the control group. In addition, the area under the curve of the glucose tolerance test was higher in HF fed animals. Furthermore, fasting blood glucose, plasma insulin levels, and the HOMA index, were also increased. WGP supplementation prevented these alterations in rats fed with the HF diet. We did not find any significant difference in body weight or systolic blood pressure in any of the groups. Conclusions Our results show that WGP supplementation prevented hyperglycemia, insulin resistance and reduced oxidative stress in rats fed with HF diet. We propose that WGP may be used as a supplement in human food as well.
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Affiliation(s)
- Romina Hernández-Salinas
- Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
| | - Valerie Decap
- Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
| | - Alberto Leguina
- Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
| | - Patricio Cáceres
- Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
| | - Druso Perez
- Center for Molecular Nutrition and Chronic Diseases, Pontificia Universidad Católica de Chile, Santiago, Chile.
| | - Ines Urquiaga
- Center for Molecular Nutrition and Chronic Diseases, Pontificia Universidad Católica de Chile, Santiago, Chile.
| | - Rodrigo Iturriaga
- Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile. .,Center for Molecular Nutrition and Chronic Diseases, Pontificia Universidad Católica de Chile, Santiago, Chile.
| | - Victoria Velarde
- Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile. .,Center for Molecular Nutrition and Chronic Diseases, Pontificia Universidad Católica de Chile, Santiago, Chile.
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Mahmoud AM, Al Dera HS. 18β-Glycyrrhetinic acid exerts protective effects against cyclophosphamide-induced hepatotoxicity: potential role of PPARγ and Nrf2 upregulation. GENES AND NUTRITION 2015; 10:41. [PMID: 26386843 DOI: 10.1007/s12263-015-0491-1] [Citation(s) in RCA: 117] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Accepted: 09/08/2015] [Indexed: 01/06/2023]
Abstract
18β-Glycyrrhetinic acid (18β-GA) has been proposed as a promising hepatoprotective agent. The current study aimed to investigate the protective action and the possible mechanisms of 18β-GA against cyclophosphamide (CP)-induced liver injury in rats, focusing on the role of peroxisome proliferator-activated receptor gamma (PPARγ) and NF-E2-related factor-2 (Nrf2). Rats were administered 18β-GA at doses 25 and 50 mg/kg 2 weeks prior to CP injection. Five days after CP administration, animals were sacrificed and samples were collected. CP induced hepatic damage evidenced by the histopathological changes and significant increase in serum pro-inflammatory cytokines, liver marker enzymes, and liver lipid peroxidation and nitric oxide (NO) levels. 18β-GA counteracted CP-induced oxidative stress and inflammation as assessed by restoration of the antioxidant defenses and diminishing of pro-inflammatory cytokines, lipid peroxidation, and NO production. These hepatoprotective effects appear to depend on activation of Nrf2 and PPARγ, and subsequent suppression of nuclear factor-kappa B. In conclusion, the present study provides evidence that 18β-GA exerts hepatoprotective effects against CP through induction of antioxidant defenses and suppression of inflammatory response. This report also confers new information that 18β-GA protects liver against the toxic effect of chemotherapeutic alkylating agents via activation of Nrf2 and PPARγ.
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Affiliation(s)
- Ayman M Mahmoud
- Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni Suef, 62514, Egypt.
| | - Hussein S Al Dera
- Basic Medical Sciences Department, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
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Hong Y, Jiang W, Kuang S, Hu K, Tang L, Liu Y, Jiang J, Zhang Y, Zhou X, Feng L. Growth, digestive and absorptive capacity and antioxidant status in intestine and hepatopancreas of sub-adult grass carp Ctenopharyngodonidella fed graded levels of dietary threonine. J Anim Sci Biotechnol 2015; 6:34. [PMID: 26257911 PMCID: PMC4529687 DOI: 10.1186/s40104-015-0032-1] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Accepted: 07/02/2015] [Indexed: 02/01/2023] Open
Abstract
Background This study was carried out to investigate effects of threonine levels on growth, digestive and absorptive capacity and antioxidant status in intestine and hepatopancreas of sub-adult grass carp (Ctenopharyngodonidella). Results Weight gain, specific growth rate, feed intake and feed efficiency were significantly improved by dietary threonine (P < 0.05). Intestinal activities of trypsin, chymotrypsin, alpha-amylase, lipase, alkaline phosphatase, γ-glutamyl transpeptidase and creatine kinase took the similar trends. Contents of malondialdehyde and protein carbonyl in intestine and hepatopancreas were significantly decreased by dietary optimal threonine supplementation (P < 0.05). Anti-superoxide anion capacity, anti-hydroxyl radical capacity, glutathione content and activities of superoxide dismutase, catalase and glutathione-S-transferase in intestine and hepatopancreas were enhanced by dietary threonine (P < 0.05). Conclusions Dietary threonine could improve growth, enhance digestive and absorptive capacity and antioxidant status in intestine and hepatopancreas of sub-adult grass carp. The dietary threonine requirement of sub-adult grass carp (441.9-1,013.4 g) based on weight gain was 11.6 g/kg diet or 41.5 g/kg of dietary protein by quadratic regression analysis.
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Affiliation(s)
- Yang Hong
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130 Sichuan China
| | - Weidan Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130 Sichuan China ; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130 Sichuan China ; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130 Sichuan China
| | - Shengyao Kuang
- Sichuan Academy of Animal Science, Animal Nutrition Institute, Chengdu, 610066 China
| | - Kai Hu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130 Sichuan China ; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130 Sichuan China ; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130 Sichuan China
| | - Ling Tang
- Sichuan Academy of Animal Science, Animal Nutrition Institute, Chengdu, 610066 China
| | - Yang Liu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130 Sichuan China ; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130 Sichuan China ; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130 Sichuan China
| | - Jun Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130 Sichuan China ; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130 Sichuan China ; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130 Sichuan China
| | - Yongan Zhang
- Chinese Academy of Sciences, Institute of Hydrobiology, Wuhan, 430072 China
| | - Xiaoqiu Zhou
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130 Sichuan China ; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130 Sichuan China ; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130 Sichuan China
| | - Lin Feng
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130 Sichuan China ; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130 Sichuan China ; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130 Sichuan China
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Tea consumption and mortality of all cancers, CVD and all causes: a meta-analysis of eighteen prospective cohort studies. Br J Nutr 2015. [PMID: 26202661 DOI: 10.1017/s0007114515002329] [Citation(s) in RCA: 85] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Epidemiological studies have demonstrated inconsistent associations between tea consumption and mortality of all cancers, CVD and all causes. To obtain quantitative overall estimates, we conducted a dose-response meta-analysis of prospective cohort studies. A literature search in PubMed and Embase up to April 2015 was conducted for all relevant papers published. Random-effects models were used to calculate pooled relative risks (RR) with 95 % CI. In eighteen prospective studies, there were 12 221, 11 306 and 55 528 deaths from all cancers, CVD and all causes, respectively. For all cancer mortality, the summary RR for the highest v. lowest category of green tea and black tea consumption were 1·06 (95 % CI 0·98, 1·15) and 0·79 (95 % CI 0·65, 0·97), respectively. For CVD mortality, the summary RR for the highest v. lowest category of green tea and black tea consumption were 0·67 (95 % CI 0·46, 0·96) and 0·88 (95 % CI 0·77, 1·01), respectively. For all-cause mortality, the summary RR for the highest v. lowest category of green tea and black tea consumption were 0·80 (95 % CI 0·68, 0·93) and 0·90 (95 % CI 0·83, 0·98), respectively. The dose-response analysis indicated that one cup per d increment of green tea consumption was associated with 5 % lower risk of CVD mortality and with 4 % lower risk of all-cause mortality. Green tea consumption was significantly inversely associated with CVD and all-cause mortality, whereas black tea consumption was significantly inversely associated with all cancer and all-cause mortality.
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Butt MS, Imran A, Sharif MK, Ahmad RS, Xiao H, Imran M, Rsool HA. Black tea polyphenols: a mechanistic treatise. Crit Rev Food Sci Nutr 2014; 54:1002-11. [PMID: 24499118 DOI: 10.1080/10408398.2011.623198] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Dietary interventions are among the emerging trends to curtail physiological malfunctioning like cancer, diabetes, cardiac complications, etc. The essence of phytonutrients has developed the concept of nutraceuticals at the junction of diet health linkages. In this context, theaflavin & thearubigins are the oxidized derivatives of black tea catechins during fermentation having nutraceutical potential owing to esterification of hydroxyl ring with digallate esters. Theaflavin may influence activation of transcription factors such as NFnB or AP-1 that ultimately hinder the formation of nitric oxide expression gene. Likewise, black tea contains a unique amino acid theanine acts as neurotransmitter owing to its ability to cross the blood-brain barrier. Moreover, it boasts immunity by enhancing the disease-fighting ability of gamma delta T cells. Theaflavin & thearubigins act as safeguard against oxidative stress thereby effective in the cardiac functioning. The mechanistic approach of these antioxidants is likely to be associated with inhibition of redox sensitive transcription factors & pro-oxidant enzymes such as xanthine oxidase or nitric oxide synthase. However, their involvement in antioxidative enzyme induction as in glutathione-S-transferases is also well documented. They act as curative agent against numerous pathological disorders by disrupting the electron chain thus inhibiting the progression of certain ailments. Black tea polyphenols established themselves as strong antioxidants due to their standard one-electron potential, and their vitality is dependent on the concentration of polyphenols and pH for their inclusive execution. Present review is an attempt to enrich the readers regarding the health promoting aspects of black tea polyphenols. Concomitantly, it needs core attention of researchers for the exploitations of black tea flavanols as an important dietary constituent for the vulnerable segment.
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Affiliation(s)
- M S Butt
- a National Institute of Food Science and Technology , University of Agriculture , Faisalabad , Pakistan
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Sarkar A, Sil PC. Iron oxide nanoparticles mediated cytotoxicity via PI3K/AKT pathway: role of quercetin. Food Chem Toxicol 2014; 71:106-115. [PMID: 24937022 DOI: 10.1016/j.fct.2014.06.003] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2014] [Revised: 06/06/2014] [Accepted: 06/07/2014] [Indexed: 12/11/2022]
Abstract
Recently Fe2O3 NPs (iron oxide nanoparticles) have been extensively used in medical imaging and in industry also. As a result, people are increasingly exposed day by day to those nanoparticles. The adverse effect of Fe2O3 NPs is not so significant at lower doses but at higher doses Fe2O3 NPs causes significant damage to cells. The present study investigates the cell signaling mechanism of Fe2O3 NPs induced oxidative stress and cytotoxicity in vitro using murine hepatocytes as the working model. In addition, the cytoprotective action of quercetin in this pathophysiology has also been investigated. Dose-dependent studies suggest that incubation of hepatocytes with 250 μg/ml Fe2O3 NPs for 4h significantly decreased the cell viability and intra-cellular antioxidant ability. This study also showed that exposure to Fe2O3 NPs caused hepatocytes death via apoptotic pathway. Incubation of hepatocytes with quercetin (50 μmol/L) prior to 1h of Fe2O3 NPs exposure protects the cells from the altering activities of antioxidant indices, cytotoxicity and apoptotic death. Results suggest that Fe2O3 NPs induced cellular damage and quercetin plays a protective role in Fe2O3 NPs induced cytotoxicity and apoptotic death.
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Affiliation(s)
- Abhijit Sarkar
- Division of Molecular Medicine, Bose Institute, Kolkata 700054, India
| | - Parames C Sil
- Division of Molecular Medicine, Bose Institute, Kolkata 700054, India.
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Effect of commercially available green and black tea beverages on drug-metabolizing enzymes and oxidative stress in Wistar rats. Food Chem Toxicol 2014; 70:120-7. [DOI: 10.1016/j.fct.2014.04.043] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2013] [Revised: 04/26/2014] [Accepted: 04/30/2014] [Indexed: 01/25/2023]
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Kumar H, Kim IS, More SV, Kim BW, Choi DK. Natural product-derived pharmacological modulators of Nrf2/ARE pathway for chronic diseases. Nat Prod Rep 2014; 31:109-39. [DOI: 10.1039/c3np70065h] [Citation(s) in RCA: 248] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Lambert JD. Does tea prevent cancer? Evidence from laboratory and human intervention studies. Am J Clin Nutr 2013; 98:1667S-1675S. [PMID: 24172300 DOI: 10.3945/ajcn.113.059352] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Tea (Camellia sinensis) is a widely consumed beverage and has been extensively studied for its cancer-preventive activity. Both the polyphenolic constituents as well as the caffeine in tea have been implicated as potential cancer-preventive compounds; the relative importance seems to depend on the cancer type. Green tea and the green tea catechin have been shown to inhibit tumorigenesis at a number of organ sites and to be effective when administered either during the initiation or postinitiation phases of carcinogenesis. Black tea, although not as well studied as green tea, has also shown cancer-preventive effects in laboratory models. A number of potential mechanisms have been proposed to account for the cancer-preventive effects of tea, including modulation of phase II metabolism, alterations in redox environment, inhibition of growth factor signaling, and others. In addition to the laboratory studies, there is a growing body of human intervention studies suggesting that tea can slow cancer progression and modify biomarkers relevant to carcinogenesis. Although available data are promising, many questions remain with regard to the dose-response relations of tea constituents in various models, the primary mechanisms of action, and the potential for combination chemoprevention strategies that involve tea as well as other dietary or pharmaceutical agents. The present review examines the available data from laboratory animal and human intervention studies on tea and cancer prevention. These data were evaluated, and areas for further research are identified.
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Affiliation(s)
- Joshua D Lambert
- Center of Excellence for Plant and Mushroom Foods for Health, the Department of Food Science, Pennsylvania State University, University Park, PA
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Estrela JM, Ortega A, Mena S, Rodriguez ML, Asensi M. Pterostilbene: Biomedical applications. Crit Rev Clin Lab Sci 2013; 50:65-78. [DOI: 10.3109/10408363.2013.805182] [Citation(s) in RCA: 102] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Dietz BM, Hagos GK, Eskra JN, Wijewickrama GT, Anderson JR, Nikolic D, Guo J, Wright B, Chen SN, Pauli GF, van Breemen RB, Bolton JL. Differential regulation of detoxification enzymes in hepatic and mammary tissue by hops (Humulus lupulus) in vitro and in vivo. Mol Nutr Food Res 2013; 57:1055-66. [PMID: 23512484 PMCID: PMC3864769 DOI: 10.1002/mnfr.201200534] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2012] [Revised: 12/21/2012] [Accepted: 01/03/2013] [Indexed: 12/21/2022]
Abstract
SCOPE Hops contain the phytoestrogen, 8-prenylnaringenin, and the cytoprotective compound, xanthohumol (XH). XH induces the detoxification enzyme, NAD(P)H-quinone oxidoreductase (NQO1) in vitro; however, the tissue distribution of XH and 8-prenylnaringenin and their tissue-specific activity have not been analyzed. METHODS AND RESULTS An orally administered hop extract and subcutaneously injected XH were administered to Sprague-Dawley rats over 4 days. LC-MS-MS analysis of plasma, liver, and mammary gland revealed that XH accumulated in liver and mammary glands. Compared with the low level in the original extract, 8-prenylnaringenin was enriched in the tissues. Hops and XH-induced NQO1 in the liver, while only hops reduced NQO1 activity in the mammary gland. Mechanistic studies revealed that hops modulated NQO1 through three mechanisms. In liver cells, (i) XH modified Kelch-like ECH-associated protein leading to nuclear factor (erythroid-derived 2)-like 2 (Nrf2) translocation and antioxidant response element (ARE) activation; (ii) hop-mediated ARE induction was partially mediated through phosphorylation of Nrf2 by PKC; (iii) in breast cells, 8-prenylnaringenin reduced NQO1 likely through binding to estrogen receptorα, recruiting Nrf2, and downregulating ARE-regulated genes. CONCLUSION XH and 8-prenylnaringenin in dietary hops are bioavailable to the target tissues. While hops and XH might be cytoprotective in the liver, 8-prenylnaringenin seems responsible for hop-mediated NQO1 reduction in the mammary gland.
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Affiliation(s)
- Birgit M Dietz
- UIC/NIH Center for Botanical Dietary Supplements Research, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612, USA.
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Kavitha K, Thiyagarajan P, Rathna Nandhini J, Mishra R, Nagini S. Chemopreventive effects of diverse dietary phytochemicals against DMBA-induced hamster buccal pouch carcinogenesis via the induction of Nrf2-mediated cytoprotective antioxidant, detoxification, and DNA repair enzymes. Biochimie 2013; 95:1629-39. [PMID: 23707664 DOI: 10.1016/j.biochi.2013.05.004] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2012] [Accepted: 05/13/2013] [Indexed: 01/27/2023]
Abstract
Identifying agents that activate nuclear factor erythroid-2 related factor-2 (Nrf2), a key regulator of various cytoprotective antioxidant, and detoxifying enzymes has evolved as a promising strategy for cancer chemoprevention. In the present study, we investigated the effect of dietary supplementation of structurally diverse phytochemicals- astaxanthin, blueberry, chlorophyllin, ellagic acid, and theaphenon-E on Nrf2 signaling, and xenobiotic-metabolizing and antioxidant enzymes in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model. We observed that these phytochemicals induce nuclear accumulation of Nrf2 while downregulating its negative regulator, Keap-1. This was associated with reduced expression of CYP1A1 and CYP1B1, the cytochrome P450 isoforms involved in the activation of DMBA, and the oxidative stress marker 8-hydroxy-2'-deoxyguanosine coupled with upregulation of the phase II detoxification enzymes glutathione S-transferases and NAD(P)H:quinone oxidoreductase 1 and the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase. In addition, these dietary phytochemicals also enhanced the DNA repair enzymes 8-oxoguanine glycosylase 1 (OGG1), xeroderma pigmentosum D (XPD), xeroderma pigmentosum G (XPG), and x-ray repair cross complementing group 1 (XRCC1). Our data provide substantial evidence that the dietary phytochemicals inhibit the development of HBP carcinomas through the activation of Nrf2/Keap-1 signaling and by upregulating cytoprotective enzymes. The extent of the chemopreventive effects of the phytochemicals was in the order: chlorophyllin > blueberry > ellagic acid > astaxanthin > theaphenon-E. Thus these dietary phytochemicals that function as potent activators of Nrf2 and its orchestrated response are novel candidates for cancer chemoprevention.
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Affiliation(s)
- K Kavitha
- Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, India
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The involvement of NRF2 in lung cancer. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2013; 2013:746432. [PMID: 23577226 PMCID: PMC3614183 DOI: 10.1155/2013/746432] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/08/2013] [Revised: 02/20/2013] [Accepted: 02/26/2013] [Indexed: 12/22/2022]
Abstract
Nuclear factor, erythroid-derived 2, like 2 (NRF2) is a key regulator of antioxidants and cellular stress responses. The role of NRF2 in pulmonary neoplasia, a diverse disease for which few biomarkers exist, is complicated and appears to depend on several main factors including the existence of activating mutations in NRF2 and/or loss of function mutations in KEAP1 and the stage of carcinogenesis studied, particularly in the mouse models tested. Therapeutic strategies for lung cancer targeting NRF2 have observed mixed results, both anti- and protumorigenic effects; however, these differences seem to reflect the mutation status of NRF2 or KEAP1. In this paper, we will discuss the studies on human NRF2 and the mechanisms proposed, several mouse models using various mice deficient in NRF2, as well as xenograft models, and the chemotherapeutic strategies using the NRF2 pathway.
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Supplementation of a grape seed and grape marc meal extract decreases activities of the oxidative stress-responsive transcription factors NF-κB and Nrf2 in the duodenal mucosa of pigs. Acta Vet Scand 2013; 55:18. [PMID: 23453040 PMCID: PMC3599961 DOI: 10.1186/1751-0147-55-18] [Citation(s) in RCA: 98] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2012] [Accepted: 02/24/2013] [Indexed: 12/23/2022] Open
Abstract
Background In pigs, enteric infections and the development of gut disorders such as diarrhoea are commonly observed, particularly after weaning. The present study investigated the hypothesis that feeding a grape seed and grape marc extract (GSGME) as a dietary supplement has the potential to suppress the inflammatory process in the small intestine of pigs by modulating the activities of NF-κB and Nrf2 due to its high content of flavonoids. Methods Twenty-four crossbred, 6 weeks old pigs were randomly assigned to 2 groups of 12 animals each and fed nutritionally adequate diets without or with 1% GSGME for 4 weeks. Results Pigs administered GSGME had a lower transactivation of NF-κB and Nrf2 and a lower expression of various target genes of these transcription factors in the duodenal mucosa than control pigs (P < 0.05). Concentrations of α-tocopherol and thiobarbituric acid reactive substances (TBARS) in liver and plasma and total antioxidant capacity of plasma and relative mRNA abundances of NF-κB and Nrf2 target genes in the liver did not differ between the two groups. However, the ratio of villus height:crypt depth and the gain:feed ratio was higher in the pigs fed GSGME than in control pigs (P < 0.05). Conclusions This study shows that dietary supplementation of a polyphenol rich GSGME suppresses the activity of NF-κB in the duodenal mucosa of pigs and thus might provide a useful dietary strategy to inhibit inflammation in the gut frequently occurring in pigs. Feeding GSGME did not influence vitamin E status and the antioxidant system of the pigs but improved the gain:feed ratio. In overall, the study suggests that polyphenol-rich plant extracts such GSGME could be useful feed supplements in pig nutrition, in order to maintain animal health and improve performance.
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Chen S, Zou L, Li L, Wu T. The protective effect of glycyrrhetinic acid on carbon tetrachloride-induced chronic liver fibrosis in mice via upregulation of Nrf2. PLoS One 2013; 8:e53662. [PMID: 23341968 PMCID: PMC3544925 DOI: 10.1371/journal.pone.0053662] [Citation(s) in RCA: 106] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2012] [Accepted: 12/03/2012] [Indexed: 12/22/2022] Open
Abstract
This study was designed to investigate the potentially protective effects of glycyrrhetinic acid (GA) and the role of transcription factor nuclear factor-erythroid 2(NF-E2)-related factor 2 (Nrf2) signaling in the regulation of Carbon Tetrachloride (CCl4)-induced chronic liver fibrosis in mice. The potentially protective effects of GA on CCl4-induced chronic liver fibrosis in mice were depicted histologically and biochemically. Firstly, histopathological changes including regenerative nodules, inflammatory cell infiltration and fibrosis were induced by CCl4.Then, CCl4 administration caused a marked increase in the levels of serum aminotransferases (GOT, GPT), serum monoamine oxidase (MAO) and lipid peroxidation (MDA) as well as MAO in the mice liver homogenates. Also, decreased nuclear Nrf2 expression, mRNA levels of its target genes such as superoxide dismutase 3 (SOD3), catalase (CAT), glutathione peroxidase 2 (GPX2), and activity of cellular antioxidant enzymes were found after CCl4 exposure. All of these phenotypes were markedly reversed by the treatment of the mice with GA. In addition, GA exhibited the antioxidant effects in vitro by on FeCl2-ascorbate induced lipid peroxidation in mouse liver homogenates, and on DPPH scavenging activity. Taken together, these results suggested that GA can protect the liver from oxidative stress in mice, presumably through activating the nuclear translocation of Nrf2, enhancing the expression of its target genes and increasing the activity of the antioxidant enzymes. Therefore, GA may be an effective hepatoprotective agent and viable candidate for treating liver fibrosis and other oxidative stress-related diseases.
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Affiliation(s)
- Shaoru Chen
- The Pharmacy of GuangDong Medical College, DongGuan, GuangDong, China
| | - Liyi Zou
- The Pharmacy of GuangDong Medical College, DongGuan, GuangDong, China
| | - Li Li
- The Pharmacy of GuangDong Medical College, DongGuan, GuangDong, China
| | - Tie Wu
- The Pharmacy of GuangDong Medical College, DongGuan, GuangDong, China
- * E-mail:
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The effects of polyphenols on oxidative stress and the arachidonic acid cascade. Implications for the prevention/treatment of high prevalence diseases. Biochem Pharmacol 2012; 84:1113-22. [DOI: 10.1016/j.bcp.2012.07.017] [Citation(s) in RCA: 90] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2012] [Revised: 07/17/2012] [Accepted: 07/17/2012] [Indexed: 11/22/2022]
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Kumar G, Dange P, Kailaje V, Vaidya MM, Ramchandani AG, Maru GB. Polymeric black tea polyphenols modulate the localization and activity of 12-O-tetradecanoylphorbol-13-acetate-mediated kinases in mouse skin: mechanisms of their anti-tumor-promoting action. Free Radic Biol Med 2012; 53:1358-70. [PMID: 22841871 DOI: 10.1016/j.freeradbiomed.2012.07.017] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2012] [Revised: 07/05/2012] [Accepted: 07/17/2012] [Indexed: 02/06/2023]
Abstract
Polymeric black tea polyphenols (PBPs) have been shown to possess anti-tumor-promoting effects in two-stage skin carcinogenesis. However, their mechanisms of action are not fully elucidated. In this study, mechanisms of PBP-mediated antipromoting effects were investigated in a mouse model employing the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Compared to controls, a single topical application of TPA to mouse skin increased the translocation of protein kinase C (PKC) from cytosol to membrane. Pretreatment with PBPs 1-3 decreased TPA-induced translocation of PKC isozymes (α, β, η, γ, ε) from cytosol to membrane, whereas PBPs 4 and 5 were less effective. The levels of PKCs δ and ζ in cytosol/membrane were similar in all the treatment groups. Complementary confocal microscopic evaluation showed a decrease in TPA-induced PKCα fluorescence in PBP-3-pretreated membranes, whereas pretreatment with PBP-5 did not show a similar decrease. Based on the experiments with specific enzyme inhibitors and phosphospecific antibodies, both PBP-3 and PBP-5 were observed to decrease TPA-induced level and/or activity of phosphatidylinositol 3-kinase (PI3K) and AKT1 (pS473). An additional ability of PBP-3 to inhibit site-specific phosphorylation of PKCα at all three positions responsible for its activation [PKCα (pT497), PKC PAN (βII pS660), PKCα/βII (pT638/641)] and AKT1 at the Thr308 position, along with a decrease in TPA-induced PDK1 protein level, correlated with the inhibition of translocation of PKC, which may impart relatively stronger chemoprotective activity to PBP-3 than to PBP-5. Altogether, PBP-mediated decrease in TPA-induced PKC phosphorylation correlated well with decreased TPA-induced NF-κB phosphorylation and downstream target proteins associated with proliferation, apoptosis, and inflammation in mouse skin. Results suggest that the antipromoting effects of PBPs are due to modulation of TPA-induced PI3K-mediated signal transduction.
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Affiliation(s)
- Gaurav Kumar
- Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, India
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Das J, Ghosh J, Roy A, Sil PC. Mangiferin exerts hepatoprotective activity against D-galactosamine induced acute toxicity and oxidative/nitrosative stress via Nrf2-NFκB pathways. Toxicol Appl Pharmacol 2012; 260:35-47. [PMID: 22310181 DOI: 10.1016/j.taap.2012.01.015] [Citation(s) in RCA: 132] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2011] [Revised: 01/06/2012] [Accepted: 01/07/2012] [Indexed: 12/19/2022]
Abstract
Mangiferin, a xanthone glucoside, is well known to exhibit antioxidant, antiviral, antitumor, anti-inflammatory and gene-regulatory effects. In the present study, we isolated mangiferin from the bark of Mangifera indica and assessed its beneficial role in galactosamine (GAL) induced hepatic pathophysiology. GAL (400 mg/kg body weight) exposed hepatotoxic rats showed elevation in the activities of serum ALP, ALT, levels of triglycerides, total cholesterol, lipid-peroxidation and reduction in the levels of serum total proteins, albumin and cellular GSH. Besides, GAL exposure (5 mM) in hepatocytes induced apoptosis and necrosis, increased ROS and NO production. Signal transduction studies showed that GAL exposure significantly increased the nuclear translocation of NFκB and elevated iNOS protein expression. The same exposure also elevated TNF-α, IFN-γ, IL-1β, IL-6, IL-12, IL-18 and decreased IL-10 mRNA expressions. Furthermore, GAL also decreased the protein expression of Nrf2, NADPH:quinine oxidoreductase-1, heme oxygenase-1 and GSTα. However, mangiferin administration in GAL intoxicated rats or coincubation of hepatocytes with mangiferin significantly altered all these GAL-induced adverse effects. In conclusion, the hepatoprotective role of mangiferin was due to induction of antioxidant defense via the Nrf2 pathway and reduction of inflammation via NFκB inhibition.
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Affiliation(s)
- Joydeep Das
- Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054, India
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