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1
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Zhang R, Kanki K. Glycolytic inhibition by resveratrol facilitates chondrocyte survival under glucose-deprived conditions and improves the viability of 3D-cultured cartilage tissue. J Biosci Bioeng 2025:S1389-1723(25)00106-9. [PMID: 40413115 DOI: 10.1016/j.jbiosc.2025.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2025] [Revised: 04/28/2025] [Accepted: 05/01/2025] [Indexed: 05/27/2025]
Abstract
Decreased cell viability resulting from severe nutrient deprivation is a major obstacle in three-dimensional (3D) tissue construction. Therefore, technical improvements that prevent cell death in the core region of cell aggregates are desired for the development of large, thick tissues. We focused on the anti-glycolytic effects of resveratrol (RSV), a polyphenol known as a caloric restriction mimetic, and investigated its cytoprotective effects under glucose-deprived conditions in two-dimensional (2D) and 3D-cell culture systems using rat chondrocytes. In 2D culture, the low-glucose (LG, 0.5 mg/mL) condition caused time- and dose-dependent cell death in chondrocytes, whereas co-treatment with 50 μM RSV significantly restored cell viability under glucose deprivation. In RSV-treated cells, the expression levels of glycolytic genes (GLUT1, PKM, and LDHA) and glucose uptake were significantly downregulated, and phospho-AMPK levels were upregulated, indicating energy stress. RSV treatment restored the expression of extracellular matrix genes (COL1A1 and COL2A1), which were downregulated under the LG condition, and augmented the pro-chondrogenic effect of TGF-β1 and ascorbic acid. In a 3D-culture model, spheroids constructed with RSV-pretreated chondrocytes had a more viable core region than dimethyl-sulfoxide-treated control spheroids. TGF-β-induced cartilage maturation led these spheroids to develop larger and more viable tissues than control spheroids. These results suggested that glycolytic inhibition by RSV decreased chondrocyte glucose usage, thereby preventing cell death caused by glucose deprivation. Our findings provide useful information for improving cell viability under hyponutrition conditions and can be applied to 3D tissue construction.
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Affiliation(s)
- Rui Zhang
- Graduate School of Science and Engineering, Department of Bioscience, Faculty of Life Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan
| | - Keita Kanki
- Graduate School of Science and Engineering, Department of Bioscience, Faculty of Life Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan.
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2
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Banerjee A, Thekkekkara D, Manjula SN, Nair SP, Lalitha MS. Correlation of autophagy and Alzheimer's disease with special emphasis on the role of phosphodiesterase-4. 3 Biotech 2025; 15:139. [PMID: 40292249 PMCID: PMC12018668 DOI: 10.1007/s13205-025-04306-5] [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: 02/14/2025] [Accepted: 04/02/2025] [Indexed: 04/30/2025] Open
Abstract
Autophagy disruption is important in Alzheimer's disease (AD) as it prevents misfolded proteins from being removed, which leads to the accumulation of amyloid plaques and neurofibrillary tangles (NFTs). Restoring autophagy improves neuronal survival and cognitive function, according to experimental models. In AD models, mTOR inhibition and AMPK activation enhance synaptic plasticity and lessen learning deficits. Inhibitors of phosphodiesterase-4 (PDE4) improve cognition and reduce neuroinflammation via altering cyclic adenosine monophosphate (cAMP) transmission. Furthermore, autophagic-lysosomal clearance is encouraged by upregulating transcription factor EB (TFEB), which lessens the pathogenic damage linked to AD. These results point to autophagy modification as a promising therapeutic approach, with the mTOR, AMPK, cAMP, and TFEB pathways being possible targets for drugs. Though much evidence is based on animal studies, these findings provide valuable insights into autophagy's role in AD pathology, offering promising directions for future research and drug development.
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Affiliation(s)
- Aniruddha Banerjee
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysore, Karnataka 570 015 India
| | - Dithu Thekkekkara
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysore, Karnataka 570 015 India
| | - S. N. Manjula
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysore, Karnataka 570 015 India
| | - Salini P. Nair
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysore, Karnataka 570 015 India
| | - Mankala Sree Lalitha
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysore, Karnataka 570 015 India
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3
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Khamis MM, Moselhy SS, Rihan S. Role of trans-resveratrol in ameliorating biochemical and molecular alterations in obese rats induced by a high fructose/fat diet. Sci Rep 2025; 15:7879. [PMID: 40050385 PMCID: PMC11885455 DOI: 10.1038/s41598-025-91027-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 02/18/2025] [Indexed: 03/09/2025] Open
Abstract
We evaluated the effect of trans-resveratrol (RSV) in ameliorating biochemical and molecular alterations in obese Wister male rats fed on high-fat/high-fructose-fed. Male Wister rats were divided into eight groups and fed with either a standard diet (control), high fructose (HF), high fat (HFAT), or a high- fructose high- fat (HF/HFAT) diet and supplemented with RSV (30 mg/kg/day) for 4 weeks. The food intake, body weight, glycemic parameters, lipid profile, oxidative stress were assessed. SIRT1 gene expression, PGC-1α, cyto-c and GLUT-4 were evaluated by qRT-PCR in adipose tissue of normal and obese rats. The body weight gain, serum fasting glucose, insulin, and HOMA-IR values were significantly higher in the HF and HF/HFAT groups than in the HFAT and control groups. Hyperlipidemia was observed in high calorie diets fed rats compared to control group. The levels of total cholesterol, triglycerides and LDL-c were significantly elevated while HDL- c was significantly decreased in HF & HF/HFAT groups compared to HFAT group. The levels of serum malondialdhyde (MDA) and superoxide dismutase (SOD) activity in adipose tissue were elevated in all groups compared to control group, particularly in the groups that were kept on a high fructose diets (HF, HF/HFAT). SIRT-1, PGC-1α, Cyto-c, and GLUT-4 genes levels were significantly down regulated in HF, HFAT & HF/HFAT groups compared to control group. Supplementation of T-RSV restored the alteration in carbohydrates-lipid metabolism as well as oxidative stress and upregulation of SIRT-1, PGC-1α, Cyto-c, and GLUT-4 genes. RSV is a promising treatment in the management of pathologic consequences of obesity from high-calorie diet consumption via molecular alteration of target genes.
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Affiliation(s)
- Marwa Maher Khamis
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Said Salama Moselhy
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
| | - Shaimaa Rihan
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
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4
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Yang X, Han H, Wang S, Teng F, Lv X, Zhang M, Zhang Y, Li W, Zhang M, Chen L, Zhang S. Islet-derived exosomal miR-204 accelerates insulin resistance in skeletal muscle by suppressing sirtuin 1: An in vivo study in a mouse model of high-fat diet-induced obesity. Diabetes Obes Metab 2025; 27:1153-1163. [PMID: 39632777 DOI: 10.1111/dom.16102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Revised: 11/15/2024] [Accepted: 11/15/2024] [Indexed: 12/07/2024]
Abstract
AIMS The interaction between pancreatic islets and skeletal muscle plays a pivotal role in the development of insulin resistance. The present study aimed to elucidate the impact of non-hormonal molecules from islets on the insulin sensitivity of skeletal muscle cells. MATERIALS AND METHODS We developed a mouse model of obesity through a high-fat diet, assessing glucose tolerance and conducting miRNA sequencing on skeletal muscle samples. An in vitro model was established by treating cells with palmitic acid, and exosomes in the supernatant were characterized using scanning electron microscopy and CD63 expression analysis. Intracellular miR-204-5p levels were quantified by RT-PCR. RESULTS Our in vivo model demonstrated a robust correlation between miR-204-5p level alterations and obesity-induced insulin resistance. Elevated fatty acid levels were observed to increase miR-204-5p in both skeletal muscle and islets. In cellular studies, palmitic acid increased miR-204-5p in MIN-6 islet β-cells but not in C2C12 skeletal muscle cells. Exosomes containing miR-204-5p, secreted by palmitic acid-treated MIN6 cells, were identified through morphological examination, immunoblotting for the exosomal marker CD63, and intraexosomal miR-204-5p level measurement. C2C12 cells were shown to uptake islet-derived miR-204-5p exosomes, as evidenced by the uptake of Exo-Red labeled exosomes. TargetScan analysis identified a highly conserved binding site for miR-204-5p in the 3' UTR of Sirt mRNA. Functional studies indicated that miR-204-5p overexpression reduced glucose consumption and uptake in C2C12 cells, decreased Sirt expression, and impaired insulin signaling, as evidenced by reduced Akt phosphorylation and membrane Glut4 levels. CONCLUSIONS Our findings reveal that miR-204-5p contributes to the development of insulin resistance in obesity and acts as a signaling molecule in the crosstalk between pancreatic islets and skeletal muscle.
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Affiliation(s)
- Xuehan Yang
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China
| | - Hao Han
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China
| | - Sushan Wang
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China
| | - Fei Teng
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China
| | - Xiaoyan Lv
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China
- Department of Clinical Laboratory, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Meishuang Zhang
- Department of Pharmacology, School of Nursing, Jilin University, Changchun, Jilin, China
| | - Ying Zhang
- Department of Neurology and Neuroscience Center, First Hospital of Jilin University, Changchun, China
| | - Wei Li
- College of Life Sciences, Jilin Agricultural University, Changchun, Jilin, China
| | - Ming Zhang
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China
| | - Li Chen
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China
- Department of Pharmacology, School of Nursing, Jilin University, Changchun, Jilin, China
| | - Siwei Zhang
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China
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Strunz CMC, Roggerio A, Cruz PL, Benvenuti LA, Irigoyen MC, Mansur ADP. Resveratrol Attenuates Fibrosis and Alters Signaling Pathways in Diabetic Cardiac and Skeletal Muscles and Adipose Tissue Without Reversing Structural Damage. Int J Mol Sci 2025; 26:1672. [PMID: 40004135 PMCID: PMC11855909 DOI: 10.3390/ijms26041672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 02/12/2025] [Accepted: 02/13/2025] [Indexed: 02/27/2025] Open
Abstract
Resveratrol (RSV) improves metabolic functions, but its tissue-specific effects on diabetes remain unclear. This study investigated RSV's impact on molecular pathways in an experimental model of diabetes in cardiac and skeletal muscles and adipose tissue. Wistar rats were assigned to control (C), control treated with RSV (RC), diabetic (D), and diabetic treated with RSV (RD). Diabetes was induced using streptozotocin and nicotinamide, and RSV was administered for six weeks. In diabetic rats, RSV treatment significantly reduced collagen accumulation in cardiac and skeletal muscle tissues compared to untreated diabetic controls, although it did not restore muscle mass. Adipose tissue in diabetic rats exhibited a significant reduction of 3.4 times in collagen levels following RSV treatment. However, this reduction was not associated with any measurable improvement in tissue function. In cardiac tissue, RSV downregulated phosphorylated protein kinase B (AKT)/AKT and phosphorylated ribosomal protein S6 (rpS6)/rpS6 while mammalian target of rapamycin (mTOR) activity remained unchanged. In skeletal muscle, RSV suppressed rpS6 phosphorylation without affecting (mTOR) signaling. RSV enhanced mTOR and Beclin-1 expression in adipose tissue, though metabolic dysfunction persisted. RSV reduced receptors for advanced glycation end-product expression in all tissues, indicating the modulation of hyperglycemia-driven pathways. RSV improved fibrosis and signaling pathways but failed to reverse abnormal tissue growth patterns, including cardiac hypertrophy, skeletal muscle atrophy, and adipose tissue atrophy.
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Affiliation(s)
- Célia Maria Cássaro Strunz
- Laboratório de Análises Clínicas, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, SP, Brazil; (A.R.); (M.C.I.)
| | - Alessandra Roggerio
- Laboratório de Análises Clínicas, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, SP, Brazil; (A.R.); (M.C.I.)
| | - Paula Lázara Cruz
- Laboratório de Hipertensão Experimental, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, SP, Brazil;
| | - Luiz Alberto Benvenuti
- Laboratório de Anatomia Patológica, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, SP, Brazil;
| | - Maria Cláudia Irigoyen
- Laboratório de Análises Clínicas, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, SP, Brazil; (A.R.); (M.C.I.)
| | - Antonio de Padua Mansur
- Serviço de Prevenção, Cardiopatia na Mulher e Reabilitação Cardiovascular, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, SP, Brazil;
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6
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Li M, Ding L, Cao L, Zhang Z, Li X, Li Z, Xia Q, Yin K, Song S, Wang Z, Du H, Zhao D, Li X, Wang Z. Natural products targeting AMPK signaling pathway therapy, diabetes mellitus and its complications. Front Pharmacol 2025; 16:1534634. [PMID: 39963239 PMCID: PMC11830733 DOI: 10.3389/fphar.2025.1534634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Accepted: 01/15/2025] [Indexed: 02/20/2025] Open
Abstract
Diabetes mellitus (DM) ranks among the most prevalent chronic metabolic diseases, characterized primarily by a persistent elevation in blood glucose levels. This condition typically stems from either insufficient insulin secretion or a functional defect in the insulin itself. Clinically, diabetes is primarily classified into type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), with T2DM comprising nearly 90% of all diagnosed cases. Notably, the global incidence of T2DM has surged dramatically over recent decades. The adenylate-activated protein kinase (AMPK) signaling pathway is crucial in regulating cellular energy metabolism, marking it as a significant therapeutic target for diabetes and related complications. Natural products, characterized by their diverse origins, multifaceted bioactivities, and relative safety, hold considerable promise in modulating the AMPK pathway. This review article explores the advances in research on natural products that target the AMPK signaling pathway, aiming to inform the development of innovative antidiabetic therapies.
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Affiliation(s)
- Min Li
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efcacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Jilin, China
| | - Lu Ding
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efcacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Jilin, China
- Research Center of Traditional Chinese Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Liyuan Cao
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efcacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Jilin, China
| | - Zepeng Zhang
- Research Center of Traditional Chinese Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Xueyan Li
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efcacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Jilin, China
| | - Zirui Li
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efcacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Jilin, China
| | - Qinjing Xia
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efcacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Jilin, China
| | - Kai Yin
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efcacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Jilin, China
| | - Siyu Song
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efcacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Jilin, China
| | - Zihan Wang
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efcacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Jilin, China
| | - Haijian Du
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efcacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Jilin, China
| | - Daqing Zhao
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efcacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Jilin, China
| | - Xiangyan Li
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efcacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Jilin, China
| | - Zeyu Wang
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efcacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Jilin, China
- Research Center of Traditional Chinese Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
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7
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Cai Y, Chen Q. Resveratrol: A Narrative Review Regarding Its Mechanisms in Mitigating Obesity-Associated Metabolic Disorders. Phytother Res 2025; 39:999-1019. [PMID: 39715730 DOI: 10.1002/ptr.8416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 12/04/2024] [Accepted: 12/07/2024] [Indexed: 12/25/2024]
Abstract
Resveratrol (RSV) is a naturally occurring astragalus-like polyphenolic compound with remarkable weight loss properties. However, the mechanism of RSV in treating obesity is unclear. In this narrative review, we explored electronic databases (PubMed) for research articles from 2021 to the present using the keywords "resveratrol" and "obesity". This article explores the mechanisms involved in the alleviation of obesity-related metabolic disorders by RSV. RSV affects obesity by modulating mitochondrial function, insulin signaling, and gut microbiota, regulating lipid metabolism, inhibiting oxidative stress, and regulating epigenetic regulation. Administering RSV to pregnant animals exhibits maternal and first-generation offspring benefits, and RSV administration to lactating animals has long-term benefits, which involve the epigenetic modulations by RSV. A comprehensive understanding of the epigenetic mechanisms of RSV regulation could help in developing drugs suitable for pregnancy preparation groups, pregnant women, and nursing infants.
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Affiliation(s)
- Yichen Cai
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qiu Chen
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
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8
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Bonato A, Raparelli G, Caruso M. Molecular pathways involved in the control of contractile and metabolic properties of skeletal muscle fibers as potential therapeutic targets for Duchenne muscular dystrophy. Front Physiol 2024; 15:1496870. [PMID: 39717824 PMCID: PMC11663947 DOI: 10.3389/fphys.2024.1496870] [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: 09/15/2024] [Accepted: 11/25/2024] [Indexed: 12/25/2024] Open
Abstract
Duchenne muscular dystrophy (DMD) is caused by mutations in the gene encoding dystrophin, a subsarcolemmal protein whose absence results in increased susceptibility of the muscle fiber membrane to contraction-induced injury. This results in increased calcium influx, oxidative stress, and mitochondrial dysfunction, leading to chronic inflammation, myofiber degeneration, and reduced muscle regenerative capacity. Fast glycolytic muscle fibers have been shown to be more vulnerable to mechanical stress than slow oxidative fibers in both DMD patients and DMD mouse models. Therefore, remodeling skeletal muscle toward a slower, more oxidative phenotype may represent a relevant therapeutic approach to protect dystrophic muscles from deterioration and improve the effectiveness of gene and cell-based therapies. The resistance of slow, oxidative myofibers to DMD pathology is attributed, in part, to their higher expression of Utrophin; there are, however, other characteristics of slow, oxidative fibers that might contribute to their enhanced resistance to injury, including reduced contractile speed, resistance to fatigue, increased capillary density, higher mitochondrial activity, decreased cellular energy requirements. This review focuses on signaling pathways and regulatory factors whose genetic or pharmacologic modulation has been shown to ameliorate the dystrophic pathology in preclinical models of DMD while promoting skeletal muscle fiber transition towards a slower more oxidative phenotype.
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Affiliation(s)
| | | | - Maurizia Caruso
- Institute of Biochemistry and Cell Biology, National Research Council (CNR), Monterotondo (RM), Italy
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9
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Zhuang H, Zhang X, Wu S, Yong P, Yan H. Opportunities and challenges of foodborne polyphenols applied to anti-aging health foods. Food Sci Biotechnol 2024; 33:3445-3461. [PMID: 39493397 PMCID: PMC11525373 DOI: 10.1007/s10068-024-01686-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 07/27/2024] [Accepted: 08/12/2024] [Indexed: 11/05/2024] Open
Abstract
Abstract With the increasing proportion of the global aging population, aging mechanisms and anti-aging strategies become hot topics. Nonetheless, the safety of non-natural anti-aging active molecule and the changes in physiological function that occur during aging have not been clarified. There is therefore a need to develop safer pharmaceutical interventions for anti-aging. Numerous types of research have shown that food-derived biomolecules are of great interest due to their unique contribution to anti-aging safety issues and the prevention of degenerative diseases. Among these, polyphenolic organic compounds are widely used in anti-aging research for their ability to mitigate the physiological functional changes that occur during aging. The mechanisms include the free radical theory, immune aging theory, cellular autophagy theory, epigenetic modification theory, gut microbial effects on aging theory, telomere shortening theory, etc. This review elucidates the mechanisms underlying the anti-aging effects of polyphenols found in food-derived bioactive molecules, while also addressing the challenges associated with anti-aging pharmaceuticals. The review concludes by offering insights into the current landscape of anti-aging active molecule research, aiming to serve as a valuable resource for further scholarly inquiry. Graphical abstract
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Affiliation(s)
- Hong Zhuang
- College of Food Science and Engineering, Jilin University, Changchun, 130062 Jilin China
| | - Xiaoliang Zhang
- College of Food Science and Engineering, Jilin University, Changchun, 130062 Jilin China
| | - Sijia Wu
- College of Food Science and Engineering, Jilin University, Changchun, 130062 Jilin China
| | - Pang Yong
- College of Food Science and Engineering, Jilin University, Changchun, 130062 Jilin China
| | - Haiyang Yan
- College of Food Science and Engineering, Jilin University, Changchun, 130062 Jilin China
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10
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Ren J, Xiang B, Xueling L, Han X, Yang Z, Zhang M, Zhang Y. Molecular mechanisms of mitochondrial homeostasis regulation in neurons and possible therapeutic approaches for Alzheimer's disease. Heliyon 2024; 10:e36470. [PMID: 39281517 PMCID: PMC11401100 DOI: 10.1016/j.heliyon.2024.e36470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Revised: 08/09/2024] [Accepted: 08/15/2024] [Indexed: 09/18/2024] Open
Abstract
Alzheimer's disease (AD) is a neurological disease with memory loss and cognitive decline, which affects a large proportion of the aging population. Regrettably, there are no drug to reverse or cure AD and drug development for the primary theory of amyloid beta deposition has mostly failed. Therefore, there is an urgent need to investigate novel strategies for preventing AD. Recent studies demonstrate that imbalance of mitochondrial homeostasis is a driver in Aβ accumulation, which can lead to the occurrence and deterioration of cognitive impairment in AD patients. This suggests that regulating neuronal mitochondrial homeostasis may be a new strategy for AD. We summarize the importance of mitochondrial homeostasis in AD neuron and its regulatory mechanisms in this review. In addition, we summarize the results of studies indicating mitochondrial dysfunction in AD subjects, including impaired mitochondrial energy production, oxidative stress, imbalance of mitochondrial protein homeostasis, imbalance of fusion and fission, imbalance of neuronal mitochondrial biogenesis and autophagy, and altered mitochondrial motility, in hope of providing possible therapeutic approaches for AD.
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Affiliation(s)
- Jiale Ren
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Beibei Xiang
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Lin Xueling
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiaolu Han
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Zhen Yang
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Mixia Zhang
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yanjun Zhang
- Medical Experiment Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
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11
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Trelford CB, Shepherd TG. LKB1 biology: assessing the therapeutic relevancy of LKB1 inhibitors. Cell Commun Signal 2024; 22:310. [PMID: 38844908 PMCID: PMC11155146 DOI: 10.1186/s12964-024-01689-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 05/28/2024] [Indexed: 06/10/2024] Open
Abstract
Liver Kinase B1 (LKB1), encoded by Serine-Threonine Kinase 11 (STK11), is a master kinase that regulates cell migration, polarity, proliferation, and metabolism through downstream adenosine monophosphate-activated protein kinase (AMPK) and AMPK-related kinase signalling. Since genetic screens identified STK11 mutations in Peutz-Jeghers Syndrome, STK11 mutants have been implicated in tumourigenesis labelling it as a tumour suppressor. In support of this, several compounds reduce tumour burden through upregulating LKB1 signalling, and LKB1-AMPK agonists are cytotoxic to tumour cells. However, in certain contexts, its role in cancer is paradoxical as LKB1 promotes tumour cell survival by mediating resistance against metabolic and oxidative stressors. LKB1 deficiency has also enhanced the selectivity and cytotoxicity of several cancer therapies. Taken together, there is a need to develop LKB1-specific pharmacological compounds, but prior to developing LKB1 inhibitors, further work is needed to understand LKB1 activity and regulation. However, investigating LKB1 activity is strenuous as cell/tissue type, mutations to the LKB1 signalling pathway, STE-20-related kinase adaptor protein (STRAD) binding, Mouse protein 25-STRAD binding, splicing variants, nucleocytoplasmic shuttling, post-translational modifications, and kinase conformation impact the functional status of LKB1. For these reasons, guidelines to standardize experimental strategies to study LKB1 activity, associate proteins, spliced isoforms, post-translational modifications, and regulation are of upmost importance to the development of LKB1-specific therapies. Therefore, to assess the therapeutic relevancy of LKB1 inhibitors, this review summarizes the importance of LKB1 in cell physiology, highlights contributors to LKB1 activation, and outlines the benefits and risks associated with targeting LKB1.
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Affiliation(s)
- Charles B Trelford
- The Mary &, John Knight Translational Ovarian Cancer Research Unit, London Regional Cancer Program, 790 Commissioners Road East, Room A4‑921, London, ON, N6A 4L6, Canada.
- Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
| | - Trevor G Shepherd
- The Mary &, John Knight Translational Ovarian Cancer Research Unit, London Regional Cancer Program, 790 Commissioners Road East, Room A4‑921, London, ON, N6A 4L6, Canada
- Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
- Department of Oncology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
- Department of Obstetrics and Gynaecology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
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12
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Gibril BAA, Xiong X, Chai X, Xu Q, Gong J, Xu J. Unlocking the Nexus of Sirtuins: A Comprehensive Review of Their Role in Skeletal Muscle Metabolism, Development, and Disorders. Int J Biol Sci 2024; 20:3219-3235. [PMID: 38904020 PMCID: PMC11186354 DOI: 10.7150/ijbs.96885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 05/23/2024] [Indexed: 06/22/2024] Open
Abstract
The sirtuins constitute a group of histone deacetylases reliant on NAD+ for their activity that have gained recognition for their critical roles as regulators of numerous biological processes. These enzymes have various functions in skeletal muscle biology, including development, metabolism, and the body's response to disease. This comprehensive review seeks to clarify sirtuins' complex role in skeletal muscle metabolism, including glucose uptake, fatty acid oxidation, mitochondrial dynamics, autophagy regulation, and exercise adaptations. It also examines their critical roles in developing skeletal muscle, including myogenesis, the determination of muscle fiber type, regeneration, and hypertrophic responses. Moreover, it sheds light on the therapeutic potential of sirtuins by examining their impact on a range of skeletal muscle disorders. By integrating findings from various studies, this review outlines the context of sirtuin-mediated regulation in skeletal muscle, highlighting their importance and possible consequences for health and disease.
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Affiliation(s)
| | | | | | | | | | - Jiguo Xu
- Jiangxi Provincial Key Laboratory of Poultry Genetic Improvement, Institute of Biological Technology, Nanchang Normal University, Nanchang, 330032, China
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Abstract
Obesity is a severe health problem worldwide due to its association with various adverse health consequences. The present study aims to evaluate the anti-obesity effects of resveratrol, as a natural polyphenol, on the 3T3-L1 adipocytes. PubMed, Scopus, ScienceDirect, Web of Sciences, and Google Scholar databases were searched up to March 2022 using relevant keywords. All original articles, written in English, evaluating the anti-obesity effects of resveratrol on the 3T3-L1 adipocytes were eligible for this review. Initially, 4361 records were found in the electronic search databases. After removing duplicates and irrelevant studies according to the title and abstract, the full text of the 51 articles was critically screened and 38 in vitro studies were included in this review. Except for one case, all of these studies reported that different doses (ranged 1-200 μM) of resveratrol treatment have anti-obesity effects on 3T3L1 adipocytes through various mechanisms such as induction of apoptosis, a decrease of fat accumulation and adipogenesis, promotion of white adipocytes browning, inhibition of preadipocyte proliferation and consequent differentiation, and up-regulation of miRNA that involved in the antiadipogenic and triacylglycerol metabolism in white adipose tissue. The findings indicate that resveratrol has anti-obesity effects. Therefore, resveratrol treatment could be used to prevent and treat obesity and its related disorders. Well-designed randomized clinical trials with different doses of resveratrol are recommended to be performed on obese subjects.
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Affiliation(s)
- Roghayeh Molani-Gol
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Nutrition Research Center, Department of Community Nutrition, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Rafraf
- Nutrition Research Center, Department of Community Nutrition, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
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14
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Koushki M, Farahani M, Yekta RF, Frazizadeh N, Bahari P, Parsamanesh N, Chiti H, Chahkandi S, Fridoni M, Amiri-Dashatan N. Potential role of resveratrol in prevention and therapy of diabetic complications: a critical review. Food Nutr Res 2024; 68:9731. [PMID: 38716357 PMCID: PMC11075469 DOI: 10.29219/fnr.v68.9731] [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: 05/23/2023] [Revised: 08/10/2023] [Accepted: 10/09/2023] [Indexed: 01/03/2025] Open
Abstract
BACKGROUND Diabetes mellitus (DM) is a category of metabolic conditions affecting about 5% of people worldwide. High mortality associated with DM is mostly due to its severe clinical complications, including diabetic nephropathy, retinopathy, neuropathy, and cardiomyopathy. Resveratrol (RSV) is a natural, biologically active polyphenol known to have various health-promoting effects in animal models and humans. OBJECTIVE In this review, we have reviewed the preventive and therapeutic role of RSV on diabetes complications with emphasis on its molecular mechanisms of action. METHODS To prepare this review, all the basic and clinical available literatures regarding this topic were gathered through electronic databases, including PubMed, Web of Science, Scopus, and Google Scholar. Therefore, we summarized previous studies that have evaluated the effects of RSV on diabetic complications and their mechanisms. Only English language studies published up to January 2023 were included in this review. RESULTS RSV improves glucose homeostasis, decreases insulin resistance, induces autophagy, regulates lipid metabolism, protects pancreatic β-cells, ameliorates metabolic disorders, and increases the GLUT4 expression. These effects induced by RSV are strongly associated with ability of this polyphenol agent to elevation expression/activity of AMP-activated protein kinase and Sirtuin 1 in various organs of diabetic subjects, which leads to prevention and therapy of diabetic complications. In addition, antioxidant and anti-inflammatory properties of RSV were reported to be involved in its action in diabetic complications, such as retinopathy and nephropathy. CONCLUSION RSV is a promising compound for improving diabetic complications. However, the exact antidiabetic mechanisms of RSV need to be further investigated.
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Affiliation(s)
- Mehdi Koushki
- Department of Clinical Biochemistry, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Masoumeh Farahani
- Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Naghmeh Frazizadeh
- Department of Clinical Biochemistry, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Parisa Bahari
- Department of Clinical Biochemistry, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Negin Parsamanesh
- Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Hossein Chiti
- Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Somayeh Chahkandi
- Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mohammadjavad Fridoni
- Department of Anatomy, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Nasrin Amiri-Dashatan
- Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
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15
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Liao Z, Cai X, Zheng Y, Lin J, Yang X, Lin W, Zhang Y, He X, Liu C. Sirtuin 1 in osteoarthritis: Perspectives on regulating glucose metabolism. Pharmacol Res 2024; 202:107141. [PMID: 38490314 DOI: 10.1016/j.phrs.2024.107141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Revised: 03/03/2024] [Accepted: 03/11/2024] [Indexed: 03/17/2024]
Abstract
Osteoarthritis (OA) is a degenerative disease characterised by articular cartilage destruction, and its complex aetiology contributes to suboptimal clinical treatment outcomes. A close association exists between glucose metabolism dysregulation and OA pathogenesis. Owing to the unique environment of low oxygen and glucose concentrations, chondrocytes rely heavily on their glycolytic capacity, exhibiting distinct spatiotemporal differences. However, under pathological stimulation, chondrocytes undergo excessive glycolytic activity while mitochondrial respiration and other branches of glucose metabolism are compromised. This metabolic change induces cartilage degeneration by reprogramming the inflammatory responses. Sirtuins, a highly conserved family of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, regulate glucose metabolism in response to energy fluctuations in different cellular compartments，alleviating metabolic stress. SIRT1, the most extensively studied sirtuin, participates in maintaining glucose homeostasis in almost all key metabolic tissues. While actively contributing to the OA progression and displaying diverse biological effects in cartilage protection, SIRT1's role in regulating glucose metabolism in chondrocytes has not received sufficient attention. This review focuses on discussing the beneficial role of SIRT1 in OA progression from a metabolic regulation perspective based on elucidating the primary characteristics of chondrocyte glucose metabolism. We also summarise the potential mechanisms and therapeutic strategies targeting SIRT1 in chondrocytes to guide clinical practice and explore novel therapeutic directions.
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Affiliation(s)
- Zhihao Liao
- Department of Orthodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, 366, Jiangnan Avenue South, Guangzhou 510280, China
| | - Xuepei Cai
- Department of Pediatric Dentistry, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, China
| | - Yifan Zheng
- Department of Orthodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, 366, Jiangnan Avenue South, Guangzhou 510280, China
| | - Jiayu Lin
- Department of Orthodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, 366, Jiangnan Avenue South, Guangzhou 510280, China
| | - Xia Yang
- Department of Orthodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, 366, Jiangnan Avenue South, Guangzhou 510280, China
| | - Weiyin Lin
- Department of Orthodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, 366, Jiangnan Avenue South, Guangzhou 510280, China
| | - Ying Zhang
- Department of Orthodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, 366, Jiangnan Avenue South, Guangzhou 510280, China
| | - Xin He
- Department of Orthodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, 366, Jiangnan Avenue South, Guangzhou 510280, China
| | - Chufeng Liu
- Department of Orthodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, 366, Jiangnan Avenue South, Guangzhou 510280, China.
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16
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Komorowska J, Wątroba M, Bednarzak M, Grabowska AD, Szukiewicz D. Anti-Inflammatory Action of Resveratrol in the Central Nervous System in Relation to Glucose Concentration-An In Vitro Study on a Blood-Brain Barrier Model. Int J Mol Sci 2024; 25:3110. [PMID: 38542084 PMCID: PMC10970537 DOI: 10.3390/ijms25063110] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 03/05/2024] [Accepted: 03/06/2024] [Indexed: 01/03/2025] Open
Abstract
Unbalanced blood glucose levels may cause inflammation within the central nervous system (CNS). This effect can be reversed by the action of a natural neuroprotective compound, resveratrol (RSV). The study aimed to investigate the anti-inflammatory effect of RSV on astrocyte cytokine profiles within an in vitro model of the blood-brain barrier (BBB) under varying glucose concentrations (2.2, 5.0, and 25.0 mmol/L), corresponding to hypo-, normo-, and hyperglycemia. The model included co-cultures of astrocytes (brain compartment, BC) and endothelial cells (microvascular compartment, MC), separated by 0.4 µm wide pores. Subsequent exposure to 0.2 μM LPS in the brain compartment (BC) and 50 μM RSV in the microvascular compartment (MC) of each well was carried out. Cytokine levels (IL-1 α, IL-1 β, IL-2, IL-4, IL-6, IL-8) in the BC were assessed using a Multi-Analyte ELISArray Kit before and after the addition of LPS and RSV. Statistical analysis was performed to determine significance levels. The results demonstrated that RSV reduced the concentration of all studied cytokines in the BC, regardless of glucose levels, with the most substantial decrease observed under normoglycemic conditions. Additionally, the concentration of RSV in the BC was highest under normoglycemic conditions compared to hypo- and hyperglycemia. These findings confirm that administration of RSV in the MC exerts anti-inflammatory effects within the BC, particularly under normoglycemia-simulating conditions. Further in vivo studies, including animal and human research, are warranted to elucidate the bioavailability of RSV within the central nervous system (CNS).
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Affiliation(s)
| | | | | | | | - Dariusz Szukiewicz
- Laboratory of the Blood-Brain Barrier, Department of Biophysics, Physiology and Pathophysiology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland; (J.K.); (M.W.); (A.D.G.)
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17
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Park S, Jevtovic F, Krassovskaia PM, Chaves AB, Zheng D, Treebak JT, Houmard JA. Effect of resveratrol on insulin action in primary myotubes from lean individuals and individuals with severe obesity. Am J Physiol Endocrinol Metab 2024; 326:E398-E406. [PMID: 38324260 PMCID: PMC11193525 DOI: 10.1152/ajpendo.00299.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 01/29/2024] [Accepted: 01/31/2024] [Indexed: 02/08/2024]
Abstract
Resveratrol, a natural polyphenol compound contained in numerous plants, has been proposed as a treatment for obesity-related disease processes such as insulin resistance. However, in humans there are conflicting results concerning the efficacy of resveratrol in improving insulin action; the purpose of the present study was to determine whether obesity status (lean, severely obese) affects the response to resveratrol in human skeletal muscle. Primary skeletal muscle cells were derived from biopsies obtained from age-matched lean and insulin-resistant women with severe obesity and incubated with resveratrol (1 µM) for 24 h. Insulin-stimulated glucose oxidation and incorporation into glycogen, insulin signal transduction, and energy-sensitive protein targets [AMP-activated protein kinase (AMPK), Sirt1, and PGC1α] were analyzed. Insulin-stimulated glycogen synthesis, glucose oxidation, and AMPK phosphorylation increased with resveratrol incubation compared with the nonresveratrol conditions (main treatment effect for resveratrol). Resveratrol further increased IRS1, Akt, and TBC1D4 insulin-stimulated phosphorylation and SIRT1 content in myotubes from lean women, but not in women with severe obesity. Resveratrol improves insulin action in primary human skeletal myotubes derived from lean women and women with severe obesity. In women with obesity, these improvements may be associated with enhanced AMPK phosphorylation with resveratrol treatment.NEW & NOTEWORTHY A physiologically relevant dose of resveratrol increases insulin-stimulated glucose oxidation and glycogen synthesis in myotubes from individuals with severe obesity. Furthermore, resveratrol improved insulin signal transduction in myotubes from lean individuals but not from individuals with obesity. Activation of AMPK plays a role in resveratrol-induced improvements in glucose metabolism in individuals with severe obesity.
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Affiliation(s)
- Sanghee Park
- Human Performance Laboratory, East Carolina University, Greenville, North Carolina, United States
- Department of Kinesiology, East Carolina University, Greenville, North Carolina, United States
- East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, United States
- Department of Exercise Rehabilitation, Gachon University, Incheon, Republic of Korea
| | - Filip Jevtovic
- Human Performance Laboratory, East Carolina University, Greenville, North Carolina, United States
- Department of Kinesiology, East Carolina University, Greenville, North Carolina, United States
- East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, United States
| | - Polina M Krassovskaia
- Human Performance Laboratory, East Carolina University, Greenville, North Carolina, United States
- Department of Kinesiology, East Carolina University, Greenville, North Carolina, United States
- East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, United States
| | - Alec B Chaves
- Human Performance Laboratory, East Carolina University, Greenville, North Carolina, United States
- Department of Kinesiology, East Carolina University, Greenville, North Carolina, United States
- East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, United States
| | - Donghai Zheng
- Human Performance Laboratory, East Carolina University, Greenville, North Carolina, United States
- Department of Kinesiology, East Carolina University, Greenville, North Carolina, United States
- East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, United States
| | - Jonas T Treebak
- Section of Integrative Physiology, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Joseph A Houmard
- Human Performance Laboratory, East Carolina University, Greenville, North Carolina, United States
- Department of Kinesiology, East Carolina University, Greenville, North Carolina, United States
- East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, United States
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18
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Yin X, Guo Z, Song C. AMPK, a key molecule regulating aging-related myocardial ischemia-reperfusion injury. Mol Biol Rep 2024; 51:257. [PMID: 38302614 DOI: 10.1007/s11033-023-09050-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 10/10/2023] [Indexed: 02/03/2024]
Abstract
Aging leads to the threat of more diseases to the biological anatomical structure and the decline of disease resistance, increasing the incidence and mortality of myocardial ischemia-reperfusion injury (MI/RI). Moreover, MI/RI promotes damage to an aging heart. Notably, 5'-adenosine monophosphate-activated protein kinase (AMPK) regulates cellular energy metabolism, stress response, and protein metabolism, participates in aging-related signaling pathways, and plays an essential role in ischemia-reperfusion (I/R) injury diseases. This study aims to introduce the aging theory, summarize the interaction between aging and MI/RI, and describe the crosstalk of AMPK in aging and MI/RI. We show how AMPK can offer protective effects against age-related stressors, lifestyle factors such as alcohol consumption and smoking, and hypertension. We also review some of the clinical prospects for the development of interventions that harness the effect of AMPK to treat MI/RI and other age-related cardiovascular diseases.
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Affiliation(s)
- Xiaorui Yin
- Department of Cardiology, Second Hospital of Jilin University, No.218 Ziqiang Street, Changchun, 130041, China
| | - Ziyuan Guo
- Department of Cardiology, Second Hospital of Jilin University, No.218 Ziqiang Street, Changchun, 130041, China
| | - Chunli Song
- Department of Cardiology, Second Hospital of Jilin University, No.218 Ziqiang Street, Changchun, 130041, China.
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Kaffe D, Kaplanis SI, Karagogeos D. The Roles of Caloric Restriction Mimetics in Central Nervous System Demyelination and Remyelination. Curr Issues Mol Biol 2023; 45:9526-9548. [PMID: 38132442 PMCID: PMC10742427 DOI: 10.3390/cimb45120596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 11/16/2023] [Accepted: 11/22/2023] [Indexed: 12/23/2023] Open
Abstract
The dysfunction of myelinating glial cells, the oligodendrocytes, within the central nervous system (CNS) can result in the disruption of myelin, the lipid-rich multi-layered membrane structure that surrounds most vertebrate axons. This leads to axonal degeneration and motor/cognitive impairments. In response to demyelination in the CNS, the formation of new myelin sheaths occurs through the homeostatic process of remyelination, facilitated by the differentiation of newly formed oligodendrocytes. Apart from oligodendrocytes, the two other main glial cell types of the CNS, microglia and astrocytes, play a pivotal role in remyelination. Following a demyelination insult, microglia can phagocytose myelin debris, thus permitting remyelination, while the developing neuroinflammation in the demyelinated region triggers the activation of astrocytes. Modulating the profile of glial cells can enhance the likelihood of successful remyelination. In this context, recent studies have implicated autophagy as a pivotal pathway in glial cells, playing a significant role in both their maturation and the maintenance of myelin. In this Review, we examine the role of substances capable of modulating the autophagic machinery within the myelinating glial cells of the CNS. Such substances, called caloric restriction mimetics, have been shown to decelerate the aging process by mitigating age-related ailments, with their mechanisms of action intricately linked to the induction of autophagic processes.
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Affiliation(s)
- Despoina Kaffe
- Department of Biology, University of Crete, Vassilika Vouton, 70013 Heraklion, Greece;
| | - Stefanos Ioannis Kaplanis
- Department of Basic Science, School of Medicine, University of Crete, Vassilika Vouton, 70013 Heraklion, Greece;
- Institute of Molecular Biology & Biotechnology (IMBB), Foundation for Research and Technology-Hellas (FORTH), Vassilika Vouton, 70013 Heraklion, Greece
| | - Domna Karagogeos
- Department of Basic Science, School of Medicine, University of Crete, Vassilika Vouton, 70013 Heraklion, Greece;
- Institute of Molecular Biology & Biotechnology (IMBB), Foundation for Research and Technology-Hellas (FORTH), Vassilika Vouton, 70013 Heraklion, Greece
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20
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Chen S, Fu Y, Wang T, Chen Z, Zhao P, Huang X, Qiao M, Li T, Song L. Effect of 2'-Fucosyllactose on Beige Adipocyte Formation in 3T3-L1 Adipocytes and C3H10T1/2 Cells. Foods 2023; 12:4137. [PMID: 38002194 PMCID: PMC10670332 DOI: 10.3390/foods12224137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 11/11/2023] [Accepted: 11/14/2023] [Indexed: 11/26/2023] Open
Abstract
2'-Fucosyllactose (2'-FL), the functional oligosaccharide naturally present in milk, has been shown to exert health benefits. This study was aimed to investigate the effect of 2'-fucosyllactose (2'-FL) on the browning of white adipose tissue in 3T3-L1 adipocytes and C3H10T1/2 cells. The results revealed that 2'-FL decreased lipid accumulations with reduced intracellular triglyceride contents in vitro. 2'-FL intervention increased the mitochondria density and the proportion of UCP1-positive cells. The mRNA expressions of the mitochondrial biogenesis-related and browning markers (Cox7a, Cyto C, Tfam, Ucp1, Pgc1α, Prdm16, Cidea, Elovl3, Pparα, CD137, and Tmem26) were increased after 2'-FL intervention to some extent. Similarly, the protein expression of the browning markers, including UCP1, PGC1α, and PRDM16, was up-regulated in the 2'-FL group. Additionally, an adenosine monophosphate-activated protein kinase (AMPK) inhibitor, compound C (1 μM), significantly decreased the induction of thermogenic proteins expressions mediated by 2'-FL, indicating that the 2'-FL-enhanced beige cell formation was partially dependent on the AMPK pathway. In conclusion, 2'-FL effectively promoted the browning of white adipose in vitro.
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Affiliation(s)
- Siru Chen
- Henan Engineering Technology Research Center of Food Processing and Circulation Safety Control, College of Food Science and Technology, Henan Agricultural University, Zhengzhou 450002, China; (S.C.); (Z.C.)
| | - Yankun Fu
- Henan Engineering Technology Research Center of Food Processing and Circulation Safety Control, College of Food Science and Technology, Henan Agricultural University, Zhengzhou 450002, China; (S.C.); (Z.C.)
| | - Tianlin Wang
- Henan Engineering Technology Research Center of Food Processing and Circulation Safety Control, College of Food Science and Technology, Henan Agricultural University, Zhengzhou 450002, China; (S.C.); (Z.C.)
| | - Zhenglin Chen
- Henan Engineering Technology Research Center of Food Processing and Circulation Safety Control, College of Food Science and Technology, Henan Agricultural University, Zhengzhou 450002, China; (S.C.); (Z.C.)
| | - Peijun Zhao
- Henan Engineering Technology Research Center of Food Processing and Circulation Safety Control, College of Food Science and Technology, Henan Agricultural University, Zhengzhou 450002, China; (S.C.); (Z.C.)
| | - Xianqing Huang
- Henan Engineering Technology Research Center of Food Processing and Circulation Safety Control, College of Food Science and Technology, Henan Agricultural University, Zhengzhou 450002, China; (S.C.); (Z.C.)
- Henan Technology Innovation Center of Meat Processing and Research, College of Food Science and Technology, Henan Agricultural University, Zhengzhou 450002, China
| | - Mingwu Qiao
- Henan Engineering Technology Research Center of Food Processing and Circulation Safety Control, College of Food Science and Technology, Henan Agricultural University, Zhengzhou 450002, China; (S.C.); (Z.C.)
- Henan Technology Innovation Center of Meat Processing and Research, College of Food Science and Technology, Henan Agricultural University, Zhengzhou 450002, China
| | - Tiange Li
- Henan Engineering Technology Research Center of Food Processing and Circulation Safety Control, College of Food Science and Technology, Henan Agricultural University, Zhengzhou 450002, China; (S.C.); (Z.C.)
| | - Lianjun Song
- Henan Engineering Technology Research Center of Food Processing and Circulation Safety Control, College of Food Science and Technology, Henan Agricultural University, Zhengzhou 450002, China; (S.C.); (Z.C.)
- Henan Technology Innovation Center of Meat Processing and Research, College of Food Science and Technology, Henan Agricultural University, Zhengzhou 450002, China
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21
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Bahramzadeh A, Bolandnazar K, Meshkani R. Resveratrol as a potential protective compound against skeletal muscle insulin resistance. Heliyon 2023; 9:e21305. [PMID: 38027557 PMCID: PMC10660041 DOI: 10.1016/j.heliyon.2023.e21305] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 10/17/2023] [Accepted: 10/19/2023] [Indexed: 12/01/2023] Open
Abstract
The increasing prevalence of type 2 diabetes has become a major global problem. Insulin resistance has a central role in pathophysiology of type 2 diabetes. Skeletal muscle is responsible for the disposal of most of the glucose under conditions of insulin stimulation, and insulin resistance in skeletal muscle causes dysregulation of glucose homeostasis in the whole body. Despite the current pharmaceutical and non-pharmacological treatment strategies to combat diabetes, there is still a need for new therapeutic agents due to the limitations of the therapeutic agents. Meanwhile, plant polyphenols have attracted the attention of researchers for their use in the treatment of diabetes and have gained popularity. Resveratrol, a stilbenoid polyphenol, exists in various plant sources, and a growing body of evidence suggests its beneficial properties, including antidiabetic activities. The present review aimed to provide a summary of the role of resveratrol in insulin resistance in skeletal muscle and its related mechanisms. To achieve the objectives, by searching the PubMed, Scopus and Web of Science databases, we have summarized the results of all cell culture, animal, and human studies that have investigated the effects of resveratrol in different models on insulin resistance in skeletal muscle.
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Affiliation(s)
- Arash Bahramzadeh
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Kosar Bolandnazar
- Department of Biological Sciences and Technology, Islamic Azad University of Mashhad, Mashhad, Iran
| | - Reza Meshkani
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Li Y, Zhang Y, Deng Q, Mao J, Jia Z, Tang M, Zhang Y, Zhao J, Chen J, Wang Y, Feng Z, Wang X, Du L. Resveratrol reverses Palmitic Acid-induced cow neutrophils apoptosis through shifting glucose metabolism into lipid metabolism via Cav-1/ CPT 1-mediated FAO enhancement. J Steroid Biochem Mol Biol 2023; 233:106363. [PMID: 37454955 DOI: 10.1016/j.jsbmb.2023.106363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Revised: 06/16/2023] [Accepted: 07/11/2023] [Indexed: 07/18/2023]
Abstract
Elevated plasma nonesterified fatty acids (NEFAs) affect neutrophils function and longevity during the periparturient period in dairy cows. Previous research has shown that resveratrol (RSV) may protect cell viability from NEFA-induced damage by regulating energy metabolism. However, it is unclear whether RSV has a protective effect on palmitic acid (PA)-treated neutrophils. The aim of this study was to investigate the molecular regulatory mechanism of the protective effect of RSV on neutrophils. The results showed that treatment with high concentrations of RSV (50 μM, 100 μM) maintained neutrophils activity by inhibiting neutrophils apoptosis (P < 0.05). Further analysis showed that high concentrations of RSV enhanced fatty acid oxidation (FAO) to produce ATP by promoting the expression of CAV1, ACSL-1 and CPT1 (P < 0. 05) while inhibiting glycolysis by suppressing PFK1 activity (P < 0. 05) and reducing glucose transport-related protein (GLUT1/GLUT4) expression by inhibiting glucose uptake (P < 0.05). These results suggest that RSV protects neutrophils from PA-induced apoptosis by regulating energy metabolism. Our results revealed that RSV protects neutrophils from PA-induced apoptosis by shifting glucose metabolism to lipid metabolism. This study tenders to a meaningful understanding of the effects of RSV on neutrophils function in periparturient cows suffering from negative energy balance (NEB).
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Affiliation(s)
- Yansong Li
- College of Animal Science and Technology, Inner Mongolia MINZU University, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Yuming Zhang
- College of Animal Science and Technology, Inner Mongolia MINZU University, Tongliao 028000, Inner Mongolia Autonomous Region, China; Inner Mongolia MINZU University Key Laboratory for Prevention and Control of Herbivorous Livestock Perinatal Diseases, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Qinghua Deng
- College of Animal Science and Technology, Inner Mongolia MINZU University, Tongliao 028000, Inner Mongolia Autonomous Region, China; Inner Mongolia MINZU University Key Laboratory for Prevention and Control of Herbivorous Livestock Perinatal Diseases, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Jingdong Mao
- College of Animal Science and Technology, Inner Mongolia MINZU University, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Zhenwei Jia
- College of Animal Science and Technology, Inner Mongolia MINZU University, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Mingyu Tang
- College of Animal Science and Technology, Inner Mongolia MINZU University, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Yue Zhang
- College of Animal Science and Technology, Inner Mongolia MINZU University, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Junkang Zhao
- College of Animal Science and Technology, Inner Mongolia MINZU University, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Jiaojiao Chen
- College of Animal Science and Technology, Inner Mongolia MINZU University, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Yiru Wang
- College of Animal Science and Technology, Inner Mongolia MINZU University, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Ziying Feng
- College of Animal Science and Technology, Inner Mongolia MINZU University, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Xinbo Wang
- College of Animal Science and Technology, Inner Mongolia MINZU University, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Liyin Du
- College of Animal Science and Technology, Inner Mongolia MINZU University, Tongliao 028000, Inner Mongolia Autonomous Region, China; Inner Mongolia MINZU University Key Laboratory for Prevention and Control of Herbivorous Livestock Perinatal Diseases, Tongliao 028000, Inner Mongolia Autonomous Region, China.
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Grabowska AD, Wątroba M, Witkowska J, Mikulska A, Sepúlveda N, Szukiewicz D. Interplay between Systemic Glycemia and Neuroprotective Activity of Resveratrol in Modulating Astrocyte SIRT1 Response to Neuroinflammation. Int J Mol Sci 2023; 24:11640. [PMID: 37511397 PMCID: PMC10380505 DOI: 10.3390/ijms241411640] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 07/14/2023] [Accepted: 07/17/2023] [Indexed: 07/30/2023] Open
Abstract
The flow of substances between the blood and the central nervous system is precisely regulated by the blood-brain barrier (BBB). Its disruption due to unbalanced blood glucose levels (hyper- and hypoglycemia) occurring in metabolic disorders, such as type 2 diabetes, can lead to neuroinflammation, and increase the risk of developing neurodegenerative diseases. One of the most studied natural anti-diabetic, anti-inflammatory, and neuroprotective compounds is resveratrol (RSV). It activates sirtuin 1 (SIRT1), a key metabolism regulator dependent on cell energy status. The aim of this study was to assess the astrocyte SIRT1 response to neuroinflammation and subsequent RSV treatment, depending on systemic glycemia. For this purpose, we used an optimized in vitro model of the BBB consisting of endothelial cells and astrocytes, representing microvascular and brain compartments (MC and BC), in different glycemic backgrounds. Astrocyte-secreted SIRT1 reached the highest concentration in hypo-, the lowest in normo-, and the lowest in hyperglycemic backgrounds. Lipopolysaccharide (LPS)-induced neuroinflammation caused a substantial decrease in SIRT1 in all glycemic backgrounds, as observed earliest in hyperglycemia. RSV partially counterbalanced the effect of LPS on SIRT1 secretion, most remarkably in normoglycemia. Our results suggest that abnormal glycemic states have a worse prognosis for RSV-therapy effectiveness compared to normoglycemia.
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Affiliation(s)
- Anna D. Grabowska
- Laboratory of the Blood-Brain Barrier, Department of Biophysics, Physiology and Pathophysiology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland; (M.W.); (J.W.); (A.M.); (D.S.)
| | - Mateusz Wątroba
- Laboratory of the Blood-Brain Barrier, Department of Biophysics, Physiology and Pathophysiology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland; (M.W.); (J.W.); (A.M.); (D.S.)
| | - Joanna Witkowska
- Laboratory of the Blood-Brain Barrier, Department of Biophysics, Physiology and Pathophysiology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland; (M.W.); (J.W.); (A.M.); (D.S.)
| | - Agnieszka Mikulska
- Laboratory of the Blood-Brain Barrier, Department of Biophysics, Physiology and Pathophysiology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland; (M.W.); (J.W.); (A.M.); (D.S.)
| | - Nuno Sepúlveda
- Faculty of Mathematics and Information Science, Warsaw University of Technology, Koszykowa 75, 00-662 Warsaw, Poland
- CEAUL—Centro de Estatística e Aplicações da Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal
| | - Dariusz Szukiewicz
- Laboratory of the Blood-Brain Barrier, Department of Biophysics, Physiology and Pathophysiology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland; (M.W.); (J.W.); (A.M.); (D.S.)
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Cavaliere G, Cimmino F, Trinchese G, Catapano A, Petrella L, D'Angelo M, Lucchin L, Mollica MP. From Obesity-Induced Low-Grade Inflammation to Lipotoxicity and Mitochondrial Dysfunction: Altered Multi-Crosstalk between Adipose Tissue and Metabolically Active Organs. Antioxidants (Basel) 2023; 12:1172. [PMID: 37371902 DOI: 10.3390/antiox12061172] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 05/23/2023] [Accepted: 05/27/2023] [Indexed: 06/29/2023] Open
Abstract
Obesity is a major risk factor for several metabolic diseases, including type 2 diabetes, hyperlipidemia, cardiovascular diseases, and brain disorders. Growing evidence suggests the importance of inter-organ metabolic communication for the progression of obesity and the subsequent onset of related disorders. This review provides a broad overview of the pathophysiological processes that from adipose tissue dysfunction leading to altered multi-tissue crosstalk relevant to regulating energy homeostasis and the etiology of obesity. First, a comprehensive description of the role of adipose tissue was reported. Then, attention was turned toward the unhealthy expansion of adipose tissue, low-grade inflammatory state, metabolic inflexibility, and mitochondrial dysfunction as root causes of systemic metabolic alterations. In addition, a short spot was devoted to iron deficiency in obese conditions and the role of the hepcidin-ferroportin relationship in the management of this issue. Finally, different classes of bioactive food components were described with a perspective to enhance their potential preventive and therapeutic use against obesity-related diseases.
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Affiliation(s)
- Gina Cavaliere
- Department of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, Italy
- Centro Servizi Metrologici e Tecnologici Avanzati (CeSMA), Complesso Universitario di Monte Sant'Angelo, 80126 Naples, Italy
| | - Fabiano Cimmino
- Centro Servizi Metrologici e Tecnologici Avanzati (CeSMA), Complesso Universitario di Monte Sant'Angelo, 80126 Naples, Italy
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy
| | - Giovanna Trinchese
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy
| | - Angela Catapano
- Centro Servizi Metrologici e Tecnologici Avanzati (CeSMA), Complesso Universitario di Monte Sant'Angelo, 80126 Naples, Italy
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy
| | - Lidia Petrella
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy
| | - Margherita D'Angelo
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy
| | - Lucio Lucchin
- Dietetics and Clinical Nutrition, Bolzano Health District, 39100 Bolzano, Italy
| | - Maria Pina Mollica
- Centro Servizi Metrologici e Tecnologici Avanzati (CeSMA), Complesso Universitario di Monte Sant'Angelo, 80126 Naples, Italy
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy
- Task Force on Microbiome Studies, University of Naples Federico II, 80138 Naples, Italy
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25
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Naz R, Saqib F, Awadallah S, Wahid M, Latif MF, Iqbal I, Mubarak MS. Food Polyphenols and Type II Diabetes Mellitus: Pharmacology and Mechanisms. Molecules 2023; 28:molecules28103996. [PMID: 37241737 DOI: 10.3390/molecules28103996] [Citation(s) in RCA: 41] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 05/04/2023] [Accepted: 05/07/2023] [Indexed: 05/28/2023] Open
Abstract
Type II diabetes mellitus and its related complications are growing public health problems. Many natural products present in our diet, including polyphenols, can be used in treating and managing type II diabetes mellitus and different diseases, owing to their numerous biological properties. Anthocyanins, flavonols, stilbenes, curcuminoids, hesperidin, hesperetin, naringenin, and phenolic acids are common polyphenols found in blueberries, chokeberries, sea-buckthorn, mulberries, turmeric, citrus fruits, and cereals. These compounds exhibit antidiabetic effects through different pathways. Accordingly, this review presents an overview of the most recent developments in using food polyphenols for managing and treating type II diabetes mellitus, along with various mechanisms. In addition, the present work summarizes the literature about the anti-diabetic effect of food polyphenols and evaluates their potential as complementary or alternative medicines to treat type II diabetes mellitus. Results obtained from this survey show that anthocyanins, flavonols, stilbenes, curcuminoids, and phenolic acids can manage diabetes mellitus by protecting pancreatic β-cells against glucose toxicity, promoting β-cell proliferation, reducing β-cell apoptosis, and inhibiting α-glucosidases or α-amylase. In addition, these phenolic compounds exhibit antioxidant anti-inflammatory activities, modulate carbohydrate and lipid metabolism, optimize oxidative stress, reduce insulin resistance, and stimulate the pancreas to secrete insulin. They also activate insulin signaling and inhibit digestive enzymes, regulate intestinal microbiota, improve adipose tissue metabolism, inhibit glucose absorption, and inhibit the formation of advanced glycation end products. However, insufficient data are available on the effective mechanisms necessary to manage diabetes.
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Affiliation(s)
- Rabia Naz
- Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60000, Pakistan
| | - Fatima Saqib
- Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60000, Pakistan
| | - Samir Awadallah
- Department of Medical Lab Sciences, Faculty of Allied Medical Sciences, Zarqa University, Zarqa 13110, Jordan
| | - Muqeet Wahid
- Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60000, Pakistan
| | - Muhammad Farhaj Latif
- Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60000, Pakistan
| | - Iram Iqbal
- Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60000, Pakistan
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Schirinzi V, Poli C, Berteotti C, Leone A. Browning of Adipocytes: A Potential Therapeutic Approach to Obesity. Nutrients 2023; 15:2229. [PMID: 37432449 DOI: 10.3390/nu15092229] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 05/01/2023] [Accepted: 05/04/2023] [Indexed: 07/12/2023] Open
Abstract
The increasing prevalence of overweight and obesity suggests that current strategies based on diet, exercise, and pharmacological knowledge are not sufficient to tackle this epidemic. Obesity results from a high caloric intake and energy storage, the latter by white adipose tissue (WAT), and when neither are counterbalanced by an equally high energy expenditure. As a matter of fact, current research is focused on developing new strategies to increase energy expenditure. Against this background, brown adipose tissue (BAT), whose importance has recently been re-evaluated via the use of modern positron emission techniques (PET), is receiving a great deal of attention from research institutions worldwide, as its main function is to dissipate energy in the form of heat via a process called thermogenesis. A substantial reduction in BAT occurs during normal growth in humans and hence it is not easily exploitable. In recent years, scientific research has made great strides and investigated strategies that focus on expanding BAT and activating the existing BAT. The present review summarizes current knowledge about the various molecules that can be used to promote white-to-brown adipose tissue conversion and energy expenditure in order to assess the potential role of thermogenic nutraceuticals. This includes tools that could represent, in the future, a valid weapon against the obesity epidemic.
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Affiliation(s)
- Vittoria Schirinzi
- Endocrinology and Care of Diabetes Unit-Azienda Ospedaliero-Universitaria S. Orsola Malpighi, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy
| | - Carolina Poli
- IRCCS-Azienda Ospedaliero-Universitaria S. Orsola Malpighi, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy
| | - Chiara Berteotti
- PRISM Lab, Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy
| | - Alessandro Leone
- International Center for the Assessment of Nutritional Status and the Development of Dietary Intervention Strategies (ICANS-DIS), Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, 20133 Milan, Italy
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27
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Hoca M, Becer E, Vatansever HS. The role of resveratrol in diabetes and obesity associated with insulin resistance. Arch Physiol Biochem 2023; 129:555-561. [PMID: 33719825 DOI: 10.1080/13813455.2021.1893338] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Diabetes mellitus is a significant health problem that is caused by chronic hyperglycaemia as a result of inadequate insulin production or ineffective insulin action in the body. In recent years, many new pharmacological and non-pharmacological therapies have been developed for improving pancreatic insulin secretion and insulin resistance. Resveratrol is a natural and biologically active stilbenoid polyphenol present in various plant species and has the potential to benefit diabetes. The anti-diabetic actions of resveratrol have also been extensively studied in diabetic human and animal models. Moreover, resveratrol might affect insulin sensitivity by regulating visceral fat derivated adipokine levels. The use of resveratrol in combination with anti-diabetic therapies or alone may have significant potential for the management of diabetes mellitus. This review provides an overview of the anti-diabetic action of resveratrol as well as the possible mechanisms that have an effect on insulin secretion and insulin resistance in diabetics.
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Affiliation(s)
- Mustafa Hoca
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Near East University, Nicosia, Cyprus
| | - Eda Becer
- Department of Biochemistry, Faculty of Pharmacy, Near East University, Nicosia, Cyprus
- DESAM Institute, Near East University, Nicosia, Cyprus
| | - Hafize Seda Vatansever
- DESAM Institute, Near East University, Nicosia, Cyprus
- Department of Histology and Embryology, Faculty of Medicine, Manisa Celal Bayar University, Manisa, Turkey
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Li J, Sun Y, Xue C, Yang X, Duan Y, Zhao D, Han J. Nogo-B deficiency suppresses white adipogenesis by regulating β-catenin signaling. Life Sci 2023; 321:121571. [PMID: 36931495 DOI: 10.1016/j.lfs.2023.121571] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 02/21/2023] [Accepted: 03/09/2023] [Indexed: 03/17/2023]
Abstract
AIMS Obesity is a global epidemic around the world. Reticulon-4B (Nogo-B) is an endoplasmic reticulum-resident protein. Our previous work demonstrated that Nogo-B deficiency inhibited obesity and decreased the size of white adipocytes. However, the underlying molecular mechanism of Nogo-B in white adipogenesis remains poorly understood. This study aims to explore the effect of Nogo-B in white adipogenesis, as well as its underlying molecular mechanisms. MAIN METHODS AND FINDINGS The study adopted mouse embryonic fibroblasts (MEFs) and 3T3-L1 preadipocytes to induce white adipogenesis and investigate the effect of Nogo-B on adipogenesis using qRT-PCR, Western blotting, immunofluorescence, lipid quantification, and Oil Red O staining. During white adipogenesis, Nogo-B expression was increased accompanied by upregulation of adipogenic markers. In contrast, Nogo-B deficiency inhibited white adipocyte markers expression and lipid accumulation. Furthermore, the mechanism study showed that Nogo-B deficiency decreased the destruction complex [AXIN1-APC-glycogen synthase kinase 3β (GSK3β)] levels through activating protein kinase B 2 (AKT2), resulting in β-catenin translocating into the nucleus and inhibiting the expression of adipogenic markers. Moreover, Nogo-B deficiency promoted the expression of brown/beige adipocytes markers while improving mitochondrial thermogenesis by activating β-catenin pathway. In addition, Nogo-B deficiency reduced the levels of inflammatory molecules during white adipogenic differentiation. SIGNIFICANCE This study revealed that Nogo-B deficiency inhibited white adipogenesis through AKT2/GSK3β/β-catenin pathway. Meanwhile, Nogo-B deficiency increased the expression of brown/beige adipocyte markers and promoted mitochondrial thermogenesis. In addition, Nogo-B deficiency reduced inflammatory cytokine levels caused by adipogenesis. Collectively, blocking Nogo-B expression may be a potential strategy to suppress white adipogenesis.
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Affiliation(s)
- Jiaqi Li
- College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Nankai University, Tianjin, China
| | - Yuyao Sun
- College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Nankai University, Tianjin, China
| | - Chao Xue
- College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Nankai University, Tianjin, China
| | - Xiaoxiao Yang
- Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China
| | - Yajun Duan
- Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China
| | - Dan Zhao
- Joint National Laboratory for Antibody Drug Engineering, the First Affiliated Hospital of Henan University, Kaifeng, China.
| | - Jihong Han
- College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Nankai University, Tianjin, China; Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China.
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29
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Xia C, Wang G, Chen L, Geng H, Yao J, Bai Z, Deng L. Trans-gnetin H isolated from the seeds of Paeonia species induces autophagy via inhibiting mTORC1 signalling through AMPK activation. Cell Prolif 2023; 56:e13360. [PMID: 36377675 PMCID: PMC9977667 DOI: 10.1111/cpr.13360] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 10/28/2022] [Accepted: 11/02/2022] [Indexed: 11/16/2022] Open
Abstract
Paeonia is a well-known species of ornamental plants, traditional Chinese medicines, and emerging oilseed crops. Apart from nutritional unsaturated fatty acids, the seeds of peonies are rich in stilbenes characterized by their wide-ranging health-promoting properties. Although the typical stilbene resveratrol has been widely reported for its multiple bioactivities, it remains uncertain whether the trimer of resveratrol trans-gnetin H has properties that regulate cancer cell viability, let alone the underlying mechanism. Autophagy regulated by trans-gnetin H was detected by western blotting, immunofluorescence, and quantitative real-time PCR. The effects of trans-gnetin H on apoptosis and proliferation were examined by flow cytometry, colony formation and Cell Counting Kit-8 assays. Trans-gnetin H significantly inhibits cancer cell viability through autophagy by suppressing the phosphorylation of TFEB and promoting its nuclear transport. Mechanistically, trans-gnetin H inhibits the activation and lysosome translocation of mTORC1 by inhibiting the activation of AMPK, indicating that AMPK is a checkpoint for mTORC1 inactivation induced by trans-gnetin H. Moreover, the binding of TSC2 to Rheb was markedly increased in response to trans-gnetin H stimulation. Similarly, trans-gnetin H inhibited the interaction between Raptor and RagC in an AMPK-dependent manner. More importantly, trans-gnetin H-mediated autophagy highly depends on the AMPK-mTORC1 axis. We propose a regulatory mechanism by which trans-gnetin H inhibits the activation of the mTORC1 pathway to control cell autophagy.
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Affiliation(s)
- Chao Xia
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Guoyan Wang
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Lei Chen
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Huijun Geng
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Junhu Yao
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Zhangzhen Bai
- College of Landscape Architecture and Arts, Northwest A&F University, Yangling, Shaanxi, China
| | - Lu Deng
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
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30
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Handy RM, DesOrmeaux GJ, Barbeau PA, Frangos SM, Holloway GP. Independent, but not co-supplementation, with nitrate and resveratrol improves glucose tolerance and reduces markers of cellular stress in high-fat-fed male mice. Am J Physiol Regul Integr Comp Physiol 2023; 324:R317-R328. [PMID: 36622081 DOI: 10.1152/ajpregu.00196.2022] [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: 01/10/2023]
Abstract
Independent supplementation with nitrate (NIT) and resveratrol (RSV) enriches various aspects of mitochondrial biology in key metabolic tissues. Although RSV is known to activate Sirt1 and initiate mitochondrial biogenesis, the metabolic benefits elicited by dietary nitrate appear to be dependent on 5'-adenosine monophosphate-activated protein kinase (AMPK)-mediated signaling events, a process also linked to the activation of Sirt1. Although the benefits of individual supplementation with these compounds have been characterized, it is unknown if co-supplementation may produce superior metabolic adaptations. Thus, we aimed to determine if treatment with combined +NIT and +RSV (+RN) could additively alter metabolic adaptations in the presence of a high-fat diet (HFD). Both +RSV and +NIT improved glucose tolerance compared with HFD (P < 0.05); however, this response was attenuated following combined +RN supplementation. Within skeletal muscle, all supplements increased mitochondrial ADP sensitivity compared with HFD (P < 0.05), without altering mitochondrial content. Although +RSV and +NIT decreased hepatic lipid deposition compared with HFD (P < 0.05), this effect was abolished with +RN, which aligned with significant reductions in Sirt1 protein content (P < 0.05) after combined treatment, in the absence of changes to mitochondrial content or function. Within epididymal white adipose tissue (eWAT), all supplements reduced crown-like structure accumulation compared with HFD (P < 0.0001) and mitochondrial reactive oxygen species (ROS) emission (P < 0.05), alongside reduced adipocyte cross-sectional area (CSA) (P < 0.05), with the greatest effect observed after +RN treatment (P = 0.0001). Although the present data suggest additive changes in adipose tissue metabolism after +RN treatment, concomitant impairments in hepatic lipid homeostasis appear to prevent improvements in whole body glucose homeostasis observed with independent treatment, which may be Sirt1 dependent.
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Affiliation(s)
- Rachel M Handy
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
| | - Geneviève J DesOrmeaux
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
| | - Pierre-Andre Barbeau
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
| | - Sara M Frangos
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
| | - Graham P Holloway
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
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Wang Y, Zhao R, Wu C, Liang X, He L, Wang L, Wang X. Activation of the sirtuin silent information regulator 1 pathway inhibits pathological myocardial remodeling. Front Pharmacol 2023; 14:1111320. [PMID: 36843938 PMCID: PMC9950519 DOI: 10.3389/fphar.2023.1111320] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 01/30/2023] [Indexed: 02/12/2023] Open
Abstract
Myocardial remodeling refers to structural and functional disorders of the heart caused by molecular biological changes in the cardiac myocytes in response to neurological and humoral factors. A variety of heart diseases, such as hypertension, coronary artery disease, arrhythmia, and valvular heart disease, can cause myocardial remodeling and eventually lead to heart failure. Therefore, counteracting myocardial remodeling is essential for the prevention and treatment of heart failure. Sirt1 is a nicotinamide adenine dinucleotide+-dependent deacetylase that plays a wide range of roles in transcriptional regulation, energy metabolism regulation, cell survival, DNA repair, inflammation, and circadian regulation. It positively or negatively regulates myocardial remodeling by participating in oxidative stress, apoptosis, autophagy, inflammation, and other processes. Taking into account the close relationship between myocardial remodeling and heart failure and the involvement of SIRT1 in the development of the former, the role of SIRT1 in the prevention of heart failure via inhibition of myocardial remodeling has received considerable attention. Recently, multiple studies have been conducted to provide a better understanding of how SIRT1 regulates these phenomena. This review presents the progress of research involving SIRT1 pathway involvement in the pathophysiological mechanisms of myocardial remodeling and heart failure.
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Affiliation(s)
- Youheng Wang
- Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, Heart Center of Xinxiang Medical University, Xinxiang, China
| | - Rusheng Zhao
- Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, Heart Center of Xinxiang Medical University, Xinxiang, China
| | - Chengyan Wu
- Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, Heart Center of Xinxiang Medical University, Xinxiang, China
| | - Xuefei Liang
- Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, Heart Center of Xinxiang Medical University, Xinxiang, China
| | - Lei He
- Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, Heart Center of Xinxiang Medical University, Xinxiang, China,Department of Cardiology, Guangyuan Central Hospital, Guangyuan, China
| | - Libo Wang
- Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, Heart Center of Xinxiang Medical University, Xinxiang, China,College of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, China,*Correspondence: Libo Wang, ; Xuehui Wang,
| | - Xuehui Wang
- Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, Heart Center of Xinxiang Medical University, Xinxiang, China,*Correspondence: Libo Wang, ; Xuehui Wang,
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Tinosporaside from Tinospora cordifolia Encourages Skeletal Muscle Glucose Transport through Both PI-3-Kinase- and AMPK-Dependent Mechanisms. MOLECULES (BASEL, SWITZERLAND) 2023; 28:molecules28020483. [PMID: 36677541 PMCID: PMC9864719 DOI: 10.3390/molecules28020483] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 12/28/2022] [Accepted: 12/30/2022] [Indexed: 01/06/2023]
Abstract
The stem of Tinospora cordifolia has been traditionally used in traditional Indian systems of medicine for blood sugar control, without the knowledge of the underlying mechanism and chemical constitution responsible for the observed anti-diabetic effect. In the present study, Tinosporaside, a diterpenoid isolated from the stem of T. cordifolia, was investigated for its effects on glucose utilization in skeletal muscle cells, which was followed by determining the anti-hyperglycemic efficacy in our diabetic db/db mice model. We found that tinosporaside augmented glucose uptake by increasing the translocation of GLUT4 to the plasma membrane in L6 myotubes, upon prolonged exposure for 16 h. Moreover, tinosporaside treatment significantly increased the phosphorylation of protein kinase B/AKT (Ser-473) and 5' AMP-activated protein kinase (AMPK, Thr-172). These effects were abolished in the presence of the wortmannin and compound C. Administration of tinosporaside to db/db mice improved glucose tolerance and peripheral insulin sensitivity associated with increased gene expression and phosphorylation of the markers of phosphoinositide 3-kinases (PI3Ks) and AMPK signaling in skeletal muscle tissue. The findings revealed that tinosporaside exerted its antidiabetic efficacy by enhancing the rate of glucose utilization in skeletal muscle, mediated by PI3K- and AMPK-dependent signaling mechanisms.
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Harwansh RK, Yadav P, Deshmukh R. Current Insight into Novel Delivery Approaches of Resveratrol for Improving Therapeutic Efficacy and Bioavailability with its Clinical Updates. Curr Pharm Des 2023; 29:2921-2939. [PMID: 38053352 DOI: 10.2174/0113816128282713231129094715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 10/22/2023] [Accepted: 11/02/2023] [Indexed: 12/07/2023]
Abstract
Resveratrol (RSV) is a polyphenolic phytoalexin, and belongs to the stilbene family. RSV has several therapeutic activities such as cardioprotective, anticancer, and antioxidant. Apart from its therapeutic benefits, its pharmacological uses are limited due to low solubility, poor bioavailability, and short biological halflife. A researcher continuously focuses on overcoming the limitations of RSV through nanotechnology platforms to get the optimum health benefits. In this context, nanocarriers are pioneering to overcome these drawbacks. Nanocarriers possess high drug loading capacity, thermal stability, low production cost, longer shelflife, etc. Fortunately, scientists were proficient in delivering resveratrol-based nanocarriers in the present scenario. Nanocarriers can deliver drugs to the target sites without compromising the bioavailability. Thus, this review highlights how the latest nanocarrier systems overcome the shortcomings of RSV, which will be good for improving therapeutic efficacy and bioavailability. Moreover, recent updates on resveratrol-based novel formulations and their clinical trials have been addressed to manage several health-related problems.
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Affiliation(s)
- Ranjit K Harwansh
- Institute of Pharmaceutical Research, GLA University, Mathura 281406, India
| | - Paras Yadav
- Institute of Pharmaceutical Research, GLA University, Mathura 281406, India
| | - Rohitas Deshmukh
- Institute of Pharmaceutical Research, GLA University, Mathura 281406, India
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Vo KCT, Sato Y, Kawamura K. Improvement of oocyte quality through the SIRT signaling pathway. Reprod Med Biol 2023; 22:e12510. [PMID: 36845003 PMCID: PMC9949364 DOI: 10.1002/rmb2.12510] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 01/23/2023] [Accepted: 02/05/2023] [Indexed: 02/25/2023] Open
Abstract
Background Oocyte quality is one of the major deciding factors in female fertility competence. Methods PubMed database was searched for reviews by using the following keyword "oocyte quality" AND "Sirtuins". The methodological quality of each literature review was assessed using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement. Main Findings Oxidative stress has been recognized as the mechanism attenuating oocyte quality. Increasing evidence from animal experiments and clinical studies has confirmed the protective roles of the sirtuin family in improving oocyte quality via an antioxidant effect. Conclusion The protective roles in the oocyte quality of the sirtuin family have been increasingly recognized.
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Affiliation(s)
- Kim Cat Tuyen Vo
- Graduate School of MedicineInternational University of Health and Welfare School of MedicineNarita‐shiJapan
- Department of Obstetrics & GynaecologyUniversity of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh CityVietnam
| | - Yorino Sato
- Graduate School of MedicineInternational University of Health and Welfare School of MedicineNarita‐shiJapan
- Department of Obstetrics and GynecologyJuntendo University Faculty of MedicineBunkyokuJapan
| | - Kazuhiro Kawamura
- Graduate School of MedicineInternational University of Health and Welfare School of MedicineNarita‐shiJapan
- Department of Obstetrics and GynecologyJuntendo University Faculty of MedicineBunkyokuJapan
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Bertoncini-Silva C, Zingg JM, Fassini PG, Suen VMM. Bioactive dietary components-Anti-obesity effects related to energy metabolism and inflammation. Biofactors 2022; 49:297-321. [PMID: 36468445 DOI: 10.1002/biof.1921] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 11/18/2022] [Indexed: 12/10/2022]
Abstract
Obesity is the result of the long-term energy imbalance between the excess calories consumed and the few calories expended. Reducing the intake of energy dense foods (fats, sugars), and strategies such as fasting and caloric restriction can promote body weight loss. Not only energy in terms of calories, but also the specific composition of the diet can affect the way the food is absorbed and how its energy is stored, used or dissipated. Recent research has shown that bioactive components of food, such as polyphenols and vitamins, can influence obesity and its pathologic complications such as insulin resistance, inflammation and metabolic syndrome. Individual micronutrients can influence lipid turnover but for long-term effects on weight stability, dietary patterns containing several micronutrients may be required. At the molecular level, these molecules modulate signaling and the expression of genes that are involved in the regulation of energy intake, lipid metabolism, adipogenesis into white, beige and brown adipose tissue, thermogenesis, lipotoxicity, adipo/cytokine synthesis, and inflammation. Higher concentrations of these molecules can be reached in the intestine, where they can modulate the composition and action of the microbiome. In this review, the molecular mechanisms by which bioactive compounds and vitamins modulate energy metabolism, inflammation and obesity are discussed.
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Affiliation(s)
- Caroline Bertoncini-Silva
- Department of Internal Medicine, Division of Nutrology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | - Jean-Marc Zingg
- Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, Florida, USA
| | - Priscila Giacomo Fassini
- Department of Internal Medicine, Division of Nutrology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | - Vivian Marques Miguel Suen
- Department of Internal Medicine, Division of Nutrology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
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Nasrollahi Z, ShahaniPour K, Monajemi R, Ahadi AM. Effect of quercetin and Abelmoschus esculentus (L.) Moench on lipids metabolism and blood glucose through AMPK-α in diabetic rats (HFD/STZ). J Food Biochem 2022; 46:e14506. [PMID: 36369969 DOI: 10.1111/jfbc.14506] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 10/06/2022] [Accepted: 10/21/2022] [Indexed: 11/15/2022]
Abstract
Phosphoenolpyruvate carboxykinase (PEPCK) is a key enzyme in the glyconeogenesis pathway. The AMP-activated protein kinase alpha (AMPK-α) pathway regulates PEPCK, which itself is activated by the AMP/ATP ratio and liver kinase B1 (KB1). The Abelmoschus esculentus (L.) Moench (okra) plant contains a large amount of quercetin that can function as an agonist or an antagonist. The aim of this study was to examine the effects of quercetin flavonoid and A. esculentus extract on the level of AMPK-α expression and associated metabolic pathways. The findings demonstrate that metformin, quercetin, and okra extract may significantly raise AMPK-α levels while significantly lowering PEPCK and hormone-sensitive lipase (HSL) levels, in addition to improving glucose and lipid profiles. By stimulating KB1, these substances increased AMPK-α activation. Additionally, AMPK-α activation improved insulin resistance and Glucose transporter type 4 (GLUT4) gene expression levels. Since AMPK-α maintains energy balance and its activity has not been reported to be inhibited so far, it could be a potent therapeutic target. PRACTICAL APPLICATIONS: The development of effective AMPK-α agonists and antagonists holds promise for the treatment of metabolic disorders like diabetes. Dietary polyphenols are a valuable source for developing new drugs. However, due to the lack of understanding of the underlying mechanisms of their effect on cells, their use in the treatment of diabetes is controversial. In addition to chemicals that have medicinal benefits, chemists are searching for less harmful substances. Using plants containing bioactive chemicals for this purpose can be a good alternative to chemical drugs.
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Affiliation(s)
- Zohreh Nasrollahi
- Department of Biochemistry, Falavarjan Branch, Islamic Azad University, Isfahan, Iran
| | - Kahin ShahaniPour
- Department of Biochemistry, Falavarjan Branch, Islamic Azad University, Isfahan, Iran
| | - Ramesh Monajemi
- Department of Biology, Falavarjan Branch, Islamic Azad University, Isfahan, Iran
| | - Ali Mohammad Ahadi
- Department of Genetics, Faculty of Science, Shahrekord University, Shahrekord, Iran
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Liu J, Liu J, Zeng D, Wang H, Wang Y, Xiong J, Chen X, Luo J, Chen T, Xi Q, Jiang Q, Zhang Y. miR-143-null Is against Diet-Induced Obesity by Promoting BAT Thermogenesis and Inhibiting WAT Adipogenesis. Int J Mol Sci 2022; 23:13058. [PMID: 36361843 PMCID: PMC9658130 DOI: 10.3390/ijms232113058] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 10/14/2022] [Accepted: 10/25/2022] [Indexed: 09/29/2023] Open
Abstract
Excessive energy intake is the main cause of obesity, and stimulation of brown adipose tissue (BAT) thermogenesis has emerged as an attractive tool for anti-obesity. Although miR-143 has been reported to promote white adipocyte differentiation, its role in BAT remains unclear. In our study, we found that during HFD-induced obesity, the expression of miR-143 in BAT was significantly reduced, and the expression of miR-143 in WAT first increased and then decreased. Knockout (KO) of miR-143 with CRISPR/Cas9 did not affect the energy metabolism of normal diet fed mice and brown adipocyte differentiation but inhibited the differentiation of white adipocytes. Importantly, during high fat diet-induced obesity, miR-143KO significantly reduced body weight, and improved energy expenditure, insulin sensitivity, and glucose tolerance. Further exploration showed that miR-143KO reduced the weight of adipose tissue, promoted mitochondrial number and functions, induced thermogenesis and lipolysis of BAT, increased lipolysis, and inhibited lipogenesis of white adipose tissue (WAT). Our study considerably improves our collective understanding of the function of miR-143 in adipose tissue and its potential significance in anti-obesity and provides a new avenue for the management of obesity through the inhibition of miR-143 in BAT and WAT.
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Affiliation(s)
- Jie Liu
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Jiatao Liu
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Dewei Zeng
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Huan Wang
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Yun Wang
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Jiali Xiong
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Xingping Chen
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
- Jiangxi Province Key Laboratory of Animal Nutrition, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China
| | - Junyi Luo
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Ting Chen
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Qianyun Xi
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Qingyan Jiang
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Yongliang Zhang
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
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Zin CAJCM, Mohamed WMIW, Khan NAK, Ishak WRW. Effects of Fruit and Vegetable Polyphenols on the Glycemic Control and Metabolic Parameters in Type 2 Diabetes Mellitus: A Review. Prev Nutr Food Sci 2022; 27:257-264. [PMID: 36313061 PMCID: PMC9585403 DOI: 10.3746/pnf.2022.27.3.257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
The high prevalence of diabetes in recent decades has been associated with lifestyle changes and dietary habits correlated with economic development. Fruits and vegetables are a vital source of nutraceuticals and components of the healthy diet recommended in the medical nutrition therapy for type 2 diabetes mellitus (T2DM) to prevent hyperglycemia and related complications. They are low in calories and rich in dietary fiber, consist of many polyphenols, and are an essential component of a healthy lifestyle. Recently, researchers have developed a significant interest in understanding the effects of polyphenols (flavonoids and non-flavonoids) on blood glucose levels. In this review, the authors summarize the effects of polyphenols commonly found in the fruits and vegetables, such as resveratrol and anthocyanins, on the glycemic control and metabolic parameters, based on human clinical trials. Significant reductions in fasting blood glucose, glycated hemoglobin, and low-density lipoprotein cholesterol levels were reported after resveratrol, anthocyanin, and naringin were administered to patients with prediabetes and diabetes. Decreased insulin levels were observed after resveratrol intervention but not with the other types of polyphenols. These effects of polyphenolic compounds on the glycemic and metabolic parameters might be mediated by multiple pathophysiological mechanisms, such as activating regulator proteins to increase insulin signaling and eventually suppress insulin resistance. The benefits of certain polyphenols on T2DM remain ambiguous; therefore, further studies, especially clinical trials, are required to substantiate the available evidence.
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Affiliation(s)
| | - Wan Mohd Izani Wan Mohamed
- Department of Internal Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
| | | | - Wan Rosli Wan Ishak
- Nutrition Program, School of Health Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia,
Correspondence to Wan Rosli Wan Ishak, E-mail:
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Abo Alrob O, Al-Horani RA, Altaany Z, Nusair MB. Synergistic Beneficial Effects of Resveratrol and Diet on High-Fat Diet-Induced Obesity. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58091301. [PMID: 36143977 PMCID: PMC9503422 DOI: 10.3390/medicina58091301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/13/2022] [Accepted: 09/15/2022] [Indexed: 11/16/2022]
Abstract
Introduction: Despite decades of research, obesity and its related medical complications remain a major health concern globally. Therefore, novel therapeutic strategies are needed to combat obesity and its numerous debilitating complications. Resveratrol (RES) has a potential therapeutic effect in obesity and diabetes by improving oxidative metabolism and insulin signaling. Background and Objectives: The aim of this study was to investigate the effect of RES treatment on weight loss and glucose and fatty acid metabolism. Methods: Obesity was induced in 24 mice by exposure to a high-fat diet (HFD) for 8 weeks. Mice were randomly assigned to one group of either: group 1: control, non-treated low-fat diet (LFD) for 12 weeks (n = 8), group 2: non-treated high-fat diet (HFD) for 12 weeks (n = 8), group 3: RES-treated HFD (HFD + RES) (n = 8), or group 4: RES-treated and switched to LFD (HFD-LFD + RES) (n = 8). HFD + RES mice were first fed an HFD for 8 weeks followed by 4 weeks of RES. The HFD-LFD + RES group was first fed an HFD for 8 weeks and then treated with RES and switched to an LFD for 4 weeks. Results: After 12 weeks, group 2 mice had significantly higher body weights compared to group 1 (23.71 ± 1.95 vs. 47.83 ± 2.27; p < 0.05). Group 4 had a significant decrease in body weight and improvement in glucose tolerance compared to mice in group 2 (71.3 ± 1.17 vs. 46.1 ± 1.82 and 40.9 ± 1.75, respectively; p < 0.05). Skeletal muscles expression of SIRT1, SIRT3, and PGC1α were induced in group 3 and 4 mice compared to group 2 (p < 0.01), with no changes in AMP-activated protein kinase expression levels. Furthermore, combination of RES and diet ameliorated skeletal muscle intermediate lipid accumulation and significantly improved insulin sensitivity and secretion. Conclusions: The results of this study suggest a synergistic beneficial effect of LFD and RES to lower body weight and enhance glucose and fatty acid metabolism.
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Affiliation(s)
- Osama Abo Alrob
- Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Yarmouk University, Irbid 211-63, Jordan or
- Correspondence:
| | - Ramzi A. Al-Horani
- Department of Exercise Science, Yarmouk University, Irbid 211-63, Jordan
| | - Zaid Altaany
- Department of Basic Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan
| | - Mohammad B. Nusair
- Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Yarmouk University, Irbid 211-63, Jordan or
- Department of Sociobehavioral and Administrative Pharmacy, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33314, USA
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The Role and Regulatory Mechanism of Brown Adipose Tissue Activation in Diet-Induced Thermogenesis in Health and Diseases. Int J Mol Sci 2022; 23:ijms23169448. [PMID: 36012714 PMCID: PMC9408971 DOI: 10.3390/ijms23169448] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 08/15/2022] [Accepted: 08/18/2022] [Indexed: 11/23/2022] Open
Abstract
Brown adipose tissue (BAT) has been considered a vital organ in response to non-shivering adaptive thermogenesis, which could be activated during cold exposure through the sympathetic nervous system (SNS) or under postprandial conditions contributing to diet-induced thermogenesis (DIT). Humans prefer to live within their thermal comfort or neutral zone with minimal energy expenditure created by wearing clothing, making shelters, or using an air conditioner to regulate their ambient temperature; thereby, DIT would become an important mechanism to counter-regulate energy intake and lipid accumulation. In addition, there has been a long interest in the intriguing possibility that a defect in DIT predisposes one to obesity and other metabolic diseases. Due to the recent advances in methodology to evaluate the functional activity of BAT and DIT, this updated review will focus on the role and regulatory mechanism of BAT biology in DIT in health and diseases and whether these mechanisms are applicable to humans.
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Resolvin D3 improves the impairment of insulin signaling in skeletal muscle and nonalcoholic fatty liver disease through AMPK/autophagy-associated attenuation of ER stress. Biochem Pharmacol 2022; 203:115203. [DOI: 10.1016/j.bcp.2022.115203] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 07/30/2022] [Accepted: 08/02/2022] [Indexed: 11/17/2022]
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Luo J, Chen S, Wang L, Zhao X, Piao C. Pharmacological effects of polydatin in the treatment of metabolic diseases: A review. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 102:154161. [PMID: 35636169 DOI: 10.1016/j.phymed.2022.154161] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 04/14/2022] [Accepted: 05/07/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Metabolic diseases (MDs), a series of chronic disorders, severely decreases the quality of life for patients but also cause a heavy economic burden. Emerging evidence suggests that Polydatin (PD), an important glucoside of resveratrol, is widely distributed in many plants and has shown good therapeutic potential in metabolic diseases. PURPOSE To review the PD discovered before 2021 and their potential to treat metabolic diseases. The activities against diabetes, Obesity, atherosclerosis, NAFLD, NASH, hyperlipidemia, and gout with special emphasis on pharmacology, pharmacokinetics, mechanisms of action, possible roles in current medicine, and future perspectives are discussed. METHODS A comprehensive search of published literature was conducted to locate original publications pertaining to polydatin and MDs through the end of 2021 using MEDLINE, Elsevier, Springer, PubMed, Scholar, and CNKI databases. The main inquiry used was for the presence of the following keywords in various combinations in the abstracts: 'Polydatin', 'Metabolic diseases', 'Pharmacology', 'Toxicology', 'Pharmacokinetics', 'Diabetes', 'Obesity', 'Atherosclerosis', 'Non-alcoholic fatty liver disease', 'Non-alcoholic steatohepatitis', 'Hyperlipidemia', and 'Gout'. RESULTS The search yielded 987 articles, of which 33 articles were included in this review. Studies have revealed that PD can promote insulin secretion, alleviate insulin resistance, regulate glucose and lipid metabolism, reduce liver lipid deposition, inhibit inflammation, oxidative stress, and decrease uric acid deposition in preclinical experiments. The underlying mechanisms of PD in treatment MDs may be attributed to the regulation of multiple signaling pathways, including. NF-κB, AGEs/RAGE, MAPK/ERK, AMPK/LDLR, IRS1/PI3K/AKT, LKB1/AMPK, PPARβ-NO, SIRT1-PGC-1α-SOD2, PKC, etc., The pharmacokinetic profiles of PD provide valuable information on therapeutic efficacy in treating metabolic diseases. CONCLUSION This review summarizes the available reports and evidence which support the use of PD as a potential candidate in the treatment of MDs and provides an overview of the modulatory effects of PD in metabolic diseases and cell signaling pathways, which may have important implications in its future clinical use.
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Affiliation(s)
- Jinli Luo
- Institution of Shenzhen Hospital, Guangzhou University of Chinese Medicine (Futian), Shenzhen, 518000, China
| | - Shuo Chen
- Institution of Shenzhen Hospital, Guangzhou University of Chinese Medicine (Futian), Shenzhen, 518000, China
| | - Li Wang
- Institution of Shenzhen Hospital, Guangzhou University of Chinese Medicine (Futian), Shenzhen, 518000, China
| | - Xiaohua Zhao
- Institution of Shenzhen Hospital, Guangzhou University of Chinese Medicine (Futian), Shenzhen, 518000, China
| | - Chunli Piao
- Institution of Shenzhen Hospital, Guangzhou University of Chinese Medicine (Futian), Shenzhen, 518000, China.
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Zhao G, Yang L, Zhong W, Hu Y, Tan Y, Ren Z, Ban Q, Yang CS, Wang Y, Wang Z. Polydatin, A Glycoside of Resveratrol, Is Better Than Resveratrol in Alleviating Non-alcoholic Fatty Liver Disease in Mice Fed a High-Fructose Diet. Front Nutr 2022; 9:857879. [PMID: 35651514 PMCID: PMC9149290 DOI: 10.3389/fnut.2022.857879] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 03/04/2022] [Indexed: 12/14/2022] Open
Abstract
Resveratrol (RES) is considered to be an activator of AMP-activated protein kinase (AMPK) with many reported health benefits. Polydatin (POD) is a natural precursor and glycosylated form of RES. The glycoside structure of POD alters the bioactivity. Overnutrition-stimulated reactive oxygen species (ROS) promote the AMPK suppression and metabolic dysregulation. The present work compared the effects of POD and RES in ameliorating energy homeostasis imbalance in mice fed a high-fructose diet and elucidated the underlying mechanisms of action. Our results showed that POD elevated the fecal levels of valeric acid and caproic acid via modification of gut microbiota, while RES did not significantly influence the levels of fecal short-chain fatty acids (SCFAs). Both POD and RES markedly decreased the oxidative stress and activated the AMPK signaling pathways in the liver. POD and RES exerted a similar effect in alleviating glucose dysmetabolism, but POD was more effective in ameliorating lipid dysmetabolism than RES. Furthermore, valeric acid and caproic acid alone can activate the AMPK and ameliorate hypercholesterolemia, and enhance the effects of POD on improving lipid metabolism in mice. Overall, for the first time, we demonstrated that POD administration elevated the fecal levels of valeric acid and caproic acid by modifying gut microbiota, thus promoting AMPK activation may be the underlying mechanism that POD is superior to RES in alleviating the lipid dysmetabolism. Our results suggest that POD may be an alternative for RES as an AMPK activator.
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Affiliation(s)
- Guangshan Zhao
- Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China.,Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, China.,School of Food Science and Technology, Henan Agricultural University, Zhengzhou, China.,Guangdong Province Key Laboratory of Bioengineering Medicine, Guangzhou, China.,Guangdong Provincial Biotechnology Drug and Engineering Technology Research Center, Guangzhou, China.,Guangzhou Jinan Biomedicine Research and Development Center Co., Ltd., Guangzhou, China
| | - Lian Yang
- Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China
| | - Wenshen Zhong
- Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China
| | - Yuze Hu
- Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Yu Tan
- Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Zhe Ren
- Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, China.,Guangdong Provincial Biotechnology Drug and Engineering Technology Research Center, Guangzhou, China.,Guangzhou Jinan Biomedicine Research and Development Center Co., Ltd., Guangzhou, China
| | - Qiuyan Ban
- College of Horticulture, Henan Agricultural University, Zhengzhou, China
| | - Chung S Yang
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, United States
| | - Yifei Wang
- Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, China.,Guangdong Provincial Biotechnology Drug and Engineering Technology Research Center, Guangzhou, China.,Guangzhou Jinan Biomedicine Research and Development Center Co., Ltd., Guangzhou, China
| | - Zhiping Wang
- Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China
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Faal M, Manouchehri H, Changizi R, Bootorabi F, Khorramizadeh MR. Assessment of resveratrol on diabetes of zebrafish ( Danio rerio). J Diabetes Metab Disord 2022; 21:823-833. [PMID: 35673499 PMCID: PMC9167402 DOI: 10.1007/s40200-021-00964-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 12/23/2021] [Indexed: 01/29/2023]
Abstract
Purpose Zebrafish (Danio rerio) is an established model for studying various metabolic diseases. The aim of this study was to evaluate the effect of resveratrol as a natural polyphenol on reducing inflammation caused by hyperglycemia (diabetes) and its effect on digestive tissue as well as TNF-α, IFN-γ, and INL1β genes in zebrafish. Methods Within a 20-day period, the research was performed on 120 adult zebrafish, which were randomly classified into eight groups: two experimental treatments (induced glucose = +G) and (without glucose = -G), where each main group was as follows: CTRL = control and RSV resveratrol with doses 10, 20, and 30 μmol/L. At the end of the period, the blood glucose level was measured using glucose test strip, staining of intestinal tissue was done by hematoxylin and eosin (H&E), and expression of INF-γ, IL1-β, and TNF-α genes extracted from the intestinal was measured via internal method RT-PCR. Data analysis in this study was performed using SPSS software version 21. One-way ANOVA and mean comparison of treatments by Duncan test were used for data analysis. All statistical analyses were performed at a significant level (P < 0.5) where the mean data were presented with standard deviation. Results According to the results, the lowest blood sugar level at the end of the experiment belonged to the group (G-RSV20) where no significant difference was observed between treatments (P > 0.05). The highest expression of IL1-β gene belonged to the (G + CTRL) group (P < 0.05), while the (G + RSV20) group showed the lowest expression of the INF-γ gene and had a significant difference with other groups (P < 0.05). In (G + RSV10) treatment, the lowest expression of TNF-α gene was observed and there was no significant difference with other treatments (P > 0.05). Resveratrol would improve the absorption of nutrients in the intestinal tissue by increasing the number of goblet cells as well as the width and height of the villi. Conclusion Collectively, this study indicated that treatment with resveratrol could improve metabolic-mediated performances by reducing blood glucose, increasing food absorption in the intestine tissue, and reducing the expression of inflammatory genes in type 2 diabetic zebrafish model.
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Affiliation(s)
- Mina Faal
- Department of Aquaculture Science, Babol Branch, Islamic Azad University, Babol, Iran
| | - Hamed Manouchehri
- Department of Aquaculture Science, Babol Branch, Islamic Azad University, Babol, Iran
| | - Reza Changizi
- Department of Aquaculture Science, Babol Branch, Islamic Azad University, Babol, Iran
| | - Fatemeh Bootorabi
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Mohammad Reza Khorramizadeh
- Biosensor Research Center, Endocrinology Metabolism Molecular-Cellular Sciences Institute, Zebra fish core Facility (ZFIN ID: ZDB-LAB-1901172), Endocrinology and Metabolism research Institute, Tehran university of Medical Sciences, Tehran, Iran
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Saurin S, Meineck M, Erkel G, Opatz T, Weinmann-Menke J, Pautz A. Drug Candidates for Autoimmune Diseases. Pharmaceuticals (Basel) 2022; 15:503. [PMID: 35631330 PMCID: PMC9143092 DOI: 10.3390/ph15050503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Revised: 04/12/2022] [Accepted: 04/14/2022] [Indexed: 12/10/2022] Open
Abstract
Most of the immunosuppressive drugs used in the clinic to prevent organ rejection or to treat autoimmune disorders were originally isolated from fungi or bacteria. Therefore, in addition to plants, these are valuable sources for identification of new potent drugs. Many side effects of established drugs limit their usage and make the identification of new immunosuppressants necessary. In this review, we present a comprehensive overview of natural products with potent anti-inflammatory activities that have been tested successfully in different models of chronic inflammatory autoimmune diseases. Some of these candidates already have passed first clinical trials. The anti-inflammatory potency of these natural products was often comparable to those of established drugs, and they could be used at least in addition to standard therapy to reduce their dose to minimize unwanted side effects. A frequent mode of action is the inhibition of classical inflammatory signaling pathways, such as NF-κB, in combination with downregulation of oxidative stress. A drawback for the therapeutic use of those natural products is their moderate bioavailability, which can be optimized by chemical modifications and, in addition, further safety studies are necessary. Altogether, very interesting candidate compounds exist which have the potential to serve as starting points for the development of new immunosuppressive drugs.
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Affiliation(s)
- Sabrina Saurin
- 1st Department of Medicine, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany; (S.S.); (M.M.)
- Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany
| | - Myriam Meineck
- 1st Department of Medicine, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany; (S.S.); (M.M.)
- Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany
| | - Gerhard Erkel
- Department of Molecular Biotechnology and Systems Biology, Technical University, 67663 Kaiserslautern, Germany;
| | - Till Opatz
- Department of Chemistry, Johannes Gutenberg University, 55099 Mainz, Germany;
| | - Julia Weinmann-Menke
- 1st Department of Medicine, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany; (S.S.); (M.M.)
- Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany
| | - Andrea Pautz
- Department of Pharmacology, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany
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Um JH, Park SY, Hur JH, Lee HY, Jeong KH, Cho Y, Lee SH, Yoon SM, Choe S, Choi CS. Bone morphogenic protein 9 is a novel thermogenic hepatokine secreted in response to cold exposure. Metabolism 2022; 129:155139. [PMID: 35063533 DOI: 10.1016/j.metabol.2022.155139] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 01/03/2022] [Accepted: 01/13/2022] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Maintaining a constant core body temperature is essential to homeothermic vertebrate survival. Adaptive thermogenesis in brown adipose tissue and skeletal muscle is the primary mechanism of adjustment to an external stimulus such as cold exposure. Recently, several reports have revealed that the liver can play a role as a metabolic hub during adaptive thermogenesis. In this study, we suggest that the liver plays a novel role in secreting thermogenic factors in adaptive thermogenesis. Bone morphogenetic protein 9 (BMP9) is a hepatokine that regulates many biological processes, including osteogenesis, chondrogenesis, hematopoiesis, and angiogenesis. Previously, BMP9 was suggested to affect preadipocyte proliferation and differentiation. However, the conditions and mechanisms underlying hepatic expression and secretion and adipose tissue browning of BMP9 remain largely unknown. In this study, we investigated the physiological conditions for secretion and the regulatory mechanism of hepatic Bmp9 expression and the molecular mechanism by which BMP9 induces thermogenic gene program activation in adipose tissue. Here, we also present the pharmacological effects of BMP9 on a high-fat-induced obese mouse model. METHODS To investigate the adaptive thermogenic role of BMP9 in vivo, we challenged mice with cold temperature exposure for 3 weeks and then examined the BMP9 plasma concentration and hepatic expression level. The cellular mechanism of hepatic Bmp9 expression under cold exposure was explored through promoter analysis. To identify the role of BMP9 in the differentiation of brown and beige adipocytes, we treated pluripotent stem cells and inguinal white adipose tissue (iWAT)-derived stromal-vascular (SV) cells with BMP9, and brown adipogenesis was monitored by examining thermogenic gene expression and signaling pathways. Furthermore, to evaluate the effect of BMP9 on diet-induced obesity, changes in body composition and glucose tolerance were analyzed in mice administered recombinant BMP9 (rBMP9) for 8 weeks. RESULTS Hepatic Bmp9 expression and plasma levels in mice were significantly increased after 3 weeks of cold exposure. Bmp9 mRNA expression in the liver was regulated by transcriptional activation induced by cAMP response-element binding protein (CREB) and CREB-binding protein (CBP) on the Bmp9 promoter. Treatment with BMP9 promoted the differentiation of multipotent stem cells and iWAT-derived SV cells into beige adipocytes, as indicated by the increased expression of brown adipocyte and mitochondrial biogenesis markers. Notably, activation of the mothers against decapentaplegic homolog 1 (Smad1) and p44/p42 mitogen-activated protein kinase (MAPK) pathways was required for the induction of uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC1α) expression in BMP9-induced differentiation of SVs into beige adipocytes. The administration of rBMP9 in vivo also induced browning markers in white adipose tissue. In high-fat diet-induced obese mice, rBMP9 administration conferred protection against obesity and enhanced glucose tolerance. CONCLUSIONS BMP9 is a hepatokine regulated by cold-activated CREB and CBP and enhances glucose and fat metabolism by promoting the activation of the thermogenic gene program in adipocytes. These data implicate BMP9 as a potential pharmacological tool for protecting against obesity and type 2 diabetes.
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Affiliation(s)
- Jee-Hyun Um
- Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea
| | - Shi-Young Park
- Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea
| | - Jang Ho Hur
- Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea
| | - Hui-Young Lee
- Division of Molecular Medicine, Department of Medicine, Gachon University College of Medicine, Incheon 21565, Republic of Korea
| | - Kyeong-Hoon Jeong
- Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea
| | - Yoonil Cho
- Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea; Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Republic of Korea
| | - Shin-Hae Lee
- Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea
| | - So-Mi Yoon
- Laboratory of Drugs to Medicine, Joint Center for Biosciences, Incheon 21999, Republic of Korea
| | - Senyon Choe
- Laboratory of Drugs to Medicine, Joint Center for Biosciences, Incheon 21999, Republic of Korea
| | - Cheol Soo Choi
- Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea; Division of Molecular Medicine, Department of Medicine, Gachon University College of Medicine, Incheon 21565, Republic of Korea; Endocrinology, Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea.
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Bukhari SNA. Dietary Polyphenols as Therapeutic Intervention for Alzheimer’s Disease: A Mechanistic Insight. Antioxidants (Basel) 2022; 11:antiox11030554. [PMID: 35326204 PMCID: PMC8945272 DOI: 10.3390/antiox11030554] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 03/14/2022] [Accepted: 03/14/2022] [Indexed: 02/06/2023] Open
Abstract
Dietary polyphenols encompass a diverse range of secondary metabolites found in nature, such as fruits, vegetables, herbal teas, wine, and cocoa products, etc. Structurally, they are either derivatives or isomers of phenol acid, isoflavonoids and possess hidden health promoting characteristics, such as antioxidative, anti-aging, anti-cancerous and many more. The use of such polyphenols in combating the neuropathological war raging in this generation is currently a hotly debated topic. Lately, Alzheimer’s disease (AD) is emerging as the most common neuropathological disease, destroying the livelihoods of millions in one way or another. Any therapeutic intervention to curtail its advancement in the generation to come has been in vain to date. Using dietary polyphenols to construct the barricade around it is going to be an effective strategy, taking into account their hidden potential to counter multifactorial events taking place under such pathology. Besides their strong antioxidant properties, naturally occurring polyphenols are reported to have neuroprotective effects by modulating the Aβ biogenesis pathway in Alzheimer’s disease. Thus, in this review, I am focusing on unlocking the hidden secrets of dietary polyphenols and their mechanistic advantages to fight the war with AD and related pathology.
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Affiliation(s)
- Syed Nasir Abbas Bukhari
- Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Aljouf 2014, Saudi Arabia
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Oh H, Cho W, Abd El-Aty AM, Jeong JH, Jung TW. Resolvin D3 Improves the Impairment of Insulin Signaling in Skeletal Muscle and Nonalcoholic Fatty Liver Disease Through AMPK/Autophagy-Associated Attenuation of ER Stress. SSRN ELECTRONIC JOURNAL 2022. [DOI: 10.2139/ssrn.4149178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
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Nie T, Cooper GJS. Mechanisms Underlying the Antidiabetic Activities of Polyphenolic Compounds: A Review. Front Pharmacol 2021; 12:798329. [PMID: 34970150 PMCID: PMC8712966 DOI: 10.3389/fphar.2021.798329] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 11/18/2021] [Indexed: 12/16/2022] Open
Abstract
Polyphenolic compounds are thought to show considerable promise for the treatment of various metabolic disorders, including type 2 diabetes mellitus (T2DM). This review addresses evidence from in vitro, in vivo, and clinical studies for the antidiabetic effects of certain polyphenolic compounds. We focus on the role of cytotoxic human amylin (hA) aggregates in the pathogenesis of T2DM, and how polyphenols can ameliorate this process by suppressing or modifying their formation. Small, soluble amylin oligomers elicit cytotoxicity in pancreatic islet β-cells and may thus cause β-cell disruption in T2DM. Amylin oligomers may also contribute to oxidative stress and inflammation that lead to the triggering of β-cell apoptosis. Polyphenols may exert antidiabetic effects via their ability to inhibit hA aggregation, and to modulate oxidative stress, inflammation, and other pathways that are β-cell-protective or insulin-sensitizing. There is evidence that their ability to inhibit and destabilize self-assembly by hA requires aromatic molecular structures that bind to misfolding monomers or oligomers, coupled with adjacent hydroxyl groups present on single phenyl rings. Thus, these multifunctional compounds have the potential to be effective against the pleiotropic mechanisms of T2DM. However, substantial further research will be required before it can be determined whether a polyphenol-based molecular entity can be used as a therapeutic for type 2 diabetes.
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Affiliation(s)
- Tina Nie
- School of Biological Sciences, Faculty of Science, the University of Auckland, Auckland, New Zealand
| | - Garth J. S. Cooper
- School of Biological Sciences, Faculty of Science, the University of Auckland, Auckland, New Zealand
- The Maurice Wilkins Centre for Molecular Biodiscovery, Faculty of Science, the University of Auckland, Auckland, New Zealand
- Centre for Advanced Discovery and Experimental Therapeutics, Division of Cardiovascular Sciences, Faculty of Biology Medicine & Health, School of Medical Sciences, The University of Manchester, Manchester, United Kingdom
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Díaz-Orozco LE, Méndez-Sánchez N. Nutraceuticals and microbiota. Minerva Gastroenterol (Torino) 2021; 67:326-338. [PMID: 33978392 DOI: 10.23736/s2724-5985.21.02914-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Nutraceuticals are defined as products isolated or purified from foods that are generally sold in medicinal or dosage forms not usually associated with food which is demonstrated to have a physiological benefit or provide protection against chronic disease. In this context, the products offered should be rigorously evaluated by international regulatory agencies. More recently, nutraceuticals have been proposed as a potential preventive and therapeutic option in the assessment of chronic diseases, mainly by altering the microbiome composition. However, the current lack of conclusive evidence supporting the "healthy" or "normal" microbiome, along with the dysbiosis concept paradigm, could be both contributing to the lack of homogeneous results. These issues may be solved in the next years with the use of emergent technologies in the individual's microbiome assessment and its fluctuations in time or related to many factors, such as nutraceuticals. Additionally, future research assessing the independent association between the dysbiosis modification and any "potential" nutraceutical product (including bioactive ingredient or chemical compound in food) is going to enlarge the currently reduced "established nutraceuticals" group. In this work we have assessed the nutraceutical's potential role as a microbiome-targeted manipulation therapy, and the gut-liver axis involved in the digestive diseases' pathogenesis and progression, including the chronic liver diseases. Moreover, microbiome targeted nutraceuticals that show consistent results might be further included in clinical research and trials in the therapeutic assessment of chronic diseases. Finally, the indication of these quality microbiome-targeted nutraceuticals will undoubtedly carry health benefits for individuals.
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Affiliation(s)
- Luis E Díaz-Orozco
- National Autonomous University of Mexico, Mexico City, Mexico
- Unit of Liver Research, Medica Sur Clinic and Foundation, Mexico City, Mexico
| | - Nahum Méndez-Sánchez
- National Autonomous University of Mexico, Mexico City, Mexico -
- Unit of Liver Research, Medica Sur Clinic and Foundation, Mexico City, Mexico
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