|
1
|
Ronasi S, Mahdavi AH, Varnosfaderani SR, Kowsar R, Jafarpour F, Nasr-Esfahani MH. Punicic acid alleviates methylglyoxal-induced oocyte dysfunction during in vitro maturation in mouse species. PLoS One 2025; 20:e0314602. [PMID: 40131868 PMCID: PMC11936299 DOI: 10.1371/journal.pone.0314602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 11/12/2024] [Indexed: 03/27/2025] Open
Abstract
Dicarbonyl stress, characterized by the abnormal accumulation of reactive dicarbonyl metabolites and advanced glycation end-products (AGEs), is implicated in various pathological conditions, including obesity, diabetes, and reproductive disorders. Methylglyoxal (MGO), a highly reactive dicarbonyl metabolite, has been shown to compromise oocyte quality and developmental competence. In this study, we investigated the protective role of punicic acid (PA), a potent antioxidant found in pomegranate seed oil, against MGO-induced oocyte dysfunction. Our findings revealed that 75 µM MGO exposure during in vitro oocyte maturation significantly reduced the maturation rate and impaired subsequent embryonic development, characterized by decreased pronucleus formation and blastocyst rates. Interestingly, PA supplementation partially ameliorated these adverse effects of MGO, highlighting its potential as a protective agent against dicarbonyl-induced oocyte dysfunction. Co-treatment with PA restored the imbalanced redox state induced by MGO, leading to reduction in ROS levels and an increase in GSH levels in matured oocytes. Additionally, co-supplementation with PA preserved mitochondrial distribution in oocytes challenged with MGO, further contributing to improved oocyte quality. At the molecular level, PA co-treatment modulated the expression of genes involved in dicarbonyl stress and oxidative responses, including Glo1, Rage, Nrf2, and Nf-κB, potentially regulating the detoxification of MGO and mitigating its harmful effects. Lastly, PA supplementation improved cell lineage allocation in blastocysts developed from MGO-challenged oocytes, emphasizing its role in enhancing the quality of preimplantation embryos. In conclusion, our study provides novel insights into the protective effects of punicic acid as an antioxidant against MGO-induced oocyte dysfunction, suggesting its potential as a dietary intervention to enhance reproductive health, particularly in individuals facing dicarbonyl stress-associated conditions such as obesity and diabetes.
Collapse
Affiliation(s)
- Shahrzad Ronasi
- Department of Animal Science, College of Agriculture, Isfahan University of Technology, Isfahan, Iran
| | - Amir Hossein Mahdavi
- Department of Animal Science, College of Agriculture, Isfahan University of Technology, Isfahan, Iran
| | - Shiva Rouhollahi Varnosfaderani
- Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Rasoul Kowsar
- Department of Animal Science, College of Agriculture, Isfahan University of Technology, Isfahan, Iran
| | - Farnoosh Jafarpour
- Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Mohammad Hossein Nasr-Esfahani
- Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| |
Collapse
|
|
2
|
Cheng X, Tan Y, Li H, Zhang Z, Hui S, Zhang Z, Peng W. Mechanistic Insights and Potential Therapeutic Implications of NRF2 in Diabetic Encephalopathy. Mol Neurobiol 2024; 61:8253-8278. [PMID: 38483656 DOI: 10.1007/s12035-024-04097-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Accepted: 03/04/2024] [Indexed: 09/21/2024]
Abstract
Diabetic encephalopathy (DE) is a complication of diabetes, especially type 2 diabetes (T2D), characterized by damage in the central nervous system and cognitive impairment, which has gained global attention. Despite the extensive research aimed at enhancing our understanding of DE, the underlying mechanism of occurrence and development of DE has not been established. Mounting evidence has demonstrated a close correlation between DE and various factors, such as Alzheimer's disease-like pathological changes, insulin resistance, inflammation, and oxidative stress. Of interest, nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor with antioxidant properties that is crucial in maintaining redox homeostasis and regulating inflammatory responses. The activation and regulatory mechanisms of NRF2 are a relatively complex process. NRF2 is involved in the regulation of multiple metabolic pathways and confers neuroprotective functions. Multiple studies have provided evidence demonstrating the significant involvement of NRF2 as a critical transcription factor in the progression of DE. Additionally, various molecules capable of activating NRF2 expression have shown potential in ameliorating DE. Therefore, it is intriguing to consider NRF2 as a potential target for the treatment of DE. In this review, we aim to shed light on the role and the possible underlying mechanism of NRF2 in DE. Furthermore, we provide an overview of the current research landscape and address the challenges associated with using NRF2 activators as potential treatment options for DE.
Collapse
Affiliation(s)
- Xin Cheng
- Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China
- National Clinical Research Center for Mental Disorder, Changsha, 410011, China
| | - Yejun Tan
- School of Mathematics, University of Minnesota, Twin Cities, Minneapolis, MN, USA
| | - Hongli Li
- Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China
- National Clinical Research Center for Mental Disorder, Changsha, 410011, China
| | - Zhen Zhang
- YangSheng College of Traditional Chinese Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, Guizhou, China
| | - Shan Hui
- Department of Geratology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, China
| | - Zheyu Zhang
- Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.
- National Clinical Research Center for Mental Disorder, Changsha, 410011, China.
| | - Weijun Peng
- Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.
- National Clinical Research Center for Mental Disorder, Changsha, 410011, China.
| |
Collapse
|
|
3
|
Hellwig M, Diel P, Eisenbrand G, Grune T, Guth S, Henle T, Humpf HU, Joost HG, Marko D, Raupbach J, Roth A, Vieths S, Mally A. Dietary glycation compounds - implications for human health. Crit Rev Toxicol 2024; 54:485-617. [PMID: 39150724 DOI: 10.1080/10408444.2024.2362985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 05/24/2024] [Accepted: 05/28/2024] [Indexed: 08/17/2024]
Abstract
The term "glycation compounds" comprises a wide range of structurally diverse compounds that are formed endogenously and in food via the Maillard reaction, a chemical reaction between reducing sugars and amino acids. Glycation compounds produced endogenously are considered to contribute to a range of diseases. This has led to the hypothesis that glycation compounds present in food may also cause adverse effects and thus pose a nutritional risk to human health. In this work, the Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG) summarized data on formation, occurrence, exposure and toxicity of glycation compounds (Part A) and systematically assessed potential associations between dietary intake of defined glycation compounds and disease, including allergy, diabetes, cardiovascular and renal disease, gut/gastrotoxicity, brain/cognitive impairment and cancer (Part B). A systematic search in Pubmed (Medline), Scopus and Web of Science using a combination of keywords defining individual glycation compounds and relevant disease patterns linked to the subject area of food, nutrition and diet retrieved 253 original publications relevant to the research question. Of these, only 192 were found to comply with previously defined quality criteria and were thus considered suitable to assess potential health risks of dietary glycation compounds. For each adverse health effect considered in this assessment, however, only limited numbers of human, animal and in vitro studies were identified. While studies in humans were often limited due to small cohort size, short study duration, and confounders, experimental studies in animals that allow for controlled exposure to individual glycation compounds provided some evidence for impaired glucose tolerance, insulin resistance, cardiovascular effects and renal injury in response to oral exposure to dicarbonyl compounds, albeit at dose levels by far exceeding estimated human exposures. The overall database was generally inconsistent or inconclusive. Based on this systematic review, the SKLM concludes that there is at present no convincing evidence for a causal association between dietary intake of glycation compounds and adverse health effects.
Collapse
Affiliation(s)
- Michael Hellwig
- Chair of Special Food Chemistry, Technische Universität Dresden, Dresden, Germany
| | - Patrick Diel
- Department of Molecular and Cellular Sports Medicine, Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne, Cologne, Germany
| | | | - Tilman Grune
- Department of Molecular Toxicology, German Institute of Human Nutrition (DIfE), Nuthetal, Germany
| | - Sabine Guth
- Leibniz Research Centre for Working Environment and Human Factors (IfADo), Dortmund, Germany
| | - Thomas Henle
- Chair of Food Chemistry, TU Dresden, Dresden, Germany
| | | | - Hans-Georg Joost
- Department of Experimental Diabetology, German Institute of Human Nutrition (DIfE), Nuthetal, Germany
| | - Doris Marko
- Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Vienna, Austria
| | - Jana Raupbach
- Institute of Food Chemistry, Technische Universität Braunschweig, Braunschweig, Germany
| | - Angelika Roth
- Leibniz Research Centre for Working Environment and Human Factors (IfADo), Dortmund, Germany
| | | | - Angela Mally
- Department of Toxicology, University of Würzburg, Würzburg, Germany
| |
Collapse
|
|
4
|
Mokhtari S, Mahdavi AH, Jafarpour F, Andani MR, Dattilo M, Nasr-Esfahani MH. Taurine, alpha lipoic acid and vitamin B6 ameliorate the reduced developmental competence of immature mouse oocytes exposed to methylglyoxal. Sci Rep 2024; 14:17937. [PMID: 39095405 PMCID: PMC11297043 DOI: 10.1038/s41598-024-66785-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Accepted: 07/03/2024] [Indexed: 08/04/2024] Open
Abstract
Advanced glycation end products (AGEs) are the final products of the Maillard reaction, formed through the interaction of carbohydrates and proteins. Reactive dicarbonyl compounds such as methylglyoxal (MGO) serve as precursors for AGEs formation. Elevated levels of MGO/AGEs are observed in conditions like obesity, polycystic ovarian syndrome (PCOS), and diabetes, negatively impacting oocyte development. Previous studies have shown that hydrogen sulfide, a gasotransmitter with anti-AGEs effects, is produced in a process influenced by vitamin B6. R-α-lipoic acid (ALA) inhibits protein glycation and AGEs formation while stimulating glutathione (GSH) production. Taurine mitigates oxidative stress and acts as an anti-glycation compound, preventing in vitro glycation and AGEs accumulation. This study aimed to explore the ameliorative effects of a micronutrient support (Taurine, ALA and B6: TAB) on mouse oocytes challenged with MGO. Our results indicate that MGO reduces oocyte developmental competence, while TAB supplementation improves maturation, fertilization, and blastocyst formation rates. TAB also restores cell lineage allocation, redox balance and mitigates mitochondrial dysfunction in MGO-challenged oocytes. Furthermore, cumulus cells express key enzymes in the transsulfuration pathway, and TAB enhances their mRNA expression. However, TAB does not rescue MGO-induced damage in denuded oocytes, emphasizing the supportive role of cumulus cells. Overall, these findings suggest that TAB interventions may have significant implications for addressing reproductive dysfunctions associated with elevated MGO/AGEs levels. This study highlights the potential of TAB supplementation in preserving the developmental competence of COCs exposed to MGO stress, providing insights into mitigating the impact of dicarbonyl stress on oocyte quality and reproductive outcomes.
Collapse
Affiliation(s)
- Saba Mokhtari
- Department of Animal Science, College of Agriculture, Isfahan University of Technology, Isfahan, Iran
| | - Amir Hossein Mahdavi
- Department of Animal Science, College of Agriculture, Isfahan University of Technology, Isfahan, Iran.
| | - Farnoosh Jafarpour
- Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Mohsen Rahimi Andani
- Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | | | - Mohammad Hossein Nasr-Esfahani
- Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
| |
Collapse
|
|
5
|
Wahab M, Janaswamy S. Porous corn starch granules as effective host matrices for encapsulation and sustained release of curcumin and resveratrol. Carbohydr Polym 2024; 333:121967. [PMID: 38494222 DOI: 10.1016/j.carbpol.2024.121967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 02/07/2024] [Accepted: 02/16/2024] [Indexed: 03/19/2024]
Abstract
Type 2 Diabetes Mellitus (T2DM) is a carbohydrate-rich diet-regulated ailment with carbohydrates digested and absorbed rapidly. Hence, modulating carbohydrate digestion is warranted; to this end, polyphenols from plant sources are handy. However, polyphenols' instability and low bioavailability limit their wholesome use, and thus, encapsulating them into an inexpensive and suitable wall material would be the best strategy. Herein, the potential of porous starch granules is demonstrated. Curcumin and resveratrol were chosen as the test polyphenols due to their proven health benefits, and porous corn starch granules were chosen as the wall material. Porous corn starch granules were prepared through enzymatic modification with 11, 22, and 33 units of amyloglucosidase at three reaction times of 2, 4, and 6 h. The polyphenols were loaded at 100, 200, and 500 mg concentrations in 1 g of starch for 21 days and were characterized through Scanning Electron Microscope (SEM) and Fourier Transform Infrared spectroscopy (FTIR) analyses. The encapsulation efficiency was determined, the rate of starch digestion was calculated through the Englyst test, and polyphenols' in vitro release behavior in gastric and intestinal fluids was measured. Results suggest that 33 enzyme units for a 2 h reaction time were optimal for forming spherical-oval pores on corn starch granules with the maximum encapsulation efficiency of 80.16 % and 88.33 % for curcumin and resveratrol, respectively. The FTIR results suggest the entrapment of polyphenols inside the starch matrix. The inclusion significantly reduced starch digestion and increased the percentage of resistant starch up to 41.11 % and 66.36 % with curcumin and resveratrol, respectively. The in vitro release behavior demonstrated good stability in the simulated gastric fluids and sustained release in simulated intestinal fluids. The encapsulated polyphenols showed a complex Fickian type of diffusion mechanism. Overall, the results suggest that porous corn starch granules could be a potential delivery system for curcumin and resveratrol and will aid in developing novel functional foods to address the T2DM concerns.
Collapse
Affiliation(s)
- Maryam Wahab
- Department of Dairy and Food Science, South Dakota State University, Brookings, SD 57007, USA
| | - Srinivas Janaswamy
- Department of Dairy and Food Science, South Dakota State University, Brookings, SD 57007, USA.
| |
Collapse
|
|
6
|
Tshivhase AM, Matsha T, Raghubeer S. The protective role of resveratrol against high glucose-induced oxidative stress and apoptosis in HepG2 cells. Food Sci Nutr 2024; 12:3574-3584. [PMID: 38726423 PMCID: PMC11077230 DOI: 10.1002/fsn3.4027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 12/19/2023] [Accepted: 01/31/2024] [Indexed: 05/12/2024] Open
Abstract
High glucose concentrations result in oxidative stress, leading to damage of cellular constituents like DNA, proteins, and lipids, ultimately resulting in apoptosis. Resveratrol, a polyphenol phytoalexin, has been studied for its potential therapeutic effects on diabetes. This study investigated the influence of high glucose (HG) on HepG2 cells and assessed resveratrol's effect on high-glucose-induced oxidative stress and apoptosis. HepG2 cells were cultured for 48 and 72 h with high glucose (40 mM), low resveratrol (25 μM), high resveratrol (50 μM), high glucose + low resveratrol, and high glucose + high resveratrol. After exposure, oxidative and apoptosis-related gene expression was evaluated using quantitative polymerase chain reaction (qPCR), and lactate dehydrogenase (LDH) release was measured using the supernatant. In HepG2 cells cultured with high glucose, all antioxidant enzymes (SOD, superoxide dismutase; GPx1, glutathione peroxidase 1; CAT, catalase; Nrf2, nuclear factor erythroid 2-related factor 2; and NQO1, NAD(P)H quinone oxidoreductase 1) were significantly reduced; however, when HepG2 cells were cultured with resveratrol (25 and 50 μM) and high glucose, the expression levels of all antioxidant enzymes were increased. The anti-apoptotic gene (B-cell lymphoma 2; Bcl2) and the DNA repair gene (Oxoguanine glycosylase-1, OGG1) were significantly decreased following high glucose exposure to HepG2 cells. Surprisingly, the expression levels of Bcl2 and OGG1 were notably elevated after resveratrol treatment. Furthermore, high glucose levels increased the LHD release in HepG2 cells, whereas resveratrol treatment reduced the LDH release. Our results demonstrate that resveratrol provides protection against oxidative stress and apoptosis induced by high glucose in HepG2 cells. Hence, resveratrol shows potential as an effective approach to address the impaired antioxidant response resulting from elevated glucose levels commonly observed in diabetes and metabolic disorders.
Collapse
Affiliation(s)
- Abegail Mukhethwa Tshivhase
- SAMRC/CPUT Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness SciencesCape Peninsula University of TechnologyBellvilleSouth Africa
| | - Tandi Matsha
- SAMRC/CPUT Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness SciencesCape Peninsula University of TechnologyBellvilleSouth Africa
- Sefako Makgatho Health Sciences UniversityGa‐RankuwaSouth Africa
| | - Shanel Raghubeer
- SAMRC/CPUT Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness SciencesCape Peninsula University of TechnologyBellvilleSouth Africa
| |
Collapse
|
|
7
|
Akhtar A, Singh S, Kaushik R, Awasthi R, Behl T. Types of memory, dementia, Alzheimer's disease, and their various pathological cascades as targets for potential pharmacological drugs. Ageing Res Rev 2024; 96:102289. [PMID: 38582379 DOI: 10.1016/j.arr.2024.102289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 03/30/2024] [Accepted: 03/30/2024] [Indexed: 04/08/2024]
Abstract
Alzheimer's disease (AD) is the most common type of dementia accounting for 90% of cases; however, frontotemporal dementia, vascular dementia, etc. prevails only in a minority of populations. The term dementia is defined as loss of memory which further takes several other categories of memories like working memory, spatial memory, fear memory, and long-term, and short-term memory into consideration. In this review, these memories have critically been elaborated based on context, duration, events, appearance, intensity, etc. The most important part and purpose of the review is the various pathological cascades as well as molecular levels of targets of AD, which have extracellular amyloid plaques and intracellular hyperphosphorylated tau protein as major disease hallmarks. There is another phenomenon that either leads to or arises from the above-mentioned hallmarks, such as oxidative stress, mitochondrial dysfunction, neuroinflammation, cholinergic dysfunction, and insulin resistance. Several potential drugs like antioxidants, anti-inflammatory drugs, acetylcholinesterase inhibitors, insulin mimetics or sensitizers, etc. studied in various previous preclinical or clinical reports were put as having the capacity to act on these pathological targets. Additionally, agents directly or indirectly targeting amyloid and tau were also discussed. This could be further investigated in future research.
Collapse
Affiliation(s)
- Ansab Akhtar
- Louisiana State University Health Sciences Center, Neuroscience Center of Excellence, School of Medicine, New Orleans, LA 70112, USA.
| | - Siddharth Singh
- School of Health Sciences & Technology, UPES University, Bidholi, Dehradun, Uttarakhand 248007, India
| | - Ravinder Kaushik
- School of Health Sciences & Technology, UPES University, Bidholi, Dehradun, Uttarakhand 248007, India
| | - Rajendra Awasthi
- School of Health Sciences & Technology, UPES University, Bidholi, Dehradun, Uttarakhand 248007, India
| | - Tapan Behl
- Amity School of Pharmaceutical Sciences, Amity University, Mohali, Punjab 140306, India
| |
Collapse
|
|
8
|
Alhujaily M. Molecular Assessment of Methylglyoxal-Induced Toxicity and Therapeutic Approaches in Various Diseases: Exploring the Interplay with the Glyoxalase System. Life (Basel) 2024; 14:263. [PMID: 38398772 PMCID: PMC10890012 DOI: 10.3390/life14020263] [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: 12/16/2023] [Revised: 01/31/2024] [Accepted: 02/07/2024] [Indexed: 02/25/2024] Open
Abstract
This comprehensive exploration delves into the intricate interplay of methylglyoxal (MG) and glyoxalase 1 (GLO I) in various physiological and pathological contexts. The linchpin of the narrative revolves around the role of these small molecules in age-related issues, diabetes, obesity, cardiovascular diseases, and neurodegenerative disorders. Methylglyoxal, a reactive dicarbonyl metabolite, takes center stage, becoming a principal player in the development of AGEs and contributing to cell and tissue dysfunction. The dual facets of GLO I-activation and inhibition-unfold as potential therapeutic avenues. Activators, spanning synthetic drugs like candesartan to natural compounds like polyphenols and isothiocyanates, aim to restore GLO I function. These molecular enhancers showcase promising outcomes in conditions such as diabetic retinopathy, kidney disease, and beyond. On the contrary, GLO I inhibitors emerge as crucial players in cancer treatment, offering new possibilities in diseases associated with inflammation and multidrug resistance. The symphony of small molecules, from GLO I activators to inhibitors, presents a nuanced understanding of MG regulation. From natural compounds to synthetic drugs, each element contributes to a molecular orchestra, promising novel interventions and personalized approaches in the pursuit of health and wellbeing. The abstract concludes with an emphasis on the necessity of rigorous clinical trials to validate these findings and acknowledges the importance of individual variability in the complex landscape of health.
Collapse
Affiliation(s)
- Muhanad Alhujaily
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha, Bisha 61922, Saudi Arabia
| |
Collapse
|
|
9
|
Han X, Wang H, Du F, Zeng X, Guo C. Nrf2 for a key member of redox regulation: A novel insight against myocardial ischemia and reperfusion injuries. Biomed Pharmacother 2023; 168:115855. [PMID: 37939614 DOI: 10.1016/j.biopha.2023.115855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 10/21/2023] [Accepted: 11/05/2023] [Indexed: 11/10/2023] Open
Abstract
Nuclear factor erythroid-2 related factor 2 (Nrf2), a nuclear transcription factor, modulates genes responsible for antioxidant responses against toxic and oxidative stress to maintain redox homeostasis and participates in varieties of cellular processes such as metabolism and inflammation during myocardial ischemia and reperfusion injuries (MIRI). The accumulation of reactive oxygen species (ROS) from damaged mitochondria, xanthine oxidase, NADPH oxidases, and inflammation contributes to depraved myocardial ischemia and reperfusion injuries. Considering that Nrf2 played crucial roles in antagonizing oxidative stress, it is reasonable to delve into the up or down-regulated molecular mechanisms of Nrf2 in the progression of MIRI to provide the possibility of new therapeutic medicine targeting Nrf2 in cardiovascular diseases. This review systematically describes the generation of ROS, the regulatory metabolisms of Nrf2 as well as several natural or synthetic compounds activating Nrf2 during MIRI, which might provide novel insights for the anti-oxidative stress and original ideas targeting Nrf2 for the prevention and treatment in cardiovascular diseases.
Collapse
Affiliation(s)
- Xuejie Han
- Cardiovascular Center, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaomin Lane, Dongcheng District, Beijing 100730, PR China
| | - Hongxia Wang
- Department of Physiology and Pathophysiology, Capital Medical University, No. 10 You An Men Wai Xi Tou Tiao, Fengtai District, Beijing 100069, PR China
| | - Fenghe Du
- Department of Geriatrics, Beijing Tiantan Hospital, Capital Medical University, No. 119 South 4th Ring West Road, Fengtai District, Beijing 100070, PR China
| | - Xiangjun Zeng
- Department of Physiology and Pathophysiology, Capital Medical University, No. 10 You An Men Wai Xi Tou Tiao, Fengtai District, Beijing 100069, PR China.
| | - Caixia Guo
- Cardiovascular Center, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaomin Lane, Dongcheng District, Beijing 100730, PR China.
| |
Collapse
|
|
10
|
Wang W, Yang W, Dai Y, Liu J, Chen ZY. Production of Food-Derived Bioactive Peptides with Potential Application in the Management of Diabetes and Obesity: A Review. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:5917-5943. [PMID: 37027889 PMCID: PMC11966776 DOI: 10.1021/acs.jafc.2c08835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 03/12/2023] [Accepted: 03/14/2023] [Indexed: 06/19/2023]
Abstract
The prevalence of diabetes mellitus and obesity is increasing worldwide. Bioactive peptides are naturally present in foods or in food-derived proteins. Recent research has shown that these bioactive peptides have an array of possible health benefits in the management of diabetes and obesity. First, this review will summarize the top-down and bottom-up production methods of the bioactive peptides from different protein sources. Second, the digestibility, bioavailability, and metabolic fate of the bioactive peptides are discussed. Last, the present review will discuss and explore the mechanisms by which these bioactive peptides help against obesity and diabetes based on in vitro and in vivo studies. Although several clinical studies have demonstrated that bioactive peptides are beneficial in alleviating diabetes and obesity, more double-blind randomized controlled trials are needed in the future. This review has provided novel insights into the potential of food-derived bioactive peptides as functional foods or nutraceuticals to manage obesity and diabetes.
Collapse
Affiliation(s)
- Weiwei Wang
- College
of Food Science and Engineering, Nanjing
University of Finance and Economics/Collaborative Innovation Center
for Modern Grain Circulation and Safety, Nanjing 210023, China
| | - Wenjian Yang
- College
of Food Science and Engineering, Nanjing
University of Finance and Economics/Collaborative Innovation Center
for Modern Grain Circulation and Safety, Nanjing 210023, China
| | - Yi Dai
- College
of Food Science and Engineering, Nanjing
University of Finance and Economics/Collaborative Innovation Center
for Modern Grain Circulation and Safety, Nanjing 210023, China
| | - Jianhui Liu
- College
of Food Science and Engineering, Nanjing
University of Finance and Economics/Collaborative Innovation Center
for Modern Grain Circulation and Safety, Nanjing 210023, China
| | - Zhen-Yu Chen
- Food
& Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China
| |
Collapse
|
|
11
|
Meng Q, Li J, Wang C, Shan A. Biological function of resveratrol and its application in animal production: a review. J Anim Sci Biotechnol 2023; 14:25. [PMID: 36765425 PMCID: PMC9921422 DOI: 10.1186/s40104-022-00822-z] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 12/08/2022] [Indexed: 02/12/2023] Open
Abstract
With the prohibition of antibiotics in feed, plant functional substances have been widely studied as feed additives. Resveratrol, a natural stilbene, and a non-flavonoid polyphenol found in plants, possesses antioxidant, anti-inflammatory, and metabolic regulatory features. Resveratrol generated intense scientific and public interest, primarily due to its widely reported ability to prevent cancer, delay aging and alleviate related metabolic diseases. Recently, resveratrol has been studied and applied as a feed additive in animal production. This review focuses on the outline of the absorption and metabolism and biological functions of resveratrol and summarizes the application of dietary resveratrol in animal production up to the present, including pigs, poultry, and ruminants. In pigs, dietary resveratrol improved intestinal health, mitochondrial function, meat quality, and more. In poultry, studies have shown that dietary resveratrol improves growth performance and meat and egg quality and alleviates heat stress induced adverse effects. There are few studies on dietary resveratrol in ruminants; however previous studies have indicated that dietary resveratrol increases nutrient digestibility and reduces methane emissions in sheep. It is hoped that this review could provide a specific theoretical basis and research ideas for the research and application of resveratrol.
Collapse
Affiliation(s)
- Qingwei Meng
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, China
| | - Jiawei Li
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, China
| | - Chunsheng Wang
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, China
| | - Anshan Shan
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, China.
| |
Collapse
|
|
12
|
Coelho OGL, Ribeiro PVM, Alfenas RDCG. Can grape polyphenols affect glycation markers? A systematic review. Crit Rev Food Sci Nutr 2023; 63:1208-1218. [PMID: 34369228 DOI: 10.1080/10408398.2021.1962796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Advanced glycation end-products (AGEs) favor inflammation and oxidative stress, playing a role in chronic diseases pathogenesis. Grape polyphenols exert antiglycative and antioxidant effects which may contribute to prevent chronic diseases. However, clinical evidence of grape polyphenols on chronic disease prevention and treatment by glycation markers modulation are limited. Therefore, we aimed to critically analyze studies about that topic to investigate the antiglycative power of dietary grape polyphenol, and to explore the molecular mechanism involved. This systematic review was conducted and reported according to PRISMA guidelines. The following search terms were used: "grape", "extract", "grape seed extract", "grape skin extract", "polyphenol extract", "grape polyphenol(s)", "grape juice", "resveratrol", "quercetin", "catechin", "epicatechin", "procyanidin(s)", and "anthocyanin(s)". Seven studies were included. Glycated hemoglobin was not affected. The interventions duration may not have been enough to detect changes. Grape polyphenols reduced fructosamine and methylglyoxal (MGO) concentrations, and increased endogenous secretory RAGE (esRAGE) gene expression but did not affect the serum concentration. Resveratrol antiglycative effects are mainly due its ability to trap MGO and downregulate RAGE. In conclusion, grape polyphenols may have a positive impact on early glycation products, AGEs and esRAGE. Future studies are needed to explore how they modulate AGEs and receptors in chronic diseases.
Collapse
Affiliation(s)
- Olívia G L Coelho
- Departamento de Nutrição de Saúde, Universidade Federal de Viçosa, Viçosa, Brazil
| | - Priscila V M Ribeiro
- Departamento de Nutrição de Saúde, Universidade Federal de Viçosa, Viçosa, Brazil
| | | |
Collapse
|
|
13
|
Zhou Q, Zhang N, Hu T, Xu H, Duan X, Liu B, Chen F, Wang M. Dietary phenolic-type Nrf2-activators: implications in the control of toxin-induced hepatic disorders. Food Funct 2022; 13:5480-5497. [PMID: 35411358 DOI: 10.1039/d1fo04237h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Numerous studies have exemplified the importance of nuclear factor erythroid 2-related factor 2 (Nrf2) activation in the alleviation of toxin-induced hepatic disorders primarily through eliminating oxidative stress. Whereafter, increasingly more efforts have been contributed to finding Nrf2-activators, especially from dietary polyphenols. The present review summarized the phenolic-type Nrf2-activators published in the past few decades, analyzed their effectiveness based on their structural characteristics and outlined their related mechanisms. It turns out that flavonoids are the largest group of phenolic-type Nrf2-activators, followed by nonflavonoids and phenolic acids. When counting on subgroups, the top three types are flavonols, flavones, and hydroxycinnamic acids, with curcuminoids having the highest effective doses. Moreover, most polyphenols work through the phosphorylation of Nrf2. Besides, mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt) are the frequent targets of these Nrf2-activators, which indirectly mediate the behavior of Nrf2. However, current data are not sufficient to conclude any structure-activity relationship.
Collapse
Affiliation(s)
- Qian Zhou
- Institute for Advanced Study, Shenzhen University, Shenzhen, China. .,Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, China.
| | - Nana Zhang
- School of Biological Sciences, The University of Hong Kong, Hong Kong, China
| | - Tingyan Hu
- Institute for Advanced Study, Shenzhen University, Shenzhen, China. .,Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, China.
| | - Hui Xu
- Institute for Advanced Study, Shenzhen University, Shenzhen, China. .,Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, China.
| | - Xinxing Duan
- Schlegel Research Institute for Aging & Department of Electrical and Computer Engineering, University of Waterloo, Waterloo, Canada
| | - Bin Liu
- Institute for Advanced Study, Shenzhen University, Shenzhen, China. .,Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, China.
| | - Feng Chen
- Institute for Advanced Study, Shenzhen University, Shenzhen, China. .,Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, China.
| | - Mingfu Wang
- Institute for Advanced Study, Shenzhen University, Shenzhen, China. .,Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, China.
| |
Collapse
|
|
14
|
Rampin A, Carrabba M, Mutoli M, Eman CL, Testa G, Madeddu P, Spinetti G. Recent Advances in KEAP1/NRF2-Targeting Strategies by Phytochemical Antioxidants, Nanoparticles, and Biocompatible Scaffolds for the Treatment of Diabetic Cardiovascular Complications. Antioxid Redox Signal 2022; 36:707-728. [PMID: 35044251 DOI: 10.1089/ars.2021.0134] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Significance: Modulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated antioxidant response is a key aspect in the onset of diabetes-related cardiovascular complications. With this review, we provide an overview of the recent advances made in the development of Nrf2-targeting strategies for the treatment of diabetes, with particular attention toward the activation of Nrf2 by natural antioxidant compounds, nanoparticles, and oxidative stress-modulating biocompatible scaffolds. Recent Advances: In the past 30 years, studies addressing the use of antioxidant therapies to treat diabetes have grown exponentially, showing promising but yet inconclusive results. Animal studies and clinical trials on the Nrf2 pathway have shown promising results, suggesting that its activation can delay or reverse some of the cardiovascular impairments in diabetes. Critical Issues: Hyperglycemia- and oscillating glucose levels-induced reactive oxygen species (ROS) accumulation is progressively emerging as a central factor in the onset and progression of diabetes-related cardiovascular complications, including endothelial dysfunction, retinopathy, heart failure, stroke, critical limb ischemia, ulcers, and delayed wound healing. In this context, accumulating evidence suggests a central role for Nrf2-mediated antioxidant response, one of the most studied cellular defensive mechanisms against ROS accumulation. Future Directions: Innovative approaches such as tissue engineering and nanotechnology are converging toward targeting oxidative stress in diabetes. Antioxid. Redox Signal. 36, 707-728.
Collapse
Affiliation(s)
- Andrea Rampin
- Laboratory of Cardiovascular Physiopathology-Regenerative Medicine, IRCCS MultiMedica, Milan, Italy
| | - Michele Carrabba
- Laboratory of Experimental Cardiovascular Medicine, University of Bristol, Bristol, England, United Kingdom
| | - Martina Mutoli
- Laboratory of Cardiovascular Physiopathology-Regenerative Medicine, IRCCS MultiMedica, Milan, Italy
| | - Charlotte L Eman
- Laboratory of Cardiovascular Physiopathology-Regenerative Medicine, IRCCS MultiMedica, Milan, Italy
| | - Gianluca Testa
- Department of Medicine and Health Sciences, "V. Tiberio" University of Molise, Campobasso, Italy.,Interdepartmental Center for Nanotechnology Research-NanoBem, University of Molise, Campobasso, Italy
| | - Paolo Madeddu
- Laboratory of Experimental Cardiovascular Medicine, University of Bristol, Bristol, England, United Kingdom
| | - Gaia Spinetti
- Laboratory of Cardiovascular Physiopathology-Regenerative Medicine, IRCCS MultiMedica, Milan, Italy
| |
Collapse
|
|
15
|
Thouvenot K, Turpin T, Taïlé J, Clément K, Meilhac O, Gonthier MP. Links between Insulin Resistance and Periodontal Bacteria: Insights on Molecular Players and Therapeutic Potential of Polyphenols. Biomolecules 2022; 12:biom12030378. [PMID: 35327570 PMCID: PMC8945445 DOI: 10.3390/biom12030378] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 02/22/2022] [Accepted: 02/24/2022] [Indexed: 02/07/2023] Open
Abstract
Type 2 diabetes is a metabolic disease mainly associated with insulin resistance during obesity and constitutes a major public health problem worldwide. A strong link has been established between type 2 diabetes and periodontitis, an infectious dental disease characterized by chronic inflammation and destruction of the tooth-supporting tissue or periodontium. However, the molecular mechanisms linking periodontal bacteria and insulin resistance remain poorly elucidated. This study aims to summarize the mechanisms possibly involved based on in vivo and in vitro studies and targets them for innovative therapies. Indeed, during periodontitis, inflammatory lesions of the periodontal tissue may allow periodontal bacteria to disseminate into the bloodstream and reach tissues, including adipose tissue and skeletal muscles that store glucose in response to insulin. Locally, periodontal bacteria and their components, such as lipopolysaccharides and gingipains, may deregulate inflammatory pathways, altering the production of pro-inflammatory cytokines/chemokines. Moreover, periodontal bacteria may promote ROS overproduction via downregulation of the enzymatic antioxidant defense system, leading to oxidative stress. Crosstalk between players of inflammation and oxidative stress contributes to disruption of the insulin signaling pathway and promotes insulin resistance. In parallel, periodontal bacteria alter glucose and lipid metabolism in the liver and deregulate insulin production by pancreatic β-cells, contributing to hyperglycemia. Interestingly, therapeutic management of periodontitis reduces systemic inflammation markers and ameliorates insulin sensitivity in type 2 diabetic patients. Of note, plant polyphenols exert anti-inflammatory and antioxidant activities as well as insulin-sensitizing and anti-bacterial actions. Thus, polyphenol-based therapies are of high interest for helping to counteract the deleterious effects of periodontal bacteria and improve insulin resistance.
Collapse
Affiliation(s)
- Katy Thouvenot
- Université de La Réunion, Inserm, UMR 1188 Diabète Athérothrombose Thérapies Réunion Océan Indien (DéTROI), 97490 Saint-Denis de La Réunion, France; (K.T.); (T.T.); (J.T.); (O.M.)
| | - Teva Turpin
- Université de La Réunion, Inserm, UMR 1188 Diabète Athérothrombose Thérapies Réunion Océan Indien (DéTROI), 97490 Saint-Denis de La Réunion, France; (K.T.); (T.T.); (J.T.); (O.M.)
| | - Janice Taïlé
- Université de La Réunion, Inserm, UMR 1188 Diabète Athérothrombose Thérapies Réunion Océan Indien (DéTROI), 97490 Saint-Denis de La Réunion, France; (K.T.); (T.T.); (J.T.); (O.M.)
| | - Karine Clément
- Nutrition and Obesity, Systemic Approaches (NutriOmics), INSERM, Sorbonne Université, 75013 Paris, France
| | - Olivier Meilhac
- Université de La Réunion, Inserm, UMR 1188 Diabète Athérothrombose Thérapies Réunion Océan Indien (DéTROI), 97490 Saint-Denis de La Réunion, France; (K.T.); (T.T.); (J.T.); (O.M.)
| | - Marie-Paule Gonthier
- Université de La Réunion, Inserm, UMR 1188 Diabète Athérothrombose Thérapies Réunion Océan Indien (DéTROI), 97490 Saint-Denis de La Réunion, France; (K.T.); (T.T.); (J.T.); (O.M.)
- Correspondence: ; Tel.: +33-262-693-92-08-55
| |
Collapse
|
|
16
|
Zhou S, Chen J, Fan F, Pan Y, Feng X, Yu L, Gong S, Zheng X, Jiang Y, Chu Q. Apios americana Medik flower extract protects high-glucose-treated hepatocytes and Caenorhabditis elegans. FOOD BIOSCI 2022. [DOI: 10.1016/j.fbio.2021.101473] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
|
|
17
|
Sarmah S, Roy AS. A review on prevention of glycation of proteins: Potential therapeutic substances to mitigate the severity of diabetes complications. Int J Biol Macromol 2022; 195:565-588. [DOI: 10.1016/j.ijbiomac.2021.12.041] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 12/03/2021] [Accepted: 12/05/2021] [Indexed: 12/21/2022]
|
|
18
|
Mata A, Cadenas S. The Antioxidant Transcription Factor Nrf2 in Cardiac Ischemia-Reperfusion Injury. Int J Mol Sci 2021; 22:11939. [PMID: 34769371 PMCID: PMC8585042 DOI: 10.3390/ijms222111939] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 10/27/2021] [Accepted: 10/30/2021] [Indexed: 12/25/2022] Open
Abstract
Nuclear factor erythroid-2 related factor 2 (Nrf2) is a transcription factor that controls cellular defense responses against toxic and oxidative stress by modulating the expression of genes involved in antioxidant response and drug detoxification. In addition to maintaining redox homeostasis, Nrf2 is also involved in various cellular processes including metabolism and inflammation. Nrf2 activity is tightly regulated at the transcriptional, post-transcriptional and post-translational levels, which allows cells to quickly respond to pathological stress. In the present review, we describe the molecular mechanisms underlying the transcriptional regulation of Nrf2. We also focus on the impact of Nrf2 in cardiac ischemia-reperfusion injury, a condition that stimulates the overproduction of reactive oxygen species. Finally, we analyze the protective effect of several natural and synthetic compounds that induce Nrf2 activation and protect against ischemia-reperfusion injury in the heart and other organs, and their potential clinical application.
Collapse
Affiliation(s)
- Ana Mata
- Centro de Biología Molecular “Severo Ochoa” (CSIC/UAM), 28049 Madrid, Spain;
- Instituto de Investigación Sanitaria Princesa (IIS-IP), 28006 Madrid, Spain
| | - Susana Cadenas
- Centro de Biología Molecular “Severo Ochoa” (CSIC/UAM), 28049 Madrid, Spain;
- Instituto de Investigación Sanitaria Princesa (IIS-IP), 28006 Madrid, Spain
| |
Collapse
|
|
19
|
Lin H, Lin TY, Lin JA, Cheng KC, Santoso SP, Chou CH, Hsieh CW. Effect of Pholiota nameko Polysaccharides Inhibiting Methylglyoxal-Induced Glycation Damage In Vitro. Antioxidants (Basel) 2021; 10:antiox10101589. [PMID: 34679724 PMCID: PMC8533542 DOI: 10.3390/antiox10101589] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 10/05/2021] [Accepted: 10/07/2021] [Indexed: 02/01/2023] Open
Abstract
Advanced glycation end products (AGEs) can induce oxidative stress and inflammation. AGEs are major risk factors for the development of many aging-related diseases, such as cancer and diabetes. In this study, Pholiota nameko polysaccharides (PNPs) were prepared from water extract of P. nameko via graded alcohol precipitation (40%, 60%, and 80% v/v). We explored the in vitro antiglycation ability of the PNPs and inhibition of methylglyoxal (MG)-induced Hs68 cell damage. In a bovine serum albumin (BSA) glycation system, PNPs significantly inhibited the formation of Amadori products. Fluorescence spectrophotometry revealed that the PNPs trapped MG and reduced MG-induced changes in functional groups (carbonyl and ε-NH2) in the BSA. Pretreating Hs68 cells with PNPs enhanced the cell survival rate and protected against MG-induced cell damage. This was due to decreased intracellular ROS content. PNPs thus mitigate skin cell damage and oxidative stress resulting from glycation stress, making them a potential raw material for antiaging-related skincare products.
Collapse
Affiliation(s)
- His Lin
- Department of Food Science and Biotechnology, National Chung Hsing University, 145 Xingda Rd., South Dist., Taichung City 40227, Taiwan; (H.L.); (T.-Y.L.)
| | - Ting-Yun Lin
- Department of Food Science and Biotechnology, National Chung Hsing University, 145 Xingda Rd., South Dist., Taichung City 40227, Taiwan; (H.L.); (T.-Y.L.)
| | - Jer-An Lin
- Graduate Institute of Food Safety, National Chung Hsing University, 145 Xingda Rd., South Dist., Taichung City 40227, Taiwan;
| | - Kuan-Chen Cheng
- Institute of Biotechnology, National Taiwan University, Taipei 10617, Taiwan;
- Graduate Institute of Food Science Technology, National Taiwan University, Taipei 10617, Taiwan
- Department of Optometry, Asia University, 500, Lioufeng Rd., Wufeng, Taichung City 41354, Taiwan
- Department of Medical Research, China Medical University Hospital, Taichung City 406040, Taiwan
| | - Shella Permatasari Santoso
- Department of Chemical Engineering, Widya Mandala Surabaya Catholic University, Kalijudan 37, Surabaya 60114, Indonesia;
- Department of Chemical Engineering, National Taiwan University of Science and Technology, Keelung Rd. 43, Da’an Dist., Taipei 10607, Taiwan
| | - Chun-Hsu Chou
- Dr Jou Biotech Co., Ltd., No. 21, Lugong S. 2nd Rd., Lukang Township, Changhua 505, Taiwan;
| | - Chang-Wei Hsieh
- Department of Food Science and Biotechnology, National Chung Hsing University, 145 Xingda Rd., South Dist., Taichung City 40227, Taiwan; (H.L.); (T.-Y.L.)
- Department of Medical Research, China Medical University Hospital, Taichung City 406040, Taiwan
- Correspondence: ; Tel.: +886-4-2284-0385 (ext. 5031); Fax: +886-4-2287-6211
| |
Collapse
|
|
20
|
Rodríguez ML, Millán I, Ortega ÁL. Cellular targets in diabetic retinopathy therapy. World J Diabetes 2021; 12:1442-1462. [PMID: 34630899 PMCID: PMC8472497 DOI: 10.4239/wjd.v12.i9.1442] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 05/08/2021] [Accepted: 08/03/2021] [Indexed: 02/06/2023] Open
Abstract
Despite the existence of treatment for diabetes, inadequate metabolic control triggers the appearance of chronic complications such as diabetic retinopathy. Diabetic retinopathy is considered a multifactorial disease of complex etiology in which oxidative stress and low chronic inflammation play essential roles. Chronic exposure to hyperglycemia triggers a loss of redox balance that is critical for the appearance of neuronal and vascular damage during the development and progression of the disease. Current therapies for the treatment of diabetic retinopathy are used in advanced stages of the disease and are unable to reverse the retinal damage induced by hyperglycemia. The lack of effective therapies without side effects means there is an urgent need to identify an early action capable of preventing the development of the disease and its pathophysiological consequences in order to avoid loss of vision associated with diabetic retinopathy. Therefore, in this review we propose different therapeutic targets related to the modulation of the redox and inflammatory status that, potentially, can prevent the development and progression of the disease.
Collapse
Affiliation(s)
- María Lucía Rodríguez
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Burjassot 46100, Valencia, Spain
| | - Iván Millán
- Neonatal Research Group, Health Research Institute La Fe, Valencia 46026, Valencia, Spain
| | - Ángel Luis Ortega
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Burjassot 46100, Valencia, Spain
| |
Collapse
|
|
21
|
The Glyoxalase System in Age-Related Diseases: Nutritional Intervention as Anti-Ageing Strategy. Cells 2021; 10:cells10081852. [PMID: 34440621 PMCID: PMC8393707 DOI: 10.3390/cells10081852] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 07/09/2021] [Accepted: 07/15/2021] [Indexed: 12/19/2022] Open
Abstract
The glyoxalase system is critical for the detoxification of advanced glycation end-products (AGEs). AGEs are toxic compounds resulting from the non-enzymatic modification of biomolecules by sugars or their metabolites through a process called glycation. AGEs have adverse effects on many tissues, playing a pathogenic role in the progression of molecular and cellular aging. Due to the age-related decline in different anti-AGE mechanisms, including detoxifying mechanisms and proteolytic capacities, glycated biomolecules are accumulated during normal aging in our body in a tissue-dependent manner. Viewed in this way, anti-AGE detoxifying systems are proposed as therapeutic targets to fight pathological dysfunction associated with AGE accumulation and cytotoxicity. Here, we summarize the current state of knowledge related to the protective mechanisms against glycative stress, with a special emphasis on the glyoxalase system as the primary mechanism for detoxifying the reactive intermediates of glycation. This review focuses on glyoxalase 1 (GLO1), the first enzyme of the glyoxalase system, and the rate-limiting enzyme of this catalytic process. Although GLO1 is ubiquitously expressed, protein levels and activities are regulated in a tissue-dependent manner. We provide a comparative analysis of GLO1 protein in different tissues. Our findings indicate a role for the glyoxalase system in homeostasis in the eye retina, a highly oxygenated tissue with rapid protein turnover. We also describe modulation of the glyoxalase system as a therapeutic target to delay the development of age-related diseases and summarize the literature that describes the current knowledge about nutritional compounds with properties to modulate the glyoxalase system.
Collapse
|
|
22
|
Byrne NJ, Rajasekaran NS, Abel ED, Bugger H. Therapeutic potential of targeting oxidative stress in diabetic cardiomyopathy. Free Radic Biol Med 2021; 169:317-342. [PMID: 33910093 PMCID: PMC8285002 DOI: 10.1016/j.freeradbiomed.2021.03.046] [Citation(s) in RCA: 91] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 02/24/2021] [Accepted: 03/25/2021] [Indexed: 02/07/2023]
Abstract
Even in the absence of coronary artery disease and hypertension, diabetes mellitus (DM) may increase the risk for heart failure development. This risk evolves from functional and structural alterations induced by diabetes in the heart, a cardiac entity termed diabetic cardiomyopathy (DbCM). Oxidative stress, defined as the imbalance of reactive oxygen species (ROS) has been increasingly proposed to contribute to the development of DbCM. There are several sources of ROS production including the mitochondria, NAD(P)H oxidase, xanthine oxidase, and uncoupled nitric oxide synthase. Overproduction of ROS in DbCM is thought to be counterbalanced by elevated antioxidant defense enzymes such as catalase and superoxide dismutase. Excess ROS in the cardiomyocyte results in further ROS production, mitochondrial DNA damage, lipid peroxidation, post-translational modifications of proteins and ultimately cell death and cardiac dysfunction. Furthermore, ROS modulates transcription factors responsible for expression of antioxidant enzymes. Lastly, evidence exists that several pharmacological agents may convey cardiovascular benefit by antioxidant mechanisms. As such, increasing our understanding of the pathways that lead to increased ROS production and impaired antioxidant defense may enable the development of therapeutic strategies against the progression of DbCM. Herein, we review the current knowledge about causes and consequences of ROS in DbCM, as well as the therapeutic potential and strategies of targeting oxidative stress in the diabetic heart.
Collapse
Affiliation(s)
- Nikole J Byrne
- Division of Cardiology, Medical University of Graz, Graz, Austria
| | - Namakkal S Rajasekaran
- Cardiac Aging & Redox Signaling Laboratory, Molecular and Cellular Pathology, Department of Pathology, Birmingham, AL, USA; Division of Cardiovascular Medicine, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA; Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - E Dale Abel
- Fraternal Order of Eagles Diabetes Research Center, Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, USA
| | - Heiko Bugger
- Division of Cardiology, Medical University of Graz, Graz, Austria.
| |
Collapse
|
|
23
|
Shyur LF, Varga V, Chen CM, Mu SC, Chang YC, Li SC. Extract of white sweet potato tuber against TNF-α-induced insulin resistance by activating the PI3K/Akt pathway in C2C12 myotubes. BOTANICAL STUDIES 2021; 62:7. [PMID: 34003397 PMCID: PMC8131422 DOI: 10.1186/s40529-021-00315-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Accepted: 05/11/2021] [Indexed: 06/12/2023]
Abstract
BACKGROUND White sweet potato (WSP; Ipomoea batatas L. Simon No. 1) has many potential beneficial effects on metabolic control and diabetes-related insulin resistance. The improvement of insulin resistance by WSP tuber extracts on glucose uptake were not investigated in C2C12 myoblast cells. RESULTS WSP tuberous ethanol extract (WSP-E) was partitioned with ethyl-acetate and water to obtain ethyl-acetate layer (WSP-EA) and water layer (WSP-EW). The WSP-EA shows the highest total phenolic contents and highest antioxidant activity by Folin-Ciocalteu and (2,2-diphenyl-1-picryl-hydrazyl-hydrate, DPPH) assay, respectively. After low concentration horse serum on differentiation inducement of C2C12 myoblasts into mature myotubes, the cells were treated with TNF-α to induce insulin resistance. WSP-EA and WSP-EW extracts increased the uptake of fluorescence glucose analogue (2-[N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino]-2-deoxy-D-glucose, 2-NBDG) in a dose-dependent manner as examined by flow cytometry. The WSP-EA enhanced glucose uptake by activation of phosphorylation of IR (pIR), IRS-1 (pIRS-1) and Akt (pAkt) involved in PI3K (phosphatidylinositol 3-kinase)/protein kinase B (Akt) pathway, also upregulated glucose transporter 4 (GLUT4) expression in myotubes. CONCLUSIONS WSP-EA enhanced the glucose uptake in C2C12 myotubes through upregulating the PI3K/Akt pathway. The in vitro data reveal that WSP tuber extracts has potential applications to improve insulin resistance in diabetes.
Collapse
Affiliation(s)
- Lie-Fen Shyur
- Agricultural Biotechnology Research Center, Academia Sinica, Taipei, 11529 Taiwan
| | - Viola Varga
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 11031 Taiwan
- Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary
| | - Chiao-Ming Chen
- Department of Food Science, Nutrition, and Nutraceutical Biotechnology, Shih Chien University, Taipei, 10462 Taiwan
| | - Shu-Chi Mu
- School of Medicine, Fu-Jen Catholic University, New Taipei City, 24205 Taiwan
| | - Yu-Chih Chang
- Agricultural Biotechnology Research Center, Academia Sinica, Taipei, 115 Taiwan
| | - Sing-Chung Li
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 11031 Taiwan
| |
Collapse
|
|
24
|
Medrano-Padial C, Puerto M, Richard T, Cantos-Villar E, Pichardo S. Protection and reversion role of a pure stilbene extract from grapevine shoot and its major compounds against an induced oxidative stress. J Funct Foods 2021. [DOI: 10.1016/j.jff.2021.104393] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
|
|
25
|
Wang X, Li Q, Han X, Gong M, Yu Z, Xu B. Electroacupuncture Alleviates Diabetic Peripheral Neuropathy by Regulating Glycolipid-Related GLO/AGEs/RAGE Axis. Front Endocrinol (Lausanne) 2021; 12:655591. [PMID: 34295304 PMCID: PMC8290521 DOI: 10.3389/fendo.2021.655591] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 05/19/2021] [Indexed: 01/04/2023] Open
Abstract
Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus (DM) and affects over one-third of all patients. Neuropathic pain and nerve dysfunction induced by DM is related to the increase of advanced glycation end products (AGEs) produced by reactive dicarbonyl compounds in a hyperglycemia environment. AGEs induce the expression of pro-inflammatory cytokines via the main receptor (RAGE), which has been documented to play a crucial role in the pathogenesis of diabetic peripheral neuropathy. Electroacupuncture (EA) has been reported to have a positive effect on paralgesia caused by various diseases, but the mechanism is unclear. In this study, we used high-fat-fed low-dose streptozotocin-induced rats as a model of type 2 diabetes (T2DM). Persistent metabolic disorder led to mechanical and thermal hyperalgesia, as well as intraepidermal nerve fiber density reduction and nerve demyelination. EA improved neurological hyperalgesia, decreased the pro-inflammatory cytokines, reduced the generation of AGEs and RAGE, and regulated the glyoxalase system in the EA group. Taken together, our study suggested that EA plays a role in the treatment of T2DM-induced DPN, and is probably related to the regulation of metabolism and the secondary influence on the GLO/AGE/RAGE axis.
Collapse
Affiliation(s)
| | | | | | | | - Zhi Yu
- *Correspondence: Zhi Yu, ; Bin Xu,
| | - Bin Xu
- *Correspondence: Zhi Yu, ; Bin Xu,
| |
Collapse
|
|
26
|
Stec DE, Hinds TD. Natural Product Heme Oxygenase Inducers as Treatment for Nonalcoholic Fatty Liver Disease. Int J Mol Sci 2020; 21:E9493. [PMID: 33327438 PMCID: PMC7764878 DOI: 10.3390/ijms21249493] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 12/07/2020] [Accepted: 12/09/2020] [Indexed: 02/06/2023] Open
Abstract
Heme oxygenase (HO) is a critical component of the defense mechanism to a wide variety of cellular stressors. HO induction affords cellular protection through the breakdown of toxic heme into metabolites, helping preserve cellular integrity. Nonalcoholic fatty liver disease (NAFLD) is a pathological condition by which the liver accumulates fat. The incidence of NAFLD has reached all-time high levels driven primarily by the obesity epidemic. NALFD can progress to nonalcoholic steatohepatitis (NASH), advancing further to liver cirrhosis or cancer. NAFLD is also a contributing factor to cardiovascular and metabolic diseases. There are currently no drugs to specifically treat NAFLD, with most treatments focused on lifestyle modifications. One emerging area for NAFLD treatment is the use of dietary supplements such as curcumin, pomegranate seed oil, milk thistle oil, cold-pressed Nigella Satvia oil, and resveratrol, among others. Recent studies have demonstrated that several of these natural dietary supplements attenuate hepatic lipid accumulation and fibrosis in NAFLD animal models. The beneficial actions of several of these compounds are associated with the induction of heme oxygenase-1 (HO-1). Thus, targeting HO-1 through dietary-supplements may be a useful therapeutic for NAFLD either alone or with lifestyle modifications.
Collapse
Affiliation(s)
- David E. Stec
- Department of Physiology & Biophysics, Center for Cardiovascular and Metabolic Diseases Research, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA
| | - Terry D. Hinds
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, 760 Press Avenue, Healthy Kentucky Research Building, Lexington, KY 40508, USA
| |
Collapse
|
|
27
|
He Y, Zhou C, Huang M, Tang C, Liu X, Yue Y, Diao Q, Zheng Z, Liu D. Glyoxalase system: A systematic review of its biological activity, related-diseases, screening methods and small molecule regulators. Biomed Pharmacother 2020; 131:110663. [DOI: 10.1016/j.biopha.2020.110663] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 08/18/2020] [Accepted: 08/20/2020] [Indexed: 12/27/2022] Open
|
|
28
|
Aragonès G, Rowan S, G Francisco S, Yang W, Weinberg J, Taylor A, Bejarano E. Glyoxalase System as a Therapeutic Target against Diabetic Retinopathy. Antioxidants (Basel) 2020; 9:antiox9111062. [PMID: 33143048 PMCID: PMC7692619 DOI: 10.3390/antiox9111062] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 10/25/2020] [Accepted: 10/27/2020] [Indexed: 12/14/2022] Open
Abstract
Hyperglycemia, a defining characteristic of diabetes, combined with oxidative stress, results in the formation of advanced glycation end products (AGEs). AGEs are toxic compounds that have adverse effects on many tissues including the retina and lens. AGEs promote the formation of reactive oxygen species (ROS), which, in turn, boost the production of AGEs, resulting in positive feedback loops, a vicious cycle that compromises tissue fitness. Oxidative stress and the accumulation of AGEs are etiologically associated with the pathogenesis of multiple diseases including diabetic retinopathy (DR). DR is a devastating microvascular complication of diabetes mellitus and the leading cause of blindness in working-age adults. The onset and development of DR is multifactorial. Lowering AGEs accumulation may represent a potential therapeutic approach to slow this sight-threatening diabetic complication. To set DR in a physiological context, in this review we first describe relations between oxidative stress, formation of AGEs, and aging in several tissues of the eye, each of which is associated with a major age-related eye pathology. We summarize mechanisms of AGEs generation and anti-AGEs detoxifying systems. We specifically feature the potential of the glyoxalase system in the retina in the prevention of AGEs-associated damage linked to DR. We provide a comparative analysis of glyoxalase activity in different tissues from wild-type mice, supporting a major role for the glyoxalase system in the detoxification of AGEs in the retina, and present the manipulation of this system as a therapeutic strategy to prevent the onset of DR.
Collapse
Affiliation(s)
- Gemma Aragonès
- Laboratory for Nutrition and Vision Research, USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02155, USA; (G.A.); (S.R.); (S.G.F.); (W.Y.); (J.W.)
| | - Sheldon Rowan
- Laboratory for Nutrition and Vision Research, USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02155, USA; (G.A.); (S.R.); (S.G.F.); (W.Y.); (J.W.)
- Department of Ophthalmology, Tufts University School of Medicine, Boston, MA 02155, USA
- Friedman School of Nutrition and Science Policy, Tufts University, Boston, MA 02155, USA
| | - Sarah G Francisco
- Laboratory for Nutrition and Vision Research, USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02155, USA; (G.A.); (S.R.); (S.G.F.); (W.Y.); (J.W.)
| | - Wenxin Yang
- Laboratory for Nutrition and Vision Research, USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02155, USA; (G.A.); (S.R.); (S.G.F.); (W.Y.); (J.W.)
| | - Jasper Weinberg
- Laboratory for Nutrition and Vision Research, USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02155, USA; (G.A.); (S.R.); (S.G.F.); (W.Y.); (J.W.)
| | - Allen Taylor
- Laboratory for Nutrition and Vision Research, USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02155, USA; (G.A.); (S.R.); (S.G.F.); (W.Y.); (J.W.)
- Department of Ophthalmology, Tufts University School of Medicine, Boston, MA 02155, USA
- Friedman School of Nutrition and Science Policy, Tufts University, Boston, MA 02155, USA
- Correspondence: (A.T.); (E.B.); Tel.: +617-556-3156 (A.T.)
| | - Eloy Bejarano
- Laboratory for Nutrition and Vision Research, USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02155, USA; (G.A.); (S.R.); (S.G.F.); (W.Y.); (J.W.)
- Universidad Cardenal Herrera-CEU, CEU Universities, 46115 Valencia, Spain
- Correspondence: (A.T.); (E.B.); Tel.: +617-556-3156 (A.T.)
| |
Collapse
|
|
29
|
Involvement of HO-1 and Autophagy in the Protective Effect of Magnolol in Hepatic Steatosis-Induced NLRP3 Inflammasome Activation In Vivo and In Vitro. Antioxidants (Basel) 2020; 9:antiox9100924. [PMID: 32992548 PMCID: PMC7600324 DOI: 10.3390/antiox9100924] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 09/24/2020] [Accepted: 09/25/2020] [Indexed: 02/08/2023] Open
Abstract
Magnolol (MG) is the main active compound of Magnolia officinalis and exerts a wide range of biological activities. In this study, we investigated the effects of MG using tyloxapol (Tylo)-induced (200 mg/kg, i.p.) hyperlipidemia in rats and palmitic acid (PA)-stimulated (0.3 mM) HepG2 cells. Our results showed that Tylo injection significantly increased plasma levels of triglyceride and cholesterol as well as superoxide anion in the livers, whereas MG pretreatment reversed these changes. MG reduced hepatic lipogenesis by attenuating sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) proteins and Srebp-1, Fas, Acc, and Cd36 mRNA expression as well as upregulated the lipolysis-associated genes Hsl, Mgl, and Atgl. Furthermore, MG reduced plasma interleukin-1β (IL-1β) and protein expression of NLR family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and caspase 1 as well as upregulated nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and induction of heme oxygenase-1 (HO-1) in hepatocytes of Tylo-treated rats. Enhanced autophagic flux by elevation of autophagy related protein 5-12 (ATG5-12), ATG7, Beclin1, and microtubule-associated protein light chain 3 B II (LC3BII)/LC3BI ratio, and reduction of sequestosome-1 (SQSTM1/p62) and phosphorylation of mTOR was observed by MG administration. However, autophagy inhibition with 3-methyladenine (3-MA) in HepG2 cells drastically abrogated the MG-mediated suppression of inflammation and lipid metabolism. In conclusion, MG inhibited hepatic steatosis-induced NLRP3 inflammasome activation through the restoration of autophagy to promote HO-1 signaling capable of ameliorating oxidative stress and inflammatory responses.
Collapse
|
|
30
|
Li S, Eguchi N, Lau H, Ichii H. The Role of the Nrf2 Signaling in Obesity and Insulin Resistance. Int J Mol Sci 2020; 21:ijms21186973. [PMID: 32971975 PMCID: PMC7555440 DOI: 10.3390/ijms21186973] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 09/03/2020] [Accepted: 09/17/2020] [Indexed: 12/15/2022] Open
Abstract
Obesity, a metabolic disorder characterized by excessive accumulation of adipose tissue, has globally become an increasingly prevalent disease. Extensive studies have been conducted to elucidate the underlying mechanism of the development of obesity. In particular, the close association of inflammation and oxidative stress with obesity has become increasingly evident. Obesity has been shown to exhibit augmented levels of circulating proinflammatory cytokines, which have been associated with the activation of pathways linked with inflammation-induced insulin resistance, a major pathological component of obesity and several other metabolic disorders. Oxidative stress, in addition to its role in stimulating adipose differentiation, which directly triggers obesity, is considered to feed into this pathway, further aggravating insulin resistance. Nuclear factor E2 related factor 2 (Nrf2) is a basic leucine zipper transcription factor that is activated in response to inflammation and oxidative stress, and responds by increasing antioxidant transcription levels. Therefore, Nrf2 has emerged as a critical new target for combating insulin resistance and subsequently, obesity. However, the effects of Nrf2 on insulin resistance and obesity are controversial. This review focuses on the current state of research on the interplay of inflammation and oxidative stress in obesity, the role of the Nrf2 pathway in obesity and insulin resistance, and the potential use of Nrf2 activators for the treatment of insulin resistance.
Collapse
Affiliation(s)
- Shiri Li
- Correspondence: (S.L.); (H.I.); Tel.: +1-(714)-456-5160 (S.L.); +1-(714)-456-8590 (H.I.)
| | | | | | - Hirohito Ichii
- Correspondence: (S.L.); (H.I.); Tel.: +1-(714)-456-5160 (S.L.); +1-(714)-456-8590 (H.I.)
| |
Collapse
|
|
31
|
Gambelunghe A, Giovagnoli S, Di Michele A, Boncompagni S, Dell’Omo M, Leopold K, Iavicoli I, Talesa VN, Antognelli C. Redox-Sensitive Glyoxalase 1 Up-Regulation Is Crucial for Protecting Human Lung Cells from Gold Nanoparticles Toxicity. Antioxidants (Basel) 2020; 9:E697. [PMID: 32756399 PMCID: PMC7463694 DOI: 10.3390/antiox9080697] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 07/24/2020] [Accepted: 07/27/2020] [Indexed: 12/19/2022] Open
Abstract
Gold nanoparticles (AuNPs) are considered nontoxic upon acute exposure, at least when they are equal or above 5 nm size. However, the safeguard mechanisms contributing to maintain cell viability are scarcely explored so far. Here, we investigated the cyto-protective role of Glyoxalase 1 (Glo1), a key enzyme involved in the control of deleterious dicarbonyl stress, in two human cell types of the respiratory tract, after an acute exposure to AuNPs with a main size of 5 nm. We found that the redox sensitive Nrf-2-mediated up-regulation of Glo1 was crucial to protect cells from AuNPs-induced toxicity. However, cells challenged with a pro-inflammatory/pro-oxidative insult become susceptible to the pro-apoptotic effect of AuNPs. Notably, the surviving cells undergo epigenetic changes associated with the onset of a partial epithelial to mesenchymal transition (EMT) process (metastable phenotype), driven by the increase in dicarbonyl stress, consequent to Glo1 inactivation. As a physiological respiratory epithelium is required for the normal respiratory function, the knowledge of the protective mechanisms avoiding or (when challenged) promoting its modification/damage might provide insight into the genesis, and, most importantly, prevention of potential health effects that might occur in subjects exposed to AuNPs, through targeted surveillance programs, at least under specific influencing factors.
Collapse
Affiliation(s)
- Angela Gambelunghe
- Department of Medicine, University of Perugia, 06123 Perugia, Italy; (A.G.); (M.D.)
| | - Stefano Giovagnoli
- Department of Pharmaceutical Sciences, University of Perugia, 06123 Perugia, Italy;
| | | | - Simona Boncompagni
- Department of Neuroscience, University G. d’ Annunzio of Chieti, Imaging and Clinical Sciences (DNICS) & Center for Advanced Studies and Technologies (CAST), 66100 Chieti, Italy;
| | - Marco Dell’Omo
- Department of Medicine, University of Perugia, 06123 Perugia, Italy; (A.G.); (M.D.)
| | - Kerstin Leopold
- Institute of Analytical and Bioanalytical Chemistry (IABC), Ulm University, 89081 Ulm, Germany;
| | - Ivo Iavicoli
- Department of Public Health, Section of Occupational Medicine, University of Naples Federico II, 80131 Naples, Italy;
| | | | - Cinzia Antognelli
- Department of Experimental Medicine, University of Perugia, 06123 Perugia, Italy;
| |
Collapse
|
|
32
|
Mani BK, Osborne-Lawrence S, Metzger N, Zigman JM. Lowering oxidative stress in ghrelin cells stimulates ghrelin secretion. Am J Physiol Endocrinol Metab 2020; 319:E330-E337. [PMID: 32543942 PMCID: PMC7473909 DOI: 10.1152/ajpendo.00119.2020] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Ghrelin is a predominantly stomach-derived peptide hormone with many actions including regulation of food intake, body weight, and blood glucose. Plasma ghrelin levels are robustly regulated by feeding status, with its levels increasing upon caloric restriction and decreasing after food intake. At least some of this regulation might be due to direct responsiveness of ghrelin cells to changes in circulating nutrients, including glucose. Indeed, oral and parental glucose administration to humans and mice lower plasma ghrelin. Also, dissociated mouse gastric mucosal cell preparations, which contain ghrelin cells, decrease ghrelin secretion when cultured in high ambient glucose. Here, we used primary cultures of mouse gastric mucosal cells in combination with an array of pharmacological tools to examine the potential role of changed intracellular oxidative stress in glucose-restricted ghrelin secretion. The antioxidants resveratrol, SRT1720, and curcumin all markedly increased ghrelin secretion. Furthermore, three different selective activators of Nuclear factor erythroid-derived-2-like 2 (Nrf2), a master regulator of the antioxidative cellular response to oxidative stress, increased ghrelin secretion. These antioxidant compounds blocked the inhibitory effects of glucose on ghrelin secretion. Therefore, we conclude that lowering oxidative stress within ghrelin cells stimulates ghrelin secretion and blocks the direct effects of glucose on ghrelin cells to inhibit ghrelin secretion.
Collapse
Affiliation(s)
- Bharath K Mani
- Center for Hypothalamic Research and Division of Endocrinology, Department of Internal Medicine and Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Sherri Osborne-Lawrence
- Center for Hypothalamic Research and Division of Endocrinology, Department of Internal Medicine and Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Nathan Metzger
- Center for Hypothalamic Research and Division of Endocrinology, Department of Internal Medicine and Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Jeffrey M Zigman
- Center for Hypothalamic Research and Division of Endocrinology, Department of Internal Medicine and Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas
| |
Collapse
|
|
33
|
Farkhondeh T, Folgado SL, Pourbagher-Shahri AM, Ashrafizadeh M, Samarghandian S. The therapeutic effect of resveratrol: Focusing on the Nrf2 signaling pathway. Biomed Pharmacother 2020; 127:110234. [PMID: 32559855 DOI: 10.1016/j.biopha.2020.110234] [Citation(s) in RCA: 148] [Impact Index Per Article: 29.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 04/20/2020] [Accepted: 05/03/2020] [Indexed: 12/18/2022] Open
Abstract
Resveratrol is a natural polyphenol derived from grapes, berries, red wine, peanuts amongst other fruits and nuts. Beneficial effects such as anti-inflammatory, antioxidant, hepatoprotective, neuroprotective, cardioprotective, renoprotective, anti-obesity, anti-diabetic, and anti-cancer of resveratrol have been demonstrated by preclinical and clinical research. A possibility is that these therapeutical effects are associated with modulation of the Nrf2 signaling pathway in the following way: resveratrol may potentiate Nrf2 signaling through blockage of Keap1, by means of changing the Nrf2 mediators, its expression and its nuclear translocation. This article reviews the evidence of the Nrf2 modulating hypothesis as a possible molecular mechanism underlying the medicinal properties of resveratrol.
Collapse
Affiliation(s)
- Tahereh Farkhondeh
- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Silvia Llorens Folgado
- Department of Medical Sciences, Faculty of Medicine of Albacete, Centro Regional de Investigaciones Biomédicas (CRIB), University of Castilla-La Mancha, 02008, Albacete, Spain
| | | | - Milad Ashrafizadeh
- Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
| | - Saeed Samarghandian
- Healthy Ageing Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran.
| |
Collapse
|
|
34
|
Cold-Pressed Nigella Sativa Oil Standardized to 3% Thymoquinone Potentiates Omega-3 Protection against Obesity-Induced Oxidative Stress, Inflammation, and Markers of Insulin Resistance Accompanied with Conversion of White to Beige Fat in Mice. Antioxidants (Basel) 2020; 9:antiox9060489. [PMID: 32512788 PMCID: PMC7346210 DOI: 10.3390/antiox9060489] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 05/27/2020] [Accepted: 06/01/2020] [Indexed: 12/11/2022] Open
Abstract
Excessive lipid accumulation in white adipose tissue (WAT) results in adipocyte hypertrophy and chronic low-grade inflammation, which is the major cause of obesity-associated insulin resistance and consequent metabolic disease. The development of beige adipocytes in WAT (browning of WAT) increases energy expenditure and has been considered as a novel strategy to counteract obesity. Thymoquinone (TQ) is the main bioactive quinone derived from the plant Nigella Sativa and has antioxidative and anti-inflammatory capacities. Fish oil omega 3 (ω3) enhances both insulin sensitivity and glucose homeostasis in obesity, but the involved mechanisms remain unclear. The aim of this study is to explore the effects of TQ and ω3 PUFAs (polyunsaturated fatty acids) on obesity-associated inflammation, markers of insulin resistance, and the metabolic effects of adipose tissue browning. 3T3-L1 cells were cultured to investigate the effects of TQ and ω3 on the browning of WAT. C57BL/6J mice were fed a high-fat diet (HFD), supplemented with 0.75% TQ, and 2% ω3 in combination for eight weeks. In 3T3-L1 cells, TQ and ω3 reduced lipid droplet size and increased hallmarks of beige adipocytes such as uncoupling protein-1 (UCP1), PR domain containing 16 (PRDM16), fibroblast growth factor 21 (FGF21), Sirtuin 1 (Sirt1), Mitofusion 2 (Mfn2), and heme oxygenase 1 (HO-1) protein expression, as well as increased the phosphorylation of Protein Kinase B (AKT) and insulin receptors. In the adipose tissue of HFD mice, TQ and ω3 treatment attenuated levels of inflammatory adipokines, Nephroblastoma Overexpressed (NOV/CCN3) and Twist related protein 2 (TWIST2), and diminished adipocyte hypoxia by decreasing HIF1α expression and hallmarks of beige adipocytes such as UCP1, PRDM16, FGF21, and mitochondrial biogenesis markers Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), Sirt1, and Mfn2. Increased 5′ adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation and HO-1 expression were observed in adipose with TQ and ω3 treatment, which led to increased pAKT and pIRS1 Ser307 expression. In addition to the adipose, TQ and ω3 also increased inflammation and markers of insulin sensitivity in the liver, as demonstrated by increased phosphorylated insulin receptor (pIR tyr972), insulin receptor beta (IRβ), UCP1, and pIRS1 Ser307 and reduced NOV/CCN3 expression. Our data demonstrate the enhanced browning of WAT from TQ treatment in combination with ω3, which may play an important role in decreasing obesity-associated insulin resistance and in reducing the chronic inflammatory state of obesity.
Collapse
|
|
35
|
Zhang H, Chen Y, Chen Y, Jia P, Ji S, Xu J, Li Y, Wang T. Comparison of the effects of resveratrol and its derivative pterostilbene on hepatic oxidative stress and mitochondrial dysfunction in piglets challenged with diquat. Food Funct 2020; 11:4202-4215. [PMID: 32352466 DOI: 10.1039/d0fo00732c] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
This study investigated the potential of resveratrol (RSV) and its derivative pterostilbene (PT) to prevent diquat (DQ)-induced hepatic oxidative damage and mitochondrial dysfunction in piglets. Seventy-two weanling piglets were randomly divided into the following treatment groups: non-challenged control group, DQ-challenged control group, and DQ-challenged groups supplemented with either 300 mg RSV per kg of diet or an equivalent amount of PT. Each treatment group consisted of six replicates with three piglets per replicate (n = 6). After a two-week feeding trial, piglets were intraperitoneally injected with either 10 mg DQ per kg of body weight or sterile saline. At 24 hours post-injection, one piglet from each replicate (six piglets per treatment) was randomly selected for sample collection and biochemical analysis. Compared with the DQ-challenged control group, PT attenuated the growth loss of piglets after the DQ challenge (P < 0.05). Administration of PT was more effective than its parent compound in inhibiting the DQ-induced hepatic apoptosis and the increased generation of total cholesterol, superoxide anion, and lipid peroxidation products (P < 0.05). Specifically, PT facilitated nuclear factor erythroid 2-related factor 2 signals and the expression and activity of manganese superoxide dismutase, while it also prevented mitochondrial swelling, membrane potential collapse, and adenosine triphosphate depletion, possibly through the activation of sirtuin 1 (P < 0.05). These results indicate that PT may be superior to RSV as an antioxidant to protect the liver of young piglets from oxidative insults.
Collapse
Affiliation(s)
- Hao Zhang
- College of Animal Science & Technology, Nanjing Agricultural University, Nanjing 210095, China.
| | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Zunkel K, Simm A, Bartling B. Long-term intake of the reactive metabolite methylglyoxal is not toxic in mice. Food Chem Toxicol 2020; 141:111333. [PMID: 32298726 DOI: 10.1016/j.fct.2020.111333] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 03/13/2020] [Accepted: 04/08/2020] [Indexed: 01/09/2023]
Abstract
Reactive carbonyls, including methylglyoxal (MG), are considered toxic compounds in foodstuffs because they irreversibly modify proteins and produce advanced glycation end products (AGEs). Therefore, we studied the long-term effect of increased MG intake in mature adult mice. Six-month-old C57BL/6N mice received MG by drinking water (2.5 mg/ml; i.e., 200-300 mg/kg BW/d) until death. This treatment caused an immediate strong increase in urine MG and a delayed moderate increase in plasma MG. At 24 months of age, mice administered MG showed no changes in the blood and tissue activity of glyoxalase-1 (Glo1), an intracellular MG-detoxifying enzyme; no signs of renal insufficiency and diabetes, including unchanged AGE modifications of plasma and vessel proteins; reduced tumour incidence; and slightly increased survival. Mice simultaneously deficient in the receptor for AGEs (RAGE) and overexpressing Glo1 exhibited higher basal plasma MG levels and did generally not respond to long-term MG intake. In vitro experiments supported the minor relevance of Glo1 in the detoxification of circulating MG but the important role of plasma albumin as an MG scavenger. In conclusion, the detoxification of dietary MG through renal excretion and further mechanisms largely prevents the toxicity of MG and possibly other food-derived reactive carbonyls in mature adults.
Collapse
Affiliation(s)
- Katja Zunkel
- Department of Cardiac Surgery, Mid-German Heart Centre, University Hospital Halle (Saale), Martin Luther University Halle-Wittenberg, Halle (Saale), Germany
| | - Andreas Simm
- Department of Cardiac Surgery, Mid-German Heart Centre, University Hospital Halle (Saale), Martin Luther University Halle-Wittenberg, Halle (Saale), Germany
| | - Babett Bartling
- Department of Cardiac Surgery, Mid-German Heart Centre, University Hospital Halle (Saale), Martin Luther University Halle-Wittenberg, Halle (Saale), Germany; Department of Animal Health Management, Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
| |
Collapse
|
|
37
|
Abstract
Polyphenols are naturally occurring compounds in plants and they are the most abundant antioxidants in the human diet. Due to their considerable structural diversity, this largely influences their bioavailability. Since a large proportion of polyphenols remains unabsorbed along the gastrointestinal tract, they may accumulate in the large intestine, where most of them are extensively metabolized by the intestinal microbiota. The formation of bioactive polyphenol-derived metabolites may also benefit the health status of the subjects, although the mechanisms have not been delineated. This review aims to highlight the impact of polyphenols on gut health and the modes of action could be through modulation of intestinal barrier function, innate and adaptive immune response, signaling pathways, as well as the ability to modify gut microbiota composition. The review will conclude by presenting future perspective and challenges of polyphenols application in food products to be used for preventing or treating diseases.
Collapse
Affiliation(s)
- Murphy L Y Wan
- School of Biological Sciences, Faculty of Science, Kadoorie Biological Sciences Building, The University of Hong Kong, Pokfulam, Hong Kong
| | - Vanessa Anna Co
- School of Biological Sciences, Faculty of Science, Kadoorie Biological Sciences Building, The University of Hong Kong, Pokfulam, Hong Kong
| | - Hani El-Nezami
- School of Biological Sciences, Faculty of Science, Kadoorie Biological Sciences Building, The University of Hong Kong, Pokfulam, Hong Kong.,Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| |
Collapse
|
|
38
|
Patel DM, Bose M, Cooper ME. Glucose and Blood Pressure-Dependent Pathways-The Progression of Diabetic Kidney Disease. Int J Mol Sci 2020; 21:ijms21062218. [PMID: 32210089 PMCID: PMC7139394 DOI: 10.3390/ijms21062218] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 03/17/2020] [Accepted: 03/17/2020] [Indexed: 12/11/2022] Open
Abstract
The major clinical associations with the progression of diabetic kidney disease (DKD) are glycemic control and systemic hypertension. Recent studies have continued to emphasize vasoactive hormone pathways including aldosterone and endothelin which suggest a key role for vasoconstrictor pathways in promoting renal damage in diabetes. The role of glucose per se remains difficult to define in DKD but appears to involve key intermediates including reactive oxygen species (ROS) and dicarbonyls such as methylglyoxal which activate intracellular pathways to promote fibrosis and inflammation in the kidney. Recent studies have identified a novel molecular interaction between hemodynamic and metabolic pathways which could lead to new treatments for DKD. This should lead to a further improvement in the outlook of DKD building on positive results from RAAS blockade and more recently newer classes of glucose-lowering agents such as SGLT2 inhibitors and GLP1 receptor agonists.
Collapse
Affiliation(s)
- Devang M. Patel
- Department of Diabetes, Monash University Central, Clinical School, Melbourne, VIC 3004, Australia;
- Correspondence: (D.M.P.); (M.E.C.)
| | - Madhura Bose
- Department of Diabetes, Monash University Central, Clinical School, Melbourne, VIC 3004, Australia;
| | - Mark E. Cooper
- Department of Diabetes, Monash University Central, Clinical School, Melbourne, VIC 3004, Australia;
- Department of Endocrinology and Diabetes, The Alfred Hospital, Melbourne, VIC 3004, Australia
- Correspondence: (D.M.P.); (M.E.C.)
| |
Collapse
|
|
39
|
Wang J, Wu T, Fang L, Liu C, Liu X, Li H, Shi J, Li M, Min W. Peptides from walnut (Juglans mandshurica Maxim.) protect hepatic HepG2 cells from high glucose-induced insulin resistance and oxidative stress. Food Funct 2020; 11:8112-8121. [DOI: 10.1039/d0fo01753a] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Schematic of the mechanism underlying the protection of hepatic HepG2 cells against high glucose-induced insulin resistance and oxidative stress by walnut-derived peptides.
Collapse
Affiliation(s)
- Ji Wang
- College of Food Science and Engineering
- Jilin Agricultural University
- Changchun
- P. R. China
- National Engineering Laboratory of Wheat and Corn Deep Processing
| | - Tong Wu
- College of Food Science and Engineering
- Jilin Agricultural University
- Changchun
- P. R. China
- National Engineering Laboratory of Wheat and Corn Deep Processing
| | - Li Fang
- College of Food Science and Engineering
- Jilin Agricultural University
- Changchun
- P. R. China
- National Engineering Laboratory of Wheat and Corn Deep Processing
| | - Chunlei Liu
- College of Food Science and Engineering
- Jilin Agricultural University
- Changchun
- P. R. China
- National Engineering Laboratory of Wheat and Corn Deep Processing
| | - Xiaoting Liu
- College of Food Science and Engineering
- Jilin Agricultural University
- Changchun
- P. R. China
- National Engineering Laboratory of Wheat and Corn Deep Processing
| | - Hongmei Li
- College of Food Science and Engineering
- Jilin Agricultural University
- Changchun
- P. R. China
- National Engineering Laboratory of Wheat and Corn Deep Processing
| | - Junhua Shi
- College of Food Science and Engineering
- Jilin Agricultural University
- Changchun
- P. R. China
- National Engineering Laboratory of Wheat and Corn Deep Processing
| | - Meihe Li
- College of Food Science and Engineering
- Jilin Agricultural University
- Changchun
- P. R. China
- National Engineering Laboratory of Wheat and Corn Deep Processing
| | - Weihong Min
- College of Food Science and Engineering
- Jilin Agricultural University
- Changchun
- P. R. China
- National Engineering Laboratory of Wheat and Corn Deep Processing
| |
Collapse
|
|
40
|
Schalkwijk CG, Stehouwer CDA. Methylglyoxal, a Highly Reactive Dicarbonyl Compound, in Diabetes, Its Vascular Complications, and Other Age-Related Diseases. Physiol Rev 2020; 100:407-461. [DOI: 10.1152/physrev.00001.2019] [Citation(s) in RCA: 368] [Impact Index Per Article: 73.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The formation and accumulation of methylglyoxal (MGO), a highly reactive dicarbonyl compound, has been implicated in the pathogenesis of type 2 diabetes, vascular complications of diabetes, and several other age-related chronic inflammatory diseases such as cardiovascular disease, cancer, and disorders of the central nervous system. MGO is mainly formed as a byproduct of glycolysis and, under physiological circumstances, detoxified by the glyoxalase system. MGO is the major precursor of nonenzymatic glycation of proteins and DNA, subsequently leading to the formation of advanced glycation end products (AGEs). MGO and MGO-derived AGEs can impact on organs and tissues affecting their functions and structure. In this review we summarize the formation of MGO, the detoxification of MGO by the glyoxalase system, and the biochemical pathways through which MGO is linked to the development of diabetes, vascular complications of diabetes, and other age-related diseases. Although interventions to treat MGO-associated complications are not yet available in the clinical setting, several strategies to lower MGO have been developed over the years. We will summarize several new directions to target MGO stress including glyoxalase inducers and MGO scavengers. Targeting MGO burden may provide new therapeutic applications to mitigate diseases in which MGO plays a crucial role.
Collapse
Affiliation(s)
- C. G. Schalkwijk
- CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands; and Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - C. D. A. Stehouwer
- CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands; and Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands
| |
Collapse
|
|
41
|
Psoralea corylifolia L. Seed Extract Attenuates Methylglyoxal-Induced Insulin Resistance by Inhibition of Advanced Glycation End Product Formation. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:4310319. [PMID: 31976027 PMCID: PMC6954480 DOI: 10.1155/2019/4310319] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/13/2019] [Revised: 10/31/2019] [Accepted: 12/05/2019] [Indexed: 01/11/2023]
Abstract
Accumulation of advanced glycation end products (AGEs) in the body has been implicated in the pathogenesis of metabolic conditions, such as diabetes mellitus. Methylglyoxal (MGO), a major precursor of AGEs, has been reported to induce insulin resistance in both in vitro and in vivo studies. Psoralea corylifolia seeds (PCS) have been used as a traditional medicine for several diseases, but their potential application in treating insulin resistance has not yet been evaluated. This study is aimed at investigating whether PCS extract could attenuate insulin resistance induced by MGO. Male C57BL/6N mice (6 weeks old) were administered 1% MGO in their drinking water for 18 weeks, and the PCS extract (200 or 500 mg/kg) was orally administered daily from the first day of the MGO administration. We observed that both 200 and 500 mg/kg PCS extract treatment significantly improved glucose tolerance and insulin sensitivity and markedly restored p-Akt and p-IRS1/2 expression in the livers of the MGO-administered mice. Additionally, the PCS extract significantly increased the phosphorylation of Akt and IRS-1/2 and glucose uptake in MGO-treated HepG2 cells. Further studies showed that the PCS extract inhibited MGO-induced AGE formation in the HepG2 cells and in the sera of MGO-administered mice. PCS extract also increased the expression of glyoxalase 1 (GLO1) in the liver tissue of MGO-administered mice. The PCS extract significantly decreased the phosphorylation of ERK, p38, and NF-κB and suppressed the mRNA expression of proinflammatory molecules including TNF-α and IL-1β and iNOS in MGO-administered mice. Additionally, we demonstrated that the PCS extract attenuated oxidative stress, as evidenced by the reduced ROS production in the MGO-treated cells and the enhanced expression of antioxidant enzymes in the liver of MGO-administered mice. Thus, PCS extract ameliorated the MGO-induced insulin resistance in HepG2 cells and in mice by reducing oxidative stress via the inhibition of AGE formation. These findings suggest the potential of PCS extract as a candidate for the prevention and treatment of insulin resistance.
Collapse
|
|
42
|
Taïbi N, Taïbi A, Ameraoui R, Abou-Mustapha M, Hadjadj M, Boutaiba ZM, Kaced A, Djema S, Al-Balas QA, Al Jabal GA, Aissi M, Harhoura K, Zenia S, Khammar F. Development of analytical methods GC-MS vs LC-UV for the serum monitoring of an inflammatory glycotoxin (methylglyoxal): A new biomarker of bovine hepatobiliary distomatosis. Biochimie 2019; 168:169-184. [PMID: 31707099 DOI: 10.1016/j.biochi.2019.11.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2019] [Accepted: 11/03/2019] [Indexed: 01/22/2023]
Abstract
Two analytical methods; high performance liquid chromatography and gas chromatography were used to determine the content of 2-methylquinoxaline, a methylglyoxal-derived agent in sera from cattle with fascioliasis. Methylglyoxal is a highly mutagenic and cytotoxic reactive dicarbonyl compound formed by non-enzymatic fragmentation of triose phosphate GAP and DHAP during glycolysis which regularly contributes to repositioning the energetic balance between physiological and pathological situations. The aim of this study was to propose the MGO as a new biomarker in the bovine fasciolosis. Strongly infected animals showed a correlation between the relatively high levels of Fasciola hepatica anti-f2 antibody and methylglyoxal compared to unharmed animals. Also, an acute hyperglycemia was recorded and closely related to hepatic parenchyma hyperplasia, inflammation, bile ducts obstruction and scléro-fibrous foci formation.Unlike HPLC, which has shown analytical flaws and irregularities, GC-MS remains an excellent diagnostic tool for detecting and quantifying methylglyoxal in biological fluids. The developed method has been validated under FDA guidelines. A full scan-range was set from m/z 39 to 144/999 and the molecular weight of the 2-methylquinoxaline was identified according to NIST Database and ES. Methylglyoxal was the only analyte successfully quantified in a relatively short run time. It was linear over a concentration range of 0.057-5.7 μg.ml-1with mean recoveries and RSD of 118% and 3.63% respectively. The intra and inter-day assays were satisfying and not exceed 3.00%. Results reflect the degree of precision of our method and indicate that MGO was an important contributor to understand the hepatic failure independently of other serum markers.
Collapse
Affiliation(s)
- Nadia Taïbi
- Centre de Recherche Scientifique et Technique en Analyses Physico-chimiques CRAPC, BP 384, Bou-Ismail, 42004, Tipaza, Algeria; Université des Sciences et de La Technologie Houari Boumediene (USTHB), Faculté des Sciences Biologiques (FSB), Laboratoire de Recherche sur Les Zones Arides, (LRZA), BP 32 El Alia 16111, Bab Ezzouar, 16111, Algeria.
| | - Amina Taïbi
- Laboratoire de Parasitologie et Mycologie, Laboratoire de Recherche Santé et Production Animale, École Nationale Supérieure Vétérinaire, B.P. 228, Rue Issad Abbes, El Alia, Oued Smar, Alger, Algeria.
| | - Rachid Ameraoui
- Centre de Recherche Scientifique et Technique en Analyses Physico-chimiques CRAPC, BP 384, Bou-Ismail, 42004, Tipaza, Algeria.
| | - Mohamed Abou-Mustapha
- Centre de Recherche Scientifique et Technique en Analyses Physico-chimiques CRAPC, BP 384, Bou-Ismail, 42004, Tipaza, Algeria.
| | - Mohamed Hadjadj
- Centre de Recherche Scientifique et Technique en Analyses Physico-chimiques CRAPC, BP 384, Bou-Ismail, 42004, Tipaza, Algeria.
| | - Zahra-Mouna Boutaiba
- Centre de Recherche Scientifique et Technique en Analyses Physico-chimiques CRAPC, BP 384, Bou-Ismail, 42004, Tipaza, Algeria.
| | - Amel Kaced
- Centre de Recherche Scientifique et Technique en Analyses Physico-chimiques CRAPC, BP 384, Bou-Ismail, 42004, Tipaza, Algeria.
| | - Souhila Djema
- Centre de Recherche Scientifique et Technique en Analyses Physico-chimiques CRAPC, BP 384, Bou-Ismail, 42004, Tipaza, Algeria.
| | - Qosay-Ali Al-Balas
- Department of Medicinal Chemistry and Pharmacognosy Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
| | - Ghazi-Ahmad Al Jabal
- Department of Medicinal Chemistry and Pharmacognosy Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
| | - Miriem Aissi
- Laboratoire de Parasitologie et Mycologie, Laboratoire de Recherche Santé et Production Animale, École Nationale Supérieure Vétérinaire, B.P. 228, Rue Issad Abbes, El Alia, Oued Smar, Alger, Algeria.
| | - Khaled Harhoura
- Laboratoire de Parasitologie et Mycologie, Laboratoire de Recherche Santé et Production Animale, École Nationale Supérieure Vétérinaire, B.P. 228, Rue Issad Abbes, El Alia, Oued Smar, Alger, Algeria.
| | - Safia Zenia
- Laboratoire de Parasitologie et Mycologie, Laboratoire de Recherche Santé et Production Animale, École Nationale Supérieure Vétérinaire, B.P. 228, Rue Issad Abbes, El Alia, Oued Smar, Alger, Algeria.
| | - Farida Khammar
- Université des Sciences et de La Technologie Houari Boumediene (USTHB), Faculté des Sciences Biologiques (FSB), Laboratoire de Recherche sur Les Zones Arides, (LRZA), BP 32 El Alia 16111, Bab Ezzouar, 16111, Algeria.
| |
Collapse
|
|
43
|
Yang J, Zhang F, Shi H, Gao Y, Dong Z, Ma L, Sun X, Li X, Chang S, Wang Z, Qu Y, Li H, Hu K, Sun A, Ge J. Neutrophil-derived advanced glycation end products-Nε-(carboxymethyl) lysine promotes RIP3-mediated myocardial necroptosis via RAGE and exacerbates myocardial ischemia/reperfusion injury. FASEB J 2019; 33:14410-14422. [PMID: 31665609 DOI: 10.1096/fj.201900115rr] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Nε-(carboxymethyl) lysine (CML), the major member of advanced glycation end products, was widely studied in diabetic complications and aging-associated diseases. However, the impact of CML on myocardial ischemia/reperfusion injury (MI/RI) was rarely reported. In the present study, CML was increased in both patients with acute myocardial infarction (53.4 ± 7.8 vs. 28.1 ± 4.4 ng; P = 0.017), and mice underwent MI/RI (16.4 ± 1.4 vs. 10.8 ± 0.9 ng; P = 0.006). Depletion of neutrophils reduced CML (17.8 ± 1.0 vs. 9.9 ± 0.3 ng; P < 0.001), indicating neutrophils were the major cells contributing to CML formation during MI/RI. CML treatment exacerbated MI/RI by elevating myocardial injury marker (274.3 ± 18.0 vs. 477.2 ± 34.3 pg; P < 0.001), enlarging myocardial infarct size (32.9 ± 3.6 vs. 45.2 ± 3.8%; P = 0.03), increasing myocardial fibrosis (17.5 ± 1.6 vs. 29.7 ± 2.2%; P < 0.001) and impairing cardiac function (59.4 ± 2.4% vs. 46.0 ± 1.3%; P = 0.001). Further study revealed that CML increased the phosphorylation of receptor interacting protein (RIP) 3, an important initiator of necroptosis, and its downstream proteins. Receptor for advanced glycation end product (RAGE) deficiency effectively blocked RIP3 phosphorylation induced by CML and rescued CML-mediated MI/RI, indicating CML promoted RIP3-mediated necroptosis through RAGE. In addition, glyoxalase-1 overexpression could effectively attenuate MI/RI by reducing CML formation, providing a potential therapeutic target for MI/RI.-Yang, J., Zhang, F., Shi, H., Gao, Y., Dong, Z., Ma, L., Sun, X., Li, X., Chang, S., Wang, Z., Qu, Y., Li, H., Hu, K., Sun, A., Ge, J. Neutrophil-derived advanced glycation end products-Nε-(carboxymethyl) lysine promotes RIP3-mediated myocardial necroptosis via RAGE and exacerbates myocardial ischemia/reperfusion injury.
Collapse
Affiliation(s)
- Ji'e Yang
- Department of Cardiology, Zhongshan Hospital, Institute of Cardiovascular Diseases, Fudan University, Shanghai, China
| | - Feng Zhang
- Department of Cardiology, Zhongshan Hospital, Institute of Cardiovascular Diseases, Fudan University, Shanghai, China
| | - Huairui Shi
- Department of Cardiology, Zhongshan Hospital, Institute of Cardiovascular Diseases, Fudan University, Shanghai, China
| | - Yang Gao
- Department of Cardiology, Zhongshan Hospital, Institute of Cardiovascular Diseases, Fudan University, Shanghai, China
| | - Zhen Dong
- Department of Cardiology, Zhongshan Hospital, Institute of Cardiovascular Diseases, Fudan University, Shanghai, China
| | - Leilei Ma
- Department of Cardiology, Zhongshan Hospital, Institute of Cardiovascular Diseases, Fudan University, Shanghai, China
| | - Xiaolei Sun
- Institute of Biomedical Science, Fudan University, Shanghai, China
| | - Xiao Li
- Institute of Biomedical Science, Fudan University, Shanghai, China
| | - Suchi Chang
- Department of Cardiology, Zhongshan Hospital, Institute of Cardiovascular Diseases, Fudan University, Shanghai, China
| | - Zeng Wang
- Institute of Biomedical Science, Fudan University, Shanghai, China
| | - Yanan Qu
- Department of Cardiology, Zhongshan Hospital, Institute of Cardiovascular Diseases, Fudan University, Shanghai, China
| | - Hua Li
- Institute of Biomedical Science, Fudan University, Shanghai, China
| | - Kai Hu
- Department of Cardiology, Zhongshan Hospital, Institute of Cardiovascular Diseases, Fudan University, Shanghai, China
| | - Aijun Sun
- Department of Cardiology, Zhongshan Hospital, Institute of Cardiovascular Diseases, Fudan University, Shanghai, China.,Institute of Biomedical Science, Fudan University, Shanghai, China
| | - Junbo Ge
- Department of Cardiology, Zhongshan Hospital, Institute of Cardiovascular Diseases, Fudan University, Shanghai, China.,Institute of Biomedical Science, Fudan University, Shanghai, China
| |
Collapse
|
|
44
|
Hajizadeh-Sharafabad F, Sahebkar A, Zabetian-Targhi F, Maleki V. The impact of resveratrol on toxicity and related complications of advanced glycation end products: A systematic review. Biofactors 2019; 45:651-665. [PMID: 31185146 DOI: 10.1002/biof.1531] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2019] [Accepted: 05/17/2019] [Indexed: 12/12/2022]
Abstract
Accumulation of advanced glycation end products (AGEs) promotes the generation of free radicals, which leads to chronic oxidative stress predisposing to chronic oxidative stress, inflammation, and related diseases. This systematic review aimed to determine the effect of resveratrol (RSV) on AGE-induced toxicity and its deleterious consequences. A comprehensive search was performed through literature were published until December 2018 using relevant keywords. The databases that were used for the search were PubMed, Scopus, Embase, ProQuest, and Google Scholar. A total of 29 eligible studies were found and included in the review for the analysis. Except one, all studies showed suppressing effects for RSV on the production of AGEs or receptor for advanced glycation end products (RAGE) and its detrimental consequences including oxidative stress, inflammatory response, cellular immune reactions, insulin response, and atherosclerosis. RSV exerts its effects through influencing RAGE, nuclear factor kappa B (NF-κB), peroxisome proliferator-activated receptor (PPAR) γ, and transforming growth factor (TGF)-β activities. This review suggests that RSV has got potential to decrease AGEs toxicity and inhibit the AGE-induced complications. More clinical trials are suggested to evaluate the beneficial effect of RSV on AGEs in chronic metabolic diseases.
Collapse
MESH Headings
- Animals
- Antigens, Neoplasm/genetics
- Antigens, Neoplasm/metabolism
- Antioxidants/pharmacology
- Atherosclerosis/drug therapy
- Atherosclerosis/genetics
- Atherosclerosis/metabolism
- Atherosclerosis/pathology
- Diabetes Mellitus, Experimental/drug therapy
- Diabetes Mellitus, Experimental/genetics
- Diabetes Mellitus, Experimental/metabolism
- Diabetes Mellitus, Experimental/pathology
- Gene Expression Regulation
- Glycation End Products, Advanced/antagonists & inhibitors
- Glycation End Products, Advanced/genetics
- Glycation End Products, Advanced/metabolism
- Glycation End Products, Advanced/toxicity
- Humans
- Inflammation
- Mitogen-Activated Protein Kinases/genetics
- Mitogen-Activated Protein Kinases/metabolism
- NF-kappa B/genetics
- NF-kappa B/metabolism
- Oxidative Stress
- PPAR gamma/genetics
- PPAR gamma/metabolism
- Pyruvaldehyde/metabolism
- Resveratrol/pharmacology
- Signal Transduction
- Transforming Growth Factor beta1/genetics
- Transforming Growth Factor beta1/metabolism
Collapse
Affiliation(s)
- Fatemeh Hajizadeh-Sharafabad
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Nutrition, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amirhossein Sahebkar
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fateme Zabetian-Targhi
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
| | - Vahid Maleki
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Nutrition, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
- Nutrition Research Center, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| |
Collapse
|
|
45
|
Wang Z, Zhao D, Chen L, Li J, Yuan G, Yang G, Zhang H, Guo X, Zhang J. Glycine increases glyoxalase-1 function by promoting nuclear factor erythroid 2-related factor 2 translocation into the nucleus of kidney cells of streptozotocin-induced diabetic rats. J Diabetes Investig 2019; 10:1189-1198. [PMID: 30825261 PMCID: PMC6717822 DOI: 10.1111/jdi.13032] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Revised: 02/12/2019] [Accepted: 02/27/2019] [Indexed: 12/28/2022] Open
Abstract
AIMS/INTRODUCTION We have previously reported that glycine suppresses the advanced glycation end-products signaling pathway and mitigates subsequent oxidative stress in the kidneys of diabetic rats. In the present study, we investigated whether this beneficial effect was associated with upregulation of glyoxalase-1 (Glo1) and activation of the nuclear factor erythroid 2-related factor 2 (Nrf2). MATERIALS AND METHODS Both healthy rats and streptozotocin-induced diabetic rats were administrated with glycine (1% added to the drinking water) for 12 weeks. The function of Glo1, messenger ribonucleic acid (mRNA) and protein expressions of Nrf2, and markers of oxidative status were measured in the kidneys. The mRNA expressions of other downstream signaling molecules of the Nrf2 pathway were also determined. RESULTS The mRNA and protein expressions, as well as the activity of Glo1, were decreased in the kidneys of diabetic rats, accompanied by diminished glutathione levels. After glycine treatment, these parameters of Glo1 function were markedly increased. Compared with the control group, the levels of Nrf2 mRNA and protein in the total kidney lysis were both markedly elevated in the diabetic group and glycine-treated group. However, the nuclear translocation of Nrf2 was significantly increased in the glycine-treated group than in the diabetic group. In addition, the anti-oxidant capacity and the expressions of other downstream molecules of the Nrf2 signaling pathway were significantly increased after glycine treatment. CONCLUSIONS The present study shows that glycine might enhance the function of Glo1 and restore anti-oxidant defense by promoting the nuclear translocation of Nrf2, thus inhibiting advanced glycation end-products formation and protecting against renal oxidative stress.
Collapse
Affiliation(s)
- Ziwei Wang
- EndocrinologyPeking University First HospitalBeijingChina
| | - Dan Zhao
- EndocrinologyPeking University First HospitalBeijingChina
| | - Lei Chen
- EndocrinologyPeking University First HospitalBeijingChina
| | - Jingjing Li
- EndocrinologyPeking University First HospitalBeijingChina
| | - Geheng Yuan
- EndocrinologyPeking University First HospitalBeijingChina
| | - Guosheng Yang
- Animal CenterPeking University First HospitalBeijingChina
| | - Hong Zhang
- EndocrinologyPeking University First HospitalBeijingChina
| | - Xiaohui Guo
- EndocrinologyPeking University First HospitalBeijingChina
| | - Junqing Zhang
- EndocrinologyPeking University First HospitalBeijingChina
| |
Collapse
|
|
46
|
Tan X, Li L, Wang J, Zhao B, Pan J, Wang L, Liu X, Liu X, Liu Z. Resveratrol Prevents Acrylamide-Induced Mitochondrial Dysfunction and Inflammatory Responses via Targeting Circadian Regulator Bmal1 and Cry1 in Hepatocytes. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:8510-8519. [PMID: 31294559 DOI: 10.1021/acs.jafc.9b03368] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Acrylamide, mainly formed in Maillard browning reaction during food processing, causes defects in liver circadian clock and mitochondrial function by inducing oxidative stress. Resveratrol is a polyphenol that has powerful antioxidant and anti-inflammatory activity. However, the preventive effects of resveratrol on acrylamide-triggered oxidative damage and circadian rhythm disorders are unclear at the current stage. The present research revealed that resveratrol pretreatment prevented acrylamide-induced cell death, mitochondrial dysfunction, and inflammatory responses in HepG2 liver cells. Acrylamide significantly triggered disorders of circadian genes transcription and protein expressions including Bmal1 and Cry 1 in primary hepatocytes, which were prevented by resveratrol pretreatment. Moreover, we found that the beneficial effects of resveratrol on stimulating Nrf2/NQO-1 pathway and mitochondrial respiration complex expressions in acrylamide-treated cells were Bmal1-dependent. Similarly, the inhibitory effects of resveratrol on inflammation signaling NF-κB were Cry1-dependent. In conclusion, these results demonstrated resveratrol could be a promising compound in suppressing acrylamide-induced hepatotoxicity and balancing the circadian clock.
Collapse
Affiliation(s)
- Xintong Tan
- Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering , Northwest A&F University , Yangling 712100 , China
| | - Ling Li
- Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering , Northwest A&F University , Yangling 712100 , China
| | - Jia Wang
- Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering , Northwest A&F University , Yangling 712100 , China
| | - Beita Zhao
- Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering , Northwest A&F University , Yangling 712100 , China
| | - Junru Pan
- Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering , Northwest A&F University , Yangling 712100 , China
| | - Leran Wang
- Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering , Northwest A&F University , Yangling 712100 , China
| | - Xiao Liu
- Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering , Northwest A&F University , Yangling 712100 , China
| | - Xuebo Liu
- Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering , Northwest A&F University , Yangling 712100 , China
| | - Zhigang Liu
- Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering , Northwest A&F University , Yangling 712100 , China
| |
Collapse
|
|
47
|
Bai F, Zhang B, Hou Y, Yao J, Xu Q, Xu J, Fang J. Xanthohumol Analogues as Potent Nrf2 Activators against Oxidative Stress Mediated Damages of PC12 Cells. ACS Chem Neurosci 2019; 10:2956-2966. [PMID: 31116948 DOI: 10.1021/acschemneuro.9b00171] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
The nuclear factor erythroid 2-related factor 2 (Nrf2), a master transcription factor controlling a series of cytoprotective genes, is closely associated with scavenging the reactive oxygen species and maintaining the intracellular redox balance. Accumulating evidence has indicated that activation of Nrf2 is efficient to block or retard oxidative stress mediated neurodegenerative disorders. Small molecules that contribute directly or indirectly to the Nrf2 activation thus are promising therapeutic agents. Herein, we screened xanthohumol and its analogues, and two analogues (11 and 12) were disclosed to possess low cytotoxicity and rescue PC12 cells from the hydrogen peroxide or 6-hydroxydopamine induced injuries. Molecular mechanism studies demonstrated that compounds 11 and 12 are potent Nrf2 activators by promoting the nuclear accumulation of Nrf2 and enhancing the cellular antioxidant defense system. More importantly, genetically silencing the Nrf2 expression shuts down the observed cytoprotection conferred by both compounds, supporting the critical involvement of Nrf2 for the cellular actions of compounds 11 and 12.
Collapse
Affiliation(s)
- Feifei Bai
- State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, 222 South Tianshui Road, Lanzhou 730000, China
| | - Baoxin Zhang
- State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, 222 South Tianshui Road, Lanzhou 730000, China
| | - Yanan Hou
- State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, 222 South Tianshui Road, Lanzhou 730000, China
| | - Juan Yao
- State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, 222 South Tianshui Road, Lanzhou 730000, China
| | - Qianhe Xu
- State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, 222 South Tianshui Road, Lanzhou 730000, China
| | - Jianqiang Xu
- School of Life Science and Medicine & Panjin Industrial Technology Institute, Dalian University of Technology, Panjin Campus, Panjin 124221, China
| | - Jianguo Fang
- State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, 222 South Tianshui Road, Lanzhou 730000, China
| |
Collapse
|
|
48
|
Glycine Suppresses AGE/RAGE Signaling Pathway and Subsequent Oxidative Stress by Restoring Glo1 Function in the Aorta of Diabetic Rats and in HUVECs. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:4628962. [PMID: 30944692 PMCID: PMC6421782 DOI: 10.1155/2019/4628962] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Accepted: 01/13/2019] [Indexed: 12/20/2022]
Abstract
Oxidative stress plays a crucial role in the pathogenesis of diabetic vascular complications. It is known that the accumulation of advanced glycation end products (AGEs) and the activation of the receptor of AGEs (RAGE) induce sustained oxidative stress in the vascular tissue. Growing evidence indicates that glycine, the simplest amino acid, exerts antioxidant and antiglycation effects and also improves vascular function. However, the mechanism whereby glycine protects vascular tissue against oxidative stress in models with diabetes has not been investigated. In the present study, we evaluated whether glycine can attenuate oxidative stress by suppressing the AGE/RAGE signaling pathway in the aorta of streptozotocin-induced diabetic rats and in human umbilical vascular endothelial cells (HUVECs). Our results showed that oral glycine administration increased NO content and ameliorated oxidative stress in the serum and aorta of diabetic rats. The AGE/RAGE signaling pathway in the aorta of diabetic rats was significantly attenuated by glycine treatment as manifested by decreases in levels of AGEs, RAGE, Nox4, and NF-κB p65. The suppressive effect of glycine on the formation of AGEs was associated with increased activity and expression of aortic glyoxalase-1 (Glo1), a crucial enzyme that degrades methylglyoxal (MG), the major precursor of AGEs. In MG-treated HUVECs, glycine restored the function of Glo1, suppressed the AGE/RAGE signaling pathway, and inhibited the generation of reactive oxygen species. In addition, the reduction in the formation of AGEs in HUVECs caused by glycine treatment was inhibited by Glo1 inhibition. Taken together, our study provides evidence that glycine might inhibit the AGE/RAGE pathway and subsequent oxidative stress by improving Glo1 function, thus protecting against diabetic macrovascular complications.
Collapse
|
|
49
|
Zhou MX, Li GH, Wu XY, Sun L, Li YR, Yang WJ, Ren DM, Wang XN, Xiang L, Lou HX, Shen T. (2S)-5,6,7,3′,4′-pentamethoxyflavanone, a citrus polymethoxyflavone ameliorates arsenic- and cigarette smoke extract-induced cytotoxicity via activating Nrf2-mediated defense system. J Funct Foods 2019. [DOI: 10.1016/j.jff.2019.01.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
|
|
50
|
Abstract
Significance: Obesity and type 2 diabetes mellitus are increasing globally. There is also increasing associated complications, such as non-alcoholic fatty liver disease (NAFLD) and vascular complications of diabetes. There is currently no licensed treatment for NAFLD and no recent treatments for diabetic complications. New approaches are required, particularly those addressing mechanism-based risk factors for health decline and disease progression. Recent Advances: Dicarbonyl stress is the abnormal accumulation of reactive dicarbonyl metabolites such as methylglyoxal (MG) leading to cell and tissue dysfunction. It is a potential driver of obesity, diabetes, and related complications that are unaddressed by current treatments. Increased formation of MG is linked to increased glyceroneogenesis and hyperglycemia in obesity and diabetes and also down-regulation of glyoxalase 1 (Glo1)-which provides the main enzymatic detoxification of MG. Glo1 functional genomics studies suggest that increasing Glo1 expression and activity alleviates dicarbonyl stress; slows development of obesity, related insulin resistance; and prevents development of diabetic nephropathy and other microvascular complications of diabetes. A new therapeutic approach constitutes small-molecule inducers of Glo1 expression-Glo1 inducers-exploiting a regulatory antioxidant response element in the GLO1 gene. A prototype Glo1 inducer, trans-resveratrol (tRES)-hesperetin (HESP) combination, in corrected insulin resistance, improved glycemic control and vascular inflammation in healthy overweight and obese subjects in clinical trial. Critical Issues: tRES and HESP synergize pharmacologically, and HESP likely overcomes the low bioavailability of tRES by inhibition of intestinal glucuronosyltransferases. Future Directions: Glo1 inducers may now be evaluated in Phase 2 clinical trials for treatment of NAFLD and vascular complications of diabetes.
Collapse
Affiliation(s)
- Naila Rabbani
- 1 Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, University Hospital , Coventry, United Kingdom .,2 Warwick Systems Biology Centre, Senate House, University of Warwick , Coventry, United Kingdom
| | - Paul J Thornalley
- 1 Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, University Hospital , Coventry, United Kingdom .,2 Warwick Systems Biology Centre, Senate House, University of Warwick , Coventry, United Kingdom
| |
Collapse
|