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Chevalley T, Dübi M, Fumeaux L, Merli MS, Sarre A, Schaer N, Simeoni U, Yzydorczyk C. Sexual Dimorphism in Cardiometabolic Diseases: From Development to Senescence and Therapeutic Approaches. Cells 2025; 14:467. [PMID: 40136716 PMCID: PMC11941476 DOI: 10.3390/cells14060467] [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: 02/12/2025] [Revised: 03/03/2025] [Accepted: 03/14/2025] [Indexed: 03/27/2025] Open
Abstract
The global incidence and prevalence of cardiometabolic disorders have risen significantly in recent years. Although lifestyle choices in adulthood play a crucial role in the development of these conditions, it is well established that events occurring early in life can have an important effect. Recent research on cardiometabolic diseases has highlighted the influence of sexual dimorphism on risk factors, underlying mechanisms, and response to therapies. In this narrative review, we summarize the current understanding of sexual dimorphism in cardiovascular and metabolic diseases in the general population and within the framework of the Developmental Origins of Health and Disease (DOHaD) concept. We explore key risk factors and mechanisms, including the influence of genetic and epigenetic factors, placental and embryonic development, maternal nutrition, sex hormones, energy metabolism, microbiota, oxidative stress, cell death, inflammation, endothelial dysfunction, circadian rhythm, and lifestyle factors. Finally, we discuss some of the main therapeutic approaches, responses to which may be influenced by sexual dimorphism, such as antihypertensive and cardiovascular treatments, oxidative stress management, nutrition, cell therapies, and hormone replacement therapy.
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Affiliation(s)
| | | | | | | | | | | | | | - Catherine Yzydorczyk
- Developmental Origins of Health and Disease (DOHaD) Laboratory, Division of Pediatrics, Department Woman-Mother-Child, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland; (T.C.); (M.D.); (L.F.); (M.S.M.); (A.S.); (N.S.)
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Zheng J, Zhao L, Zhang Y, He W, Guo X, Wang J. Melatonin alleviates high glucose-induced cardiomyocyte injury through suppressing mitochondrial FUNDC1-DRP1 axis. J Pharm Pharmacol 2024; 76:1431-1448. [PMID: 39306802 DOI: 10.1093/jpp/rgae114] [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: 03/06/2024] [Accepted: 08/21/2024] [Indexed: 11/05/2024]
Abstract
OBJECTIVES To use H9c2 cardiomyocytes to establish a diabetic cardiomyopathic model by exposing these cells to high glucose (HG), followed by treating them with melatonin (MEL) or plasmid vectors overexpressing FUN14 Domain Containing 1 (FUNDC1). METHODS We employed quantitative real-time PCR, mitochondrial staining, and biochemical assays to measure the activity of various antioxidant and mitochondrial complex functions under various treatment conditions. KEY FINDINGS Our results showed that HG induced the expression of FUNDC1 and increased mitochondrial oxidative stress and fragmentation, while MEL treatment reversed most of these pathological effects. Moreover, HG exposure activated dynamin-related protein 1 expression and its translocation to mitochondria. Modulation of AMP-activated protein kinase level was found to be another pathological hallmark. In silico molecular docking, analysis revealed that MEL could directly bind the catalytic groove of FUNDC1 through Van der Waal's force and hydrogen bonding. Finally, MEL ameliorated diabetic cardiomyopathy-induced mitochondrial injury through FUNDC1 in vivo. CONCLUSIONS Hyperglycemia induced mitochondrial fragmentation and altered electron transport chain complex functions, which could be ameliorated by MEL treatment, suggesting its potential as a cardiovascular therapeutic.
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Affiliation(s)
- Junyi Zheng
- Department of Cardiology, Tianjin Chest Hospital, Tianjin 300222, China
- Department of Cardiology, Chest Hospital, Tianjin University, Tianjin 300222, China
- Clinical School of Thoracic, Tianjin Medical University, Tianjin 300222, China
- Tianjin Institute of Cardiovascular Disease, Tianjin 300222, China
| | - Lili Zhao
- Department of Cardiology, Tianjin Chest Hospital, Tianjin 300222, China
- Department of Cardiology, Chest Hospital, Tianjin University, Tianjin 300222, China
- Clinical School of Thoracic, Tianjin Medical University, Tianjin 300222, China
- Tianjin Institute of Cardiovascular Disease, Tianjin 300222, China
| | - Yingying Zhang
- Department of Cardiology, Tianjin Chest Hospital, Tianjin 300222, China
- Department of Cardiology, Chest Hospital, Tianjin University, Tianjin 300222, China
- Clinical School of Thoracic, Tianjin Medical University, Tianjin 300222, China
- Tianjin Institute of Cardiovascular Disease, Tianjin 300222, China
| | - Wenbin He
- Department of Cardiology, Tianjin Chest Hospital, Tianjin 300222, China
- Department of Cardiology, Chest Hospital, Tianjin University, Tianjin 300222, China
- Clinical School of Thoracic, Tianjin Medical University, Tianjin 300222, China
- Tianjin Institute of Cardiovascular Disease, Tianjin 300222, China
| | - Xukun Guo
- Department of Cardiology, Tianjin Chest Hospital, Tianjin 300222, China
- Department of Cardiology, Chest Hospital, Tianjin University, Tianjin 300222, China
- Clinical School of Thoracic, Tianjin Medical University, Tianjin 300222, China
- Tianjin Institute of Cardiovascular Disease, Tianjin 300222, China
| | - Jixiang Wang
- Department of Cardiology, Tianjin Chest Hospital, Tianjin 300222, China
- Department of Cardiology, Chest Hospital, Tianjin University, Tianjin 300222, China
- Clinical School of Thoracic, Tianjin Medical University, Tianjin 300222, China
- Tianjin Institute of Cardiovascular Disease, Tianjin 300222, China
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Nelakuditi B, Dandamudi BJ, Dimaano KAM, Shah N, AlQassab O, Al-Sulaitti Z, Khan S. Efficacy of Melatonin as a Promising Intervention for Migraine Prevention: A Systematic Review of Randomized Control Trials. Cureus 2024; 16:e72559. [PMID: 39606511 PMCID: PMC11601882 DOI: 10.7759/cureus.72559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Accepted: 10/26/2024] [Indexed: 11/29/2024] Open
Abstract
The availability and use of melatonin as an over-the-counter supplement have surged significantly in recent years due to the increased prevalence of sleep-wake disorders, notably in the post-COVID-19 era. While melatonin is known for managing insomnia, its applications extend beyond that. Its anti-inflammatory, antioxidant, and analgesic properties, along with increased usage, have garnered significant interest from researchers, particularly regarding its use in migraine prophylaxis and treatment. The aim of this systematic review is to evaluate the role of melatonin as prophylactic therapy for migraine, focusing on the efficacy and side effect profile of melatonin compared to standard therapy and placebo. Six databases were searched through June 2024, identifying 735 relevant articles. Only full-text randomized control trials involving humans, written or translated into English, were included in the study. Data were extracted, screened, sought for retrieval, and assessed for quality appraisal using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2). A total of seven randomized control trials involving 1,283 participants who met the eligibility criteria and passed the quality appraisal have been included in the study. All seven trials included patients diagnosed with migraine who were treated with either melatonin or agomelatine and were compared to those treated with conventional prophylactic therapy or placebo. The findings of this review suggest that melatonin significantly reduces the frequency and severity of migraines, but its dose-dependent action and benefits remain debatable. Melatonin may also have a role in weight control, warranting additional research in this direction.
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Affiliation(s)
- Bhavana Nelakuditi
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Bindu Jyothi Dandamudi
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Kathrina Antheia M Dimaano
- Obstetrics and Gynecology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Nensi Shah
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Osamah AlQassab
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Zainab Al-Sulaitti
- Obstetrics and Gynecology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Safeera Khan
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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4
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Martins TMDM, Ferrari FR, de Queiroz AA, Dalcin LDL, França DCH, Honório-França AC, França EL, Fagundes-Triches DLG. The Role of Melatonin in the Inflammatory Process in Patients with Hyperglycemia and Leishmania Infection. Biomolecules 2024; 14:950. [PMID: 39199338 PMCID: PMC11352828 DOI: 10.3390/biom14080950] [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: 07/06/2024] [Revised: 08/02/2024] [Accepted: 08/05/2024] [Indexed: 09/01/2024] Open
Abstract
Type 2 diabetes mellitus is a metabolic disorder that causes chronic high blood sugar levels, and diabetic patients are more susceptible to infections. American cutaneous leishmaniasis is an infectious disease caused by a parasite that affects the skin and mucous membranes, leading to one or multiple ulcerative lesions. Chronic inflammation and functional changes in various organs and systems, including the immune system, are the primary causes of both diseases. Melatonin, an essential immunomodulatory, antioxidant, and neuroprotective agent, can benefit many immunological processes and infectious diseases, including leishmaniasis. Although, limited reports are available on diabetic patients with leishmaniasis. The literature suggests that melatonin may play a promising role in inflammatory disorders. This study was designed to assess melatonin levels and inflammatory mediators in diabetic patients affected by leishmaniasis. Blood samples from 25 individuals were analyzed and divided into four groups: a control group (without any diseases), a Leishmania-positive group, patients with type 2 diabetes mellitus, and patients with a combination of both diseases. This study measured the serum levels of melatonin through ELISA, while IL-4 and TNF-α were measured using flow cytometry, and C-reactive protein was measured through turbidimetry. This study found that patients with leishmaniasis significantly increased TNF-α and decreased melatonin levels. However, the group of diabetic patients with leishmaniasis showed higher melatonin levels than the control group. These observations suggest that TNF-α may influence melatonin production in patients with American cutaneous leishmaniasis, potentially contributing to the inflammatory characteristics of both diseases.
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Affiliation(s)
| | | | | | | | | | | | - Eduardo Luzía França
- Institute of Biological and Health Science, Federal University of Mato Grosso, Barra do Garças 78605-091, MT, Brazil; (T.M.d.M.M.); (F.R.F.); (A.A.d.Q.); (L.D.L.D.); (D.C.H.F.); (D.L.G.F.-T.)
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Moghadam Fard A, Goodarzi P, Mottahedi M, Garousi S, Zadabhari H, Kalantari Shahijan M, Esmaeili S, Nabi-Afjadi M, Yousefi B. Therapeutic applications of melatonin in disorders related to the gastrointestinal tract and control of appetite. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:5335-5362. [PMID: 38358468 DOI: 10.1007/s00210-024-02972-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Accepted: 01/19/2024] [Indexed: 02/16/2024]
Abstract
Most animals have large amounts of the special substance melatonin, which is controlled by the light/dark cycle in the suprachiasmatic nucleus. According to what is now understood, the gastrointestinal tract (GIT) and other areas of the body are sites of melatonin production. According to recent studies, the GIT and adjacent organs depend critically on a massive amount of melatonin. Not unexpectedly, melatonin's many biological properties, such as its antioxidant, anti-inflammatory, pro-apoptotic, anti-proliferative, anti-metastasis, and antiangiogenic properties, have drawn the attention of researchers more and more. Because melatonin is an antioxidant, it produces a lot of secretions in the GIT's mucus and saliva, which shields cells from damage and promotes the development of certain GIT-related disorders. Melatonin's ability to alter cellular behavior in the GIT and other associated organs, such as the liver and pancreas, is another way that it functions. This behavior alters the secretory and metabolic activities of these cells. In this review, we attempted to shed fresh light on the many roles that melatonin plays in the various regions of the gastrointestinal tract by focusing on its activities for the first time.
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Affiliation(s)
| | - Pardis Goodarzi
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mehran Mottahedi
- Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Setareh Garousi
- Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamed Zadabhari
- Physiotherapy and Rehabilitation Faculty, Medipol University Health of Science, Istanbul, Turkey
| | | | - Saeedeh Esmaeili
- Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mohsen Nabi-Afjadi
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
| | - Bahman Yousefi
- Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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6
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Alam MJ, Kamboj P, Sarkar S, Gupta SK, Kasarla SS, Bajpai S, Kumari D, Bisht N, Barge SR, Kashyap B, Deka B, Bharadwaj S, Rahman S, Dutta PP, Borah JC, Talukdar NC, Kumar Y, Banerjee SK. Untargeted metabolomics and phenotype data indicate the therapeutic and prophylactic potential of Lysimachia candida Lindl. towards high-fat high-fructose-induced metabolic syndrome in rats. Mol Omics 2023; 19:787-799. [PMID: 37534494 DOI: 10.1039/d3mo00104k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2023]
Abstract
The present study evaluated the therapeutic potential of the medicinal plant Lysimachia candida Lindl. against metabolic syndrome in male SD rats fed with a high-fat high-fructose (HFHF) diet. Methanolic extract of Lysimachia candida Lindl. (250 mg kg-1 body weight p.o.) was administrated to the HFHF-fed rats daily for 20 weeks. Blood samples were collected, and blood glucose levels and relevant biochemical parameters were analysed and used for the assessment of metabolic disease phenotypes. In this study, Lysimachia candida decreased HFHF diet-induced phenotypes of metabolic syndrome, i.e., obesity, blood glucose level, hepatic triglycerides, free fatty acids, and insulin resistance. Liquid chromatography-mass spectrometry-based metabolomics was done to study the dynamics of metabolic changes in the serum during disease progression in the presence and absence of the treatment. Furthermore, multivariate data analysis approaches have been employed to identify metabolites responsible for disease progression. Lysimachia candida Lindl. plant extract restored the metabolites that are involved in the biosynthesis and degradation of amino acids, fatty acid metabolism and vitamin metabolism. Interestingly, the results depicted that the treatment with the plant extract restored the levels of acetylated amino acids and their derivatives, which are involved in the regulation of beta cell function, glucose homeostasis, insulin secretion, and metabolic syndrome phenotypes. Furthermore, we observed restoration in the levels of indole derivatives and N-acetylgalactosamine with the treatment, which indicates a cross-talk between the gut microbiome and the metabolic syndrome. Therefore, the present study revealed the potential mechanism of Lysimachia candida Lindl. extract to prevent metabolic syndrome in rats.
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Affiliation(s)
- Md Jahangir Alam
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati - 781101, Assam, India.
- Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India
| | - Parul Kamboj
- Non-communicable Disease Group, Translational Health Science and Technology Institute (THSTI), Faridabad - 121001, Haryana, India.
| | - Soumalya Sarkar
- Non-communicable Disease Group, Translational Health Science and Technology Institute (THSTI), Faridabad - 121001, Haryana, India.
| | - Sonu Kumar Gupta
- Non-communicable Disease Group, Translational Health Science and Technology Institute (THSTI), Faridabad - 121001, Haryana, India.
| | - Siva Swapna Kasarla
- Non-communicable Disease Group, Translational Health Science and Technology Institute (THSTI), Faridabad - 121001, Haryana, India.
| | - Sneh Bajpai
- Non-communicable Disease Group, Translational Health Science and Technology Institute (THSTI), Faridabad - 121001, Haryana, India.
| | - Deepika Kumari
- Non-communicable Disease Group, Translational Health Science and Technology Institute (THSTI), Faridabad - 121001, Haryana, India.
| | - Neema Bisht
- Non-communicable Disease Group, Translational Health Science and Technology Institute (THSTI), Faridabad - 121001, Haryana, India.
| | - Sagar Ramrao Barge
- Institute of Advanced Study in Science and Technology (IASST), Vigyan Path, Paschim Boragaon, Garchuk, Guwahati - 781035, Assam, India.
| | - Bhaswati Kashyap
- Institute of Advanced Study in Science and Technology (IASST), Vigyan Path, Paschim Boragaon, Garchuk, Guwahati - 781035, Assam, India.
| | - Barsha Deka
- Institute of Advanced Study in Science and Technology (IASST), Vigyan Path, Paschim Boragaon, Garchuk, Guwahati - 781035, Assam, India.
| | - Simanta Bharadwaj
- Institute of Advanced Study in Science and Technology (IASST), Vigyan Path, Paschim Boragaon, Garchuk, Guwahati - 781035, Assam, India.
| | - Seydur Rahman
- Institute of Advanced Study in Science and Technology (IASST), Vigyan Path, Paschim Boragaon, Garchuk, Guwahati - 781035, Assam, India.
| | - Partha Pratim Dutta
- Institute of Advanced Study in Science and Technology (IASST), Vigyan Path, Paschim Boragaon, Garchuk, Guwahati - 781035, Assam, India.
- Assam Down Town University, Panikhaiti, Guwahati - 781006, Assam, India
| | - Jagat C Borah
- Institute of Advanced Study in Science and Technology (IASST), Vigyan Path, Paschim Boragaon, Garchuk, Guwahati - 781035, Assam, India.
| | - Narayan Chandra Talukdar
- Institute of Advanced Study in Science and Technology (IASST), Vigyan Path, Paschim Boragaon, Garchuk, Guwahati - 781035, Assam, India.
- Assam Down Town University, Panikhaiti, Guwahati - 781006, Assam, India
| | - Yashwant Kumar
- Non-communicable Disease Group, Translational Health Science and Technology Institute (THSTI), Faridabad - 121001, Haryana, India.
| | - Sanjay K Banerjee
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati - 781101, Assam, India.
- Non-communicable Disease Group, Translational Health Science and Technology Institute (THSTI), Faridabad - 121001, Haryana, India.
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Patel A, Dewani D, Jaiswal A, Yadav P, Reddy LS. Exploring Melatonin's Multifaceted Role in Polycystic Ovary Syndrome Management: A Comprehensive Review. Cureus 2023; 15:e48929. [PMID: 38106751 PMCID: PMC10725523 DOI: 10.7759/cureus.48929] [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: 10/27/2023] [Accepted: 11/07/2023] [Indexed: 12/19/2023] Open
Abstract
Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder affecting a significant portion of the female population, characterized by hormonal imbalances, oxidative stress, sleep disturbances, and mood disorders. This review explores the multifaceted role of melatonin, a hormone primarily known for regulating circadian rhythms, in PCOS management. Melatonin's potential impact on hormonal balance, oxidative stress, sleep quality, and mood is comprehensively examined. It has been shown to enhance insulin sensitivity, regulate sex hormones, and influence gonadotropins, offering promise in addressing the intricate hormonal imbalances common in PCOS. As a potent antioxidant and anti-inflammatory agent, melatonin mitigates oxidative stress and its associated complications. Its role in improving sleep quality and mood can significantly enhance the psychological well-being and daily functioning of PCOS patients. We discuss the potential implications of melatonin as a complementary or adjunct therapy, alongside existing PCOS treatments, and its significance in improving the overall quality of life for individuals with this syndrome. While further research is needed, melatonin's multifaceted effects promise a brighter future for PCOS patients.
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Affiliation(s)
- Archan Patel
- Obstetrics and Gynaecology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Deepika Dewani
- Obstetrics and Gynaecology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Arpita Jaiswal
- Obstetrics and Gynaecology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Pallavi Yadav
- Obstetrics and Gynaecology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Lucky Srivani Reddy
- Obstetrics and Gynaecology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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Hariri A, Mirian M, Zarrabi A, Kohandel M, Amini-Pozveh M, Aref AR, Tabatabaee A, Prabhakar PK, Sivakumar PM. The circadian rhythm: an influential soundtrack in the diabetes story. Front Endocrinol (Lausanne) 2023; 14:1156757. [PMID: 37441501 PMCID: PMC10333930 DOI: 10.3389/fendo.2023.1156757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 05/03/2023] [Indexed: 07/15/2023] Open
Abstract
Type 2 Diabetes Mellitus (T2DM) has been the main category of metabolic diseases in recent years due to changes in lifestyle and environmental conditions such as diet and physical activity. On the other hand, the circadian rhythm is one of the most significant biological pathways in humans and other mammals, which is affected by light, sleep, and human activity. However, this cycle is controlled via complicated cellular pathways with feedback loops. It is widely known that changes in the circadian rhythm can alter some metabolic pathways of body cells and could affect the treatment process, particularly for metabolic diseases like T2DM. The aim of this study is to explore the importance of the circadian rhythm in the occurrence of T2DM via reviewing the metabolic pathways involved, their relationship with the circadian rhythm from two perspectives, lifestyle and molecular pathways, and their effect on T2DM pathophysiology. These impacts have been demonstrated in a variety of studies and led to the development of approaches such as time-restricted feeding, chronotherapy (time-specific therapies), and circadian molecule stabilizers.
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Affiliation(s)
- Amirali Hariri
- Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mina Mirian
- Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ali Zarrabi
- Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul, Türkiye
| | - Mohammad Kohandel
- Department of Applied Mathematics, Faculty of Mathematics, University of Waterloo, Waterloo, ON, Canada
| | - Maryam Amini-Pozveh
- Department of Prosthodontics Dentistry, Dental Materials Research Center, Dental Research Institute, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Amir Reza Aref
- Belfer Center for Applied Cancer Science, Dana Farber Cancer Institute, Boston, MA, United States
- Translational Sciences, Xsphera Biosciences Inc., Boston, MA, United States
| | - Aliye Tabatabaee
- School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Pranav Kumar Prabhakar
- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Lovely Professional University, Phagwara, Punjab, India
- Division of Research and Development, Lovely Professional University, Phagwara Punjab, India
| | - Ponnurengam Malliappan Sivakumar
- Institute of Research and Development, Duy Tan University, Da Nang, Vietnam
- School of Medicine and Pharmacy, Duy Tan University, Da Nang, Vietnam
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Hedayati N, Yaghoobi A, Salami M, Gholinezhad Y, Aghadavood F, Eshraghi R, Aarabi MH, Homayoonfal M, Asemi Z, Mirzaei H, Hajijafari M, Mafi A, Rezaee M. Impact of polyphenols on heart failure and cardiac hypertrophy: clinical effects and molecular mechanisms. Front Cardiovasc Med 2023; 10:1174816. [PMID: 37293283 PMCID: PMC10244790 DOI: 10.3389/fcvm.2023.1174816] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 05/02/2023] [Indexed: 06/10/2023] Open
Abstract
Polyphenols are abundant in regular diets and possess antioxidant, anti-inflammatory, anti-cancer, neuroprotective, and cardioprotective effects. Regarding the inadequacy of the current treatments in preventing cardiac remodeling following cardiovascular diseases, attention has been focused on improving cardiac function with potential alternatives such as polyphenols. The following online databases were searched for relevant orginial published from 2000 to 2023: EMBASE, MEDLINE, and Web of Science databases. The search strategy aimed to assess the effects of polyphenols on heart failure and keywords were "heart failure" and "polyphenols" and "cardiac hypertrophy" and "molecular mechanisms". Our results indicated polyphenols are repeatedly indicated to regulate various heart failure-related vital molecules and signaling pathways, such as inactivating fibrotic and hypertrophic factors, preventing mitochondrial dysfunction and free radical production, the underlying causes of apoptosis, and also improving lipid profile and cellular metabolism. In the current study, we aimed to review the most recent literature and investigations on the underlying mechanism of actions of different polyphenols subclasses in cardiac hypertrophy and heart failure to provide deep insight into novel mechanistic treatments and direct future studies in this context. Moreover, due to polyphenols' low bioavailability from conventional oral and intravenous administration routes, in this study, we have also investigated the currently accessible nano-drug delivery methods to optimize the treatment outcomes by providing sufficient drug delivery, targeted therapy, and less off-target effects, as desired by precision medicine standards.
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Affiliation(s)
- Neda Hedayati
- School of Medicine, Iran University of Medical Science, Tehran, Iran
| | - Alireza Yaghoobi
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Marziyeh Salami
- Department of Clinical Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Yasaman Gholinezhad
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farnaz Aghadavood
- Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Reza Eshraghi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Mohammad-Hossein Aarabi
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mina Homayoonfal
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Mohammad Hajijafari
- Department of Anesthesiology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Alireza Mafi
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
- Nutrition and Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Malihe Rezaee
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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Pinjari OF, Jones GH, Vecera CM, Smith K, Barrera A, Machado-Vieira R. The Role of the Gut Microbiome in Bipolar Disorder and its Common Comorbidities. Front Neuroendocrinol 2023:101078. [PMID: 37220806 DOI: 10.1016/j.yfrne.2023.101078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 04/13/2023] [Accepted: 05/19/2023] [Indexed: 05/25/2023]
Abstract
Bipolar disorder is a decidedly heterogeneous and multifactorial disease, with significant psychosocial and medical disease burden. Much difficulty has been encountered in developing novel therapeutics and objective biomarkers for clinical use in this population. In that regard, gut-microbial homeostasis appears to modulate several key pathways relevant to a variety of psychiatric, metabolic, and inflammatory disorders. Microbial impact on immune, endocrine, endocannabinoid, kynurenine, and other pathways are discussed throughout this review. Emphasis is placed on this system's relevance to current pharmacology, diet, and comorbid illness in bipolar disorder. Despite the high level of optimism promoted in many reviews on this topic, substantial obstacles exist before any microbiome-related findings can provide meaningful clinical utility. Beyond a comprehensive overview of pathophysiology, this review hopes to highlight several key areas where progress is needed. As well, novel microbiome-associated suggestions are presented for future research.
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Affiliation(s)
- Omar F Pinjari
- Wayne Scott (J-IV) Unit of Correctional Managed Care, University of Texas Medical Branch.
| | - Gregory H Jones
- Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston (UTHealth).
| | - Courtney M Vecera
- Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston (UTHealth).
| | - Kacy Smith
- Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston (UTHealth).
| | - Anita Barrera
- Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston (UTHealth).
| | - Rodrigo Machado-Vieira
- Wayne Scott (J-IV) Unit of Correctional Managed Care, University of Texas Medical Branch.
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11
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Mafi A, Keshavarzmotamed A, Hedayati N, Boroujeni ZY, Reiter RJ, Dehmordi RM, Aarabi MH, Rezaee M, Asemi Z. Melatonin targeting non-coding RNAs in cancer: Focus on mechanisms and potential therapeutic targets. Eur J Pharmacol 2023; 950:175755. [PMID: 37119959 DOI: 10.1016/j.ejphar.2023.175755] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 04/15/2023] [Accepted: 04/26/2023] [Indexed: 05/01/2023]
Abstract
Despite, melatonin is mainly known as a regulatory factor for circadian rhythm, its notable role in other fundamental biological processes, such as redox homeostasis and programmed cell death, has been found. In this line, a growing body of evidence indicated that melatonin could apply an inhibitory effect on the tumorigenic processes. Hence, melatonin might be considered an efficient adjuvant agent for cancer treatment. Besides, the physiological and pathological functions of non-coding RNAs (ncRNAs) in various disease, particularly cancers, have been expanded over the past two decades. It is well-established that ncRNAs can modulate the gene expression at various levels, thereby, ncRNAs. can regulate the numerous biological processes, including cell proliferation, cell metabolism, apoptosis, and cell cycle. Recently, targeting the ncRNAs expression provides a novel insight in the therapeutic approaches for cancer treatment. Moreover, accumulating investigations have revealed that melatonin could impact the expression of different ncRNAs in a multiple disorders, including cancer. Therefore, in the precent study, we discuss the potential roles of melatonin in modulating the expression of ncRNAs and the related molecular pathways in different types of cancer. Also, we highlighted its importance in therapeutic application and translational medicine in cancer treatment.
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Affiliation(s)
- Alireza Mafi
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran; Nutrition and Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
| | | | - Neda Hedayati
- School of Medicine, Iran University of Medical Science, Tehran, Iran.
| | - Zahra Yeganeh Boroujeni
- School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Russel J Reiter
- Department of Cell Systems and Anatomy, UT Health. Long School of Medicine, San Antonio, TX, USA.
| | - Rohollah Mousavi Dehmordi
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Mohammad-Hossein Aarabi
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Malihe Rezaee
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
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12
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Zilli Vieira CL, Koutrakis P, Liu M, Gottlieb DJ, Garshick E. Intense solar activity reduces urinary 6-sulfatoxymelatonin in patients with COPD. Respir Res 2023; 24:91. [PMID: 36959654 PMCID: PMC10037776 DOI: 10.1186/s12931-023-02390-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 03/08/2023] [Indexed: 03/25/2023] Open
Abstract
BACKGROUND Little is known about the link between solar activity and variations in melatonin. In this study, we investigated if melatonin's major urinary metabolite, urinary 6-sulfatoxymelatonin (aMT6s), is lowest under periods of intense solar activity. METHODS We investigated associations between high-energy solar particle events [Coronal Mass Ejection (CME) mass, speed and energy] on creatinine-adjusted aMT6s (aMT6sr) concentrations in 140 patients with chronic obstructive pulmonary disease (COPD) using up to four seasonal urine samples (n = 440). Mixed effect models with a random intercept for each subject were used to estimate associations, including effect modification attributable to diabetes, obesity, and reduced pulmonary function. RESULTS Higher values of CME were associated with reduced aMT6sr concentrations, with stronger associations in patients with diabetes. An interquartile range (IQR) increase in natural log CMEspeed averaged through two days before urine collection was associated with a reduction of 9.3% aMT6sr (95%CI: - 17.1%, - 0.8%) in aMT6sr. There was a greater reduction in aMT6sr in patients with diabetes (- 24.5%; 95%CI: - 35.9%, - 11.6%). In patients without diabetes there was no meaningful association (- 2.2%; 95%CI: - 12%, 8.4%). There were similar associations with CMEenergy and CMEmass. There was no effect modification attributable to reduced pulmonary function or obesity. CONCLUSIONS This is the first study in patients with COPD to demonstrate strong detrimental impact of high-energy solar particle events on aMT6sr, with greater associations in patients with diabetes. Since melatonin is an anti-oxidant, it is possible that adverse effects of intense solar activity may be attributable to a reduction in circulating melatonin and that patients with both COPD and diabetes may be more susceptible.
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Affiliation(s)
- Carolina L. Zilli Vieira
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, 401 Park Drive, Landmark Center Room 420, Boston, MA 02115 USA
| | - Petros Koutrakis
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, 401 Park Drive, Landmark Center Room 420, Boston, MA 02115 USA
| | - Man Liu
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, 401 Park Drive, Landmark Center Room 420, Boston, MA 02115 USA
| | - Daniel J. Gottlieb
- Pulmonary, Allergy, Sleep and Critical Care Medicine Section, Veterans Affairs Boston Healthcare System, Boston, MA USA
- Harvard Medical School, Boston, MA USA
| | - Eric Garshick
- Pulmonary, Allergy, Sleep and Critical Care Medicine Section, Veterans Affairs Boston Healthcare System, Boston, MA USA
- Harvard Medical School, Boston, MA USA
- Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA USA
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13
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Tang YL, Zhu L, Tao Y, Lu W, Cheng H. Role of targeting TLR4 signaling axis in liver-related diseases. Pathol Res Pract 2023; 244:154410. [PMID: 36917917 DOI: 10.1016/j.prp.2023.154410] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 03/05/2023] [Accepted: 03/06/2023] [Indexed: 03/09/2023]
Abstract
Toll-like receptor 4 (TLR4) plays an important role as a key signal-receiving transmembrane protein molecule in the liver, and substances that target the liver exert therapeutic effects via TLR4-related signaling pathways. This article provides a comprehensive review of targeting the TLR4 signaling axis to play an important role in the liver based on endogenous substances. Articles were divided into 5 major types of liver disease, acute liver injury, viral hepatitis, alcoholic and non-alcoholic liver disease, cirrhosis, and liver cancer, to elucidate how various endogenous substances affect the liver via the TLR4 pathway and the important role of the pathway itself in liver-related diseases to discover the potential therapeutic implications of the TLR4-related pathway in the liver. The results indicate that activation of the TLR4-related signaling axis primarily plays a role in promoting disease progression in liver-related diseases, and the TLR4/MyD88/NF-κB axis plays the most dominant role. Therefore, exploring the full effects of drugs targeting the TLR4-related signaling axis in the liver and the new use of old drugs may be a new research direction.
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Affiliation(s)
- Ying-Le Tang
- Medical College, Yangzhou University, Yangzhou, China
| | - Lin Zhu
- Medical College, Yangzhou University, Yangzhou, China
| | - Yan Tao
- Medical College, Yangzhou University, Yangzhou, China
| | - Wen Lu
- Medical College, Yangzhou University, Yangzhou, China
| | - Hong Cheng
- Yangzhou University Medical College, Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Institute of Translational Medicine, Yangzhou University, Jiangsu, Yangzhou, China.
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Partsernyak AS, Polyakova VO, Trufanov AG, Medvedev DS, Trotsyuk DV, Markin K, Kurasov ES, Kuznetsova EV, Krasichkov AS. Melatonin: Manager of psychosomatic and metabolic disorders in polymorbid cardiovascular pathology. Front Neurosci 2022; 16:989497. [PMID: 36248667 PMCID: PMC9554144 DOI: 10.3389/fnins.2022.989497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 09/12/2022] [Indexed: 11/13/2022] Open
Abstract
Objectives To investigate the relationship between changes in circadian patterns of melatonin and clinical manifestations of polymorbid cardiovascular pathology (PCVP) in young men and to analyze the effectiveness of their complex treatment. Materials and methods We made the immunohistochemical (IHC) analysis of epiphysis tissues from autopsies of 25 men aged 32–44 with PCVP and metabolic syndrome (MS) who had died as a result of ischemic cardiomyopathy (IC) and 25 persons after the car accident as a control group. Then, 93 young men aged 35–44 with PCVP, metabolic syndrome, and depressive spectrum disorders (DSD) were divided into three groups: (1) standard therapy; (2) standard therapy and psychotherapy sessions; (3) standard therapy in combination with psychotherapeutic and psychophysiological visual and auditory correction sessions. The control group included 24 conditionally healthy male volunteers. Before and after the treatment, we studied the anthropometric status, lipid and carbohydrate metabolism indicators, the level of urinary 6-hydroxymelatonin sulfate, the degree of nocturnal decrease in blood pressure (BP), and the relationship of these indicators with circadian variations of melatonin excretion. Results Young polymorbid patients who died from IC have a lower expression of melatonin type 1 and 2 receptors. All patients with PCVP showed a decrease in the nocturnal melatonin excretion fraction and a correlation with higher severity of depressive (r = −0.72) and anxiety (r = −0.66) symptoms. Reduced values of the 6-hydroxymelatonin sulfate (6-SM) in the 1st (r = 0.45), 2nd (r = 0.39), and 3rd (r = 0.51) groups before treatment was associated with periods of increased BP. The achievement of melatonin excretion reference values and normalization of biochemical parameters of carbohydrate and lipid metabolism, daily BP profile, and psychophysiological state were noted in all three patients’ groups, with a more pronounced effect in group 3. Conclusion Low nocturnal melatonin excretion levels are associated with greater severity of clinical symptoms and a higher risk of death in patients with PCVP. Therefore, comprehensive therapy may be more effective for correcting this disease.
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Affiliation(s)
- Alexander S. Partsernyak
- Department of Military Field Therapy, Kirov Military Medical Academy, Saint Petersburg, Russia
- *Correspondence: Alexander S. Partsernyak,
| | - Victoria O. Polyakova
- Center for Molecular Biomedicine, St. Petersburg Research Institute of Phthisiopulmonology, Saint Petersburg, Russia
| | - Artem G. Trufanov
- Department of Neurology, Kirov Military Medical Academy, Saint Petersburg, Russia
- Department of Software Engineering and Computer Applications, Saint Petersburg Electrotechnical University “LETI”, Saint Petersburg, Russia
| | - Dmitriy S. Medvedev
- Department of Physiological Assessment and Medical Correction, Research Institute of Hygiene, Occupational Pathology and Human Ecology of the Federal Medical Biological Agency of Russia, Kuzmolovsky, Russia
| | - Dina V. Trotsyuk
- Department of Internal Diseases, Private Educational Institution of Higher Education “St. Petersburg Medical and Social Institute”, Saint Petersburg, Russia
| | - Kirill Markin
- Department of Psychiatry, Kirov Military Medical Academy, Saint Petersburg, Russia
| | - Evgeniy S. Kurasov
- Department of Psychiatry, Kirov Military Medical Academy, Saint Petersburg, Russia
| | | | - Alexander S. Krasichkov
- Department of Radio Engineering Systems, Saint Petersburg Electrotechnical University “LETI”, Saint Petersburg, Russia
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15
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Hosseini A, Samadi M, Baeeri M, Rahimifard M, Haghi-Aminjan H. The neuroprotective effects of melatonin against diabetic neuropathy: A systematic review of non-clinical studies. Front Pharmacol 2022; 13:984499. [PMID: 36120309 PMCID: PMC9470957 DOI: 10.3389/fphar.2022.984499] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Accepted: 08/05/2022] [Indexed: 11/30/2022] Open
Abstract
Backgrounds: Diabetes can cause diabetic neuropathy (DN), a nerve injury. High blood sugar (glucose) levels can harm nerves all over your body. The nerves in your legs and feet are the most commonly affected by DN. The purpose of this study was to conduct a review of melatonin’s potential neuroprotective properties against DN. Method: A full systematic search was conducted in several electronic databases (Scopus, PubMed, and Web of Science) up to March 2022 under the PRISMA guidelines. Forty-seven studies were screened using predefined inclusion and exclusion criteria. Finally, the current systematic review included nine publications that met the inclusion criteria. Result: According to in vivo findings, melatonin treatment reduces DN via inhibition of oxidative stress and inflammatory pathways. However, compared to the diabetes groups alone, melatonin treatment exhibited an anti-oxidant trend. According to other research, DN also significantly produces biochemical alterations in neuron cells/tissues. Additionally, histological alterations in neuron tissue following DN were detected. Conclusion: Nonetheless, in the majority of cases, these diabetes-induced biochemical and histological alterations were reversed when melatonin was administered. It is worth noting that the administration of melatonin ameliorates the neuropathy caused by diabetes. Melatonin exerts these neuroprotective effects via various anti-oxidant, anti-inflammatory, and other mechanisms.
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Affiliation(s)
- Asieh Hosseini
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mahedeh Samadi
- Neuroscience Research Center, Iran University of Medical Science, Tehran, Iran
| | - Maryam Baeeri
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Mahban Rahimifard
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences (TUMS), Tehran, Iran
- *Correspondence: Mahban Rahimifard, ; Hamed Haghi-Aminjan,
| | - Hamed Haghi-Aminjan
- Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
- *Correspondence: Mahban Rahimifard, ; Hamed Haghi-Aminjan,
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Takahashi T, Wood SJ, Yung AR, Nelson B, Lin A, Yuen HP, Phillips LJ, Suzuki M, McGorry PD, Velakoulis D, Pantelis C. Pineal morphology of the clinical high-risk state for psychosis and different psychotic disorders. Schizophr Res 2022; 244:1-7. [PMID: 35487129 DOI: 10.1016/j.schres.2022.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 04/13/2022] [Accepted: 04/16/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND Pineal volume reductions have been reported in schizophrenia and clinical high-risk states for the development of psychosis, supporting the role of melatonin dysregulation in the pathophysiology of psychosis. However, it remains unclear whether pineal volume is associated with the later onset of psychosis in individuals at clinical high-risk (CHR) of psychosis or if pineal atrophy is specific to schizophrenia among different psychotic disorders. METHODS This magnetic resonance imaging study examined the volume of and cyst prevalence in the pineal gland in 135 individuals at CHR of psychosis [52 (38.5%) subsequently developed psychosis], 162 with first-episode psychosis (FEP), 89 with chronic schizophrenia, and 87 healthy controls. The potential contribution of the pineal morphology to clinical characteristics was also examined in the CHR and FEP groups. RESULTS Pineal volumes did not differ significantly between the CHR, FEP, and chronic schizophrenia groups, but were significantly smaller than that in healthy controls. However, pineal volumes were not associated with the later onset of psychosis in the CHR group or FEP sub-diagnosis (i.e., schizophrenia, schizophreniform disorder, affective psychosis, and other psychoses). No significant differences were observed in the prevalence of pineal cysts between the groups, and it also did not correlate with clinical characteristics in the CHR and FEP groups. CONCLUSION These results suggest that pineal atrophy is a general vulnerability marker of psychosis, while pineal cysts do not appear to contribute to the pathophysiology of psychosis.
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Affiliation(s)
- Tsutomu Takahashi
- Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan; Research Center for Idling Brain Science, University of Toyama, Toyama, Japan.
| | - Stephen J Wood
- Orygen, Melbourne, Australia; Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia; School of Psychology, University of Birmingham, Birmingham, UK
| | - Alison R Yung
- Orygen, Melbourne, Australia; Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia; Institute for Mental and Physical Health and Clinical Translation (IMPACT), Deakin University, Geelong, Australia; School of Health Sciences, University of Manchester, Manchester, UK
| | - Barnaby Nelson
- Orygen, Melbourne, Australia; Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia
| | - Ashleigh Lin
- Telethon Kids Institute, The University of Western Australia, Perth, Australia
| | | | - Lisa J Phillips
- Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Australia
| | - Michio Suzuki
- Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan; Research Center for Idling Brain Science, University of Toyama, Toyama, Japan
| | - Patrick D McGorry
- Orygen, Melbourne, Australia; Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia
| | - Dennis Velakoulis
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia; Neuropsychiatry, Royal Melbourne Hospital, Melbourne Health, Melbourne, Australia
| | - Christos Pantelis
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia; Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; North Western Mental Health, Western Hospital Sunshine, St. Albans, Victoria, Australia
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Liu PH, Chuang GT, Hsiung CN, Yang WS, Ku HC, Lin YC, Chen YS, Huang YY, Lin CH, Li WY, Lin JW, Hsu CN, Hwang JJ, Liao KCW, Hsieh ML, Lee HL, Shen CY, Chang YC. A genome-wide association study for melatonin secretion. Sci Rep 2022; 12:8025. [PMID: 35577822 PMCID: PMC9110427 DOI: 10.1038/s41598-022-12084-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 05/04/2022] [Indexed: 11/09/2022] Open
Abstract
AbstractMelatonin exerts a wide range of effects among various tissues and organs. However, there is currently no study to investigate the genetic determinants of melatonin secretion. Here, we conducted a genome-wide association study (GWAS) for melatonin secretion using morning urine 6-hydroxymelatonin sulfate-to-creatinine ratio (UMCR). We initially enrolled 5000 participants from Taiwan Biobank in this study. After excluding individuals that did not have their urine collected in the morning, those who had history of neurological or psychiatric disorder, and those who failed to pass quality control, association of single nucleotide polymorphisms with log-transformed UMCR adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for estimated glomerular filtration rate (eGFR). A total of 2373 participants underwent the genome-wide analysis. Five candidate loci associated with log UMCR (P value ranging from 6.83 × 10−7 to 3.44 × 10−6) encompassing ZFHX3, GALNT15, GALNT13, LDLRAD3 and intergenic between SEPP1 and FLJ32255 were identified. Similar results were yielded with further adjustment for eGFR. Interestingly, the identified genes are associated with circadian behavior, neuronal differentiation, motor disorders, anxiety, and neurodegenerative diseases. We conducted the first GWAS for melatonin secretion and identified five candidate genetic loci associated with melatonin level. Replication and functional studies are needed in the future.
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Hajam YA, Rai S, Pandi-Perumal SR, Brown GM, Reiter RJ, Cardinali DP. Coadministration of Melatonin and Insulin Improves Diabetes-Induced Impairment of Rat Kidney Function. Neuroendocrinology 2022; 112:807-822. [PMID: 34673653 DOI: 10.1159/000520280] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 10/18/2021] [Indexed: 11/19/2022]
Abstract
INTRODUCTION The present study was designed to evaluate the therapeutic efficacy of melatonin and insulin coadministration in diabetes-induced renal injury in rats. RESEARCH DESIGN AND METHODS Diabetes was achieved by giving streptozotocin (15 mg/kg) for 6 consecutive days. The diabetic condition was confirmed by assessing the blood glucose level; animals having blood glucose levels above 250 mg were considered as diabetic. Following the confirmation, animals were randomly divided into different experimental groups, viz group I served as the control (CON), group II diabetic (D), group III D+melatonin (MEL), group IV D+insulin (INS), group V D+MEL+INS, group VI D+glibenclamide (GB), group VII CON+MEL, group VIII CON+INS, and group IX CON+GB. Following the completion of the experimental period, animals were sacrificed, blood was collected via a retro-orbital puncture, and kidneys were harvested. Diabetic rats exhibited a significant increment in blood glucose and biochemical indexes of renal injury (tubular disruption, swollen glomeruli with loss of glomerular spaces, and distortion of the endothelial lining) including augmented levels of serum creatinine, urea, uric acid, Na+, and K+, and inhibition/suppression of the activity of glutathione (GSH) peroxidase, GSH reductase, glucose-6-phosphate dehydrogenase, and GSH-S-transferase in the renal cortex. RESULTS By examining thiobarbiturate reactive substances, reduced GSH, superoxide dismutase activity, and catalase activity in the renal cortex of control and diabetic rats, it was documented that treatment with melatonin or insulin alone or in combination showed a significant ad integrum recovery of GSH-dependent antioxidative enzymatic activities. Melatonin and insulin coadministration caused greater reductions in circulating tumor necrosis factor-α, tumor growth factor-β1, interleukin (IL)-1β, and IL-6 levels in diabetic rats, whereas IL-10 levels increased, as compared to each treatment alone. Diabetic rats showed a significant increase in the expression of both MT1 and MT2 melatonin receptor genes. Melatonin or insulin treatment alone or in combination resulted in significant restoration of the relative expression of both melatonin receptors in the renal cortex. CONCLUSION The coadministration of exogenous melatonin and insulin abolished many of the deleterious effects of type 1 diabetes on rat renal function.
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Affiliation(s)
- Younis Ahmad Hajam
- Department of Zoology, Guru Ghasidas Vishwavidayalaya (A Central University), Bilaspur, India
- Division Zoology, Department of Biosciences, Career Point University, Hamirpur, India
| | - Seema Rai
- Department of Zoology, Guru Ghasidas Vishwavidayalaya (A Central University), Bilaspur, India
| | - Seithikurippu R Pandi-Perumal
- Somnogen Canada Inc., Toronto, Ontario, Canada
- Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
| | - Gregory M Brown
- Department of Psychiatry, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
| | - Russel J Reiter
- Department of Cell Systems and Anatomy, UT Health San Antonio, Long School of Medicine, San Antonio, Texas, USA
| | - Daniel P Cardinali
- Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, Buenos Aires, Argentina
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Melatonin Alleviates LPS-Induced Pyroptotic Cell Death in Human Stem Cell-Derived Cardiomyocytes by Activating Autophagy. Stem Cells Int 2021; 2021:8120403. [PMID: 34873405 PMCID: PMC8643260 DOI: 10.1155/2021/8120403] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 10/22/2021] [Accepted: 10/29/2021] [Indexed: 11/18/2022] Open
Abstract
Endotoxemia in sepsis remains a problem due to a lack of effective strategies. Our previous studies have demonstrated that melatonin (Mel) protects against ischemic heart injury and arteriosclerosis. However, its role in endotoxemia-exposed cardiomyocytes remains poorly understood. This study explored, for the first time, the protective effect of Mel on the pyroptosis of human stem cell-derived cardiomyocytes (hiPSC-CMs) exposed to lipopolysaccharide (LPS). Our results showed that treatment with 1 μM or 10 μM Mel for 12 h significantly improved 1 μg/ml LPS-induced hiPSC-CM injuries, as reflected by drastically decreased LDH release and increased cell viability, which was accompanied by the overt induction of autophagy. Specifically, Mel profoundly alleviated LPS-induced cell pyroptosis, as evidenced by decreased propidium iodide (PI) and active caspase-1 double-positive cell rates; suppressed the expression of NLRP3, cleaved caspase-1 (activated form of caspase-1), and GSDMD-NT (functional N-terminal fragment of GSDMD) expression; and inhibited the production of the cleaved IL-1β and cleaved IL-18 cytokines. Additionally, double-membrane autophagosomes were observed in LPS-injured hiPSC-CMs treated with 1 μM or 10 μM Mel. The hiPSC-CMs treated with LPS exhibited considerably fewer acidic vesicles (as revealed by LAMP1 staining) and autophagosomes (as revealed by LC3-II staining); however, Mel reversed this outcome in a dose-dependent manner. Furthermore, coincubation with rapamycin (an autophagy activator) or 3-MA (an autophagy inhibitor) accentuated and attenuated the antipyroptotic actions of Mel, respectively. Collectively, our findings demonstrate that Mel shields hiPSC-CMs against pyroptosis during endotoxemia by activating autophagy.
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Yu Y, Chen D, Zhao Y, Zhu J, Dong X. Melatonin ameliorates hepatic steatosis by inhibiting NLRP3 inflammasome in db/db mice. Int J Immunopathol Pharmacol 2021; 35:20587384211036819. [PMID: 34399601 PMCID: PMC8375339 DOI: 10.1177/20587384211036819] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Introduction: Type 2 diabetes mellitus (T2DM) is commonly accompanied by obesity and non-alcoholic fatty liver disease (NAFLD), yet the mechanism underlying diabetes-related NAFLD is not fully understood. It has been reported that melatonin can regulate glucose and lipid metabolism. This study aims to investigate the actions and mechanisms of melatonin toward the development of diabetes-related NAFLD. Methods: Melatonin (bid, 30 mg/kg/day, i.p.) was administrated to db/db mice for 8 weeks, while saline was administrated to db/m mice. The metabolic parameters of mice were measured using an automatic biochemistry analyzer. The oxidative stress indexes and mitochondrial membrane potential (MMP) were determined with kits. Pathological assessment in liver tissues was used to analyze the effects of melatonin on hepatic steatosis. The levels of IL-1β and IL-18 were detected with ELISA kits. The mRNA levels of NLRP3 inflammasome were detected using quantitative real-time PCR assay, and protein expressions were estimated using Western blotting assay. Immunofluorescence staining was used to evaluate the caspase-1 expression in the liver. Results: Melatonin treatment significantly reduced blood glucose, serum insulin, body weight, related liver weight, serum lipids, and hepatic enzymes in db/db mice. Melatonin markedly corrected the NAFLD phenotypes, including lipid accumulation, steatohepatitis, fibrosis, and oxidative stress levels. Melatonin significantly improved the MMP level and decreased the serum IL-1β and IL-18 concentrations. The mRNA levels of the NLRP3 inflammasome could also be remarkably reversed by melatonin in the liver tissues. The activation of the NLRP3 inflammasome was also suppressed, evidenced by the downregulated proteins of NLRP3, caspase-1, IL-1β, and IL-18. The enhanced fluorescence intensity of caspase-1 in the liver tissues was also obviously weakened by the melatonin treatment. Conclusion: Our study concluded that melatonin could safeguard against NAFLD by improving hepatic steatosis in db/db mice, and this action could be associated with the regulation of the NLRP3 inflammasome activation.
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Affiliation(s)
- Yongxiang Yu
- Department of Pharmacy, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, China
| | - Dongru Chen
- Community Health Service Center of Suoqian Town, Hangzhou, China
| | - Yuhua Zhao
- Department of Pharmacy, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, China
| | - Jianjun Zhu
- Department of Pharmacy, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, China
| | - Xiaohui Dong
- Department of Pharmacy, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
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Geoffroy PA, Palagini L. Biological rhythms and chronotherapeutics in depression. Prog Neuropsychopharmacol Biol Psychiatry 2021; 106:110158. [PMID: 33152388 DOI: 10.1016/j.pnpbp.2020.110158] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 10/14/2020] [Accepted: 10/27/2020] [Indexed: 12/28/2022]
Abstract
Depressive syndromes are frequent and heterogeneous brain conditions with more than 90% of patients suffering from sleep complaints. Better characterizing this "sleep" domain may allow to both better treat acute episodes with existing chronotherapeutics, but also to prevent the manifestation or recurrences of mood disorders. This work aims to i) review theoretical and fundamental data of chronotherapeutics, and ii) provide practical recommendations. Light therapy (LT) can be used as a first-line monotherapy of moderate to severe depression of all subtypes. LT can be also used as a combination with antidepressant to maximize patients' response rates, which has a clear superiority to antidepressant alone. Sleep deprivation (SD) is a rapid and powerful chronotherapeutic with antidepressant responses within hours in 45-60% of patients with unipolar or bipolar depression. Different strategies should be combined to stabilize the SD antidepressant effect, including concomitant medications, repeated SD, combination with sleep phase advance and/or LT (triple chronotherapy). Melatonin treatment is of interest in remitted patients with mood disorder to prevent relapses or recurrences, if a complaint of insomnia, poor sleep quality or phase delay syndrome is associated. During the acute phase, melatonin could be used as an adjuvant treatment for symptoms of insomnia associated with depression. The cognitive behavioral therapy for insomnia (CBT-I) can be recommend to treat insomnia during euthymic phases. The Interpersonal and social rhythm therapy (IPSRT) is indicated for the acute treatment of bipolar depression and for the prevention of mood episodes. Chronotherapeutics should always be associated with behavioral measures for healthy sleep.
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Affiliation(s)
- Pierre A Geoffroy
- Département de psychiatrie et d'addictologie, AP-HP, GHU Paris Nord, DMU Neurosciences, Hopital Bichat - Claude Bernard, F-75018 Paris, France; GHU Paris - Psychiatry & Neurosciences, 1 rue Cabanis, 75014 Paris, France; Université de Paris, NeuroDiderot, Inserm, F-75019 Paris, France.
| | - Laura Palagini
- Department of Clinical and Experimental Medicine, Psychiatric Section, University of Pisa; Azienda Ospedaliera Universitaria Pisana (AUOP), Pisa, Italy
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Ozkalayci F, Kocabas U, Altun BU, Pandi-Perumal S, Altun A. Relationship Between Melatonin and Cardiovascular Disease. Cureus 2021; 13:e12935. [PMID: 33654615 PMCID: PMC7914336 DOI: 10.7759/cureus.12935] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality worldwide. The coronary atherosclerotic process involves different pathological mechanisms; inflammation is one of the major triggers for the development of atherosclerotic plaque. Although several studies showed the favorable effects of melatonin on the cardiovascular system (CVS), melatonin seems not to take its rightful place in today's clinical practice. This review aims to point out the role of melatonin on cardiovascular disease (CVD) and its' risk factors. All data were obtained via PubMed, Wikipedia, and Google.
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Affiliation(s)
| | - Umut Kocabas
- Cardiology, Baskent University Izmir Hospital, Izmir, TUR
| | | | | | - Armagan Altun
- Cardiology, Baskent University İstanbul Hospital, Istanbul, TUR
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Ünüvar S, Gürsoy Ş, Berk A, Kaymaz B, İlhan N, Aktay G. Antioxidant Effect of a Dihydropyridine
Calcium Antagonist Nitrendipine in Streptozotocin-Induced Diabetes. J EVOL BIOCHEM PHYS+ 2021. [DOI: 10.1134/s0022093021010129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Wajid F, Poolacherla R, Mim FK, Bangash A, Rutkofsky IH. Therapeutic potential of melatonin as a chronobiotic and cytoprotective agent in diabetes mellitus. J Diabetes Metab Disord 2020; 19:1797-1825. [PMID: 33520862 PMCID: PMC7843808 DOI: 10.1007/s40200-020-00585-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 07/06/2020] [Indexed: 12/21/2022]
Abstract
PURPOSE Diabetes mellitus is a complex metabolic disorder characterized by hyperglycemia occurring as a result of dysregulation and balance of various metabolic pathways. In recent years, circadian misalignment (due to altered sleep/wake, feeding/fasting cycles), has been intimately linked with the development of diabetes mellitus. Herein, we review our knowledge of oxidative stress, circadian rhythms control of metabolism, and the effects of its disruption on homeostasis while emphasizing the importance of melatonin, a nocturnally peaking, pineal hormone, as a potential therapeutic drug for the prevention and treatment of diabetes. METHODS PubMed database was systematically searched for related articles and data from all types of studies, including clinical trials, review articles, and case reports were considered without limiting the study to one specific category. RESULTS Experimental and epidemiological evidence indicate melatonin's multifaceted effects in intermediary metabolism via resynchronization of the circadian rhythms and its deficiency is associated with metabolic derangements. As a chronobiotic, it cures insomnia and sleep disorders caused by shift work or jet lag. The antagonistic relationship between melatonin and insulin highlights its influence in regulating insulin secretion, its action, and melatonin treatment successfully improved glucose homeostasis, energy balance, and overall health in diabetes mellitus. Melatonin's cytoprotective role as an antioxidant and free radical scavenger, proved useful in combating oxidative stress, preserving beta-cell function, and influencing the development of diabetic complications. CONCLUSION The therapeutic application of melatonin as a chronobiotic and cytoprotective agent is of promising significance in diabetes mellitus. Future investigations are encouraged to fully explore the efficacy of this ubiquitous molecule in various metabolic disorders.
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Affiliation(s)
- Fareha Wajid
- California Institute of Behavioural Neuroscience and Psychology, Fairfield, CA USA
| | - Raju Poolacherla
- California Institute of Behavioural Neuroscience and Psychology, Fairfield, CA USA
| | - Fatiha Kabir Mim
- California Institute of Behavioural Neuroscience and Psychology, Fairfield, CA USA
| | - Amna Bangash
- California Institute of Behavioural Neuroscience and Psychology, Fairfield, CA USA
| | - Ian H. Rutkofsky
- California Institute of Behavioural Neuroscience and Psychology, Fairfield, CA USA
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25
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Övey İS, Nazıroğlu M. Effects of homocysteine and memantine on oxidative stress related TRP cation channels in in-vitro model of Alzheimer’s disease. J Recept Signal Transduct Res 2020; 41:273-283. [DOI: 10.1080/10799893.2020.1806321] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Affiliation(s)
- İshak Suat Övey
- Department of Physiology, School of Medicine, Alanya Alaaddin Keykubat University, Alanya, Turkey
- Department of Neuroscience, Institute of Health Sciences, Suleyman Demirel University, Isparta, Turkey
| | - Mustafa Nazıroğlu
- Department of Neuroscience, Institute of Health Sciences, Suleyman Demirel University, Isparta, Turkey
- Neuroscience Research Center, Suleyman Demirel University, Isparta, Turkey
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Tiong YL, Ng KY, Koh RY, Ponnudurai G, Chye SM. Melatonin inhibits high glucose-induced ox-LDL/LDL expression and apoptosis in human umbilical endothelial cells. Horm Mol Biol Clin Investig 2020; 41:/j/hmbci.ahead-of-print/hmbci-2020-0009/hmbci-2020-0009.xml. [PMID: 32598308 DOI: 10.1515/hmbci-2020-0009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Accepted: 02/28/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Cardiovascular disease (CVD) is one of the major cause of mortality in diabetic patients. Evidence suggests that hyperglycemia in diabetic patients contributes to increased risk of CVD. This study is to investigate the therapeutic effects of melatonin on glucose-treated human umbilical vein endothelial cells (HUVEC) and provide insights on the underlying mechanisms. MATERIALS AND METHODS Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Reactive oxygen species (ROS) and membrane potential was detected using 2',7'-dichlorofluorescein diacetate and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1) dye staining, respectively. While, cell apoptosis was determined by Annexin-V staining and protein expression was measured using Western blot. RESULTS Our results suggested that melatonin inhibited glucose-induced ROS elevation, mitochondria dysfunction and apoptosis on HUVEC. Melatonin inhibited glucose-induced HUVEC apoptosis via PI3K/Akt signaling pathway. Activation of Akt further activated BcL-2 pathway through upregulation of Mcl-1 expression and downregulation Bax expression in order to inhibit glucose-induced HUVEC apoptosis. Besides that, melatonin promoted downregulation of oxLDL/LOX-1 in order to inhibit glucose-induced HUVEC apoptosis. CONCLUSIONS In conclusion, our results suggested that melatonin exerted vasculoprotective effects against glucose-induced apoptosis in HUVEC through PI3K/Akt, Bcl-2 and oxLDL/LOX-1 signaling pathways.
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Affiliation(s)
- Yee Lian Tiong
- School of Postgraduate, International Medical University, Kuala Lumpur 57000, Malaysia
| | - Khuen Yen Ng
- School of Pharmacy, Monash University Malaysia, Subang Jaya, Selangor 47500, Malaysia
| | - Rhun Yian Koh
- School of Health Science, Division of Biomedical Science and Biotechnology, International Medical University, 57000 Kuala Lumpur, Malaysia
| | | | - Soi Moi Chye
- School of Health Science, Division of Biomedical Science and Biotechnology, International Medical University, 57000 Kuala Lumpur, Malaysia
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Effects of melatonin on cardiovascular risk factors and metabolic syndrome: a comprehensive review. Naunyn Schmiedebergs Arch Pharmacol 2020; 393:521-536. [DOI: 10.1007/s00210-020-01822-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 01/10/2020] [Indexed: 12/13/2022]
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Tamtaji OR, Reiter RJ, Alipoor R, Dadgostar E, Kouchaki E, Asemi Z. Melatonin and Parkinson Disease: Current Status and Future Perspectives for Molecular Mechanisms. Cell Mol Neurobiol 2020; 40:15-23. [PMID: 31388798 PMCID: PMC11448849 DOI: 10.1007/s10571-019-00720-5] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Accepted: 07/31/2019] [Indexed: 12/29/2022]
Abstract
Parkinson disease (PD) is a chronic and neurodegenerative disease with motor and nonmotor symptoms. Multiple pathways are involved in the pathophysiology of PD, including apoptosis, autophagy, oxidative stress, inflammation, α-synuclein aggregation, and changes in the neurotransmitters. Preclinical and clinical studies have shown that melatonin supplementation is an appropriate therapy for PD. Administration of melatonin leads to inhibition of some pathways related to apoptosis, autophagy, oxidative stress, inflammation, α-synuclein aggregation, and dopamine loss in PD. In addition, melatonin improves some nonmotor symptom in patients with PD. Limited studies, however, have evaluated the role of melatonin on molecular mechanisms and clinical symptoms in PD. This review summarizes what is known regarding the impact of melatonin on PD in preclinical and clinical studies.
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Affiliation(s)
- Omid Reza Tamtaji
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran
| | - Russel J Reiter
- Department of Cellular and Structural Biology, UT Health San Antonio, San Antonio, TX, USA
| | - Reza Alipoor
- Student Research Committee, Hormozgan University of Medical Sciences, Bandar Abbas, Islamic Republic of Iran
| | | | - Ebrahim Kouchaki
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran.
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Espino J, Rodríguez AB, Pariente JA. Melatonin and Oxidative Stress in the Diabetic State: Clinical Implications and Potential Therapeutic Applications. Curr Med Chem 2019; 26:4178-4190. [PMID: 29637854 DOI: 10.2174/0929867325666180410094149] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Revised: 12/07/2017] [Accepted: 12/07/2017] [Indexed: 02/07/2023]
Abstract
All living organisms exhibit circadian rhythms, which govern the majority of biological functions, including metabolic processes. Misalignment of these circadian rhythms increases the risk of developing metabolic diseases. Thus, disruption of the circadian system has been proven to affect the onset of type 2 diabetes mellitus (T2DM). In this context, the pineal indoleamine melatonin is a signaling molecule able to entrain circadian rhythms. There is mounting evidence that suggests a link between disturbances in melatonin production and impaired insulin, glucose, lipid metabolism, and antioxidant capacity. Besides, several genetic association studies have causally associated various single nucleotide polymorphysms (SNPs) of the human MT2 receptor with increased risk of developing T2DM. Taken together, these data suggest that endogenous as well as exogenous melatonin may influence diabetes and associated metabolic disturbances not only by regulating insulin secretion but also by providing protection against reactive oxygen species (ROS) since pancreatic β-cells are very susceptible to oxidative stress due to their low antioxidant capacity.
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Affiliation(s)
- Javier Espino
- Department of Physiology (Neuroimmunophysiology and Chrononutrition Research Group), Faculty of Science, University of Extremadura, Badajoz, Spain
| | - Ana B Rodríguez
- Department of Physiology (Neuroimmunophysiology and Chrononutrition Research Group), Faculty of Science, University of Extremadura, Badajoz, Spain
| | - José A Pariente
- Department of Physiology (Neuroimmunophysiology and Chrononutrition Research Group), Faculty of Science, University of Extremadura, Badajoz, Spain
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Ghaderi A, Banafshe HR, Mirhosseini N, Motmaen M, Mehrzad F, Bahmani F, Aghadavod E, Mansournia MA, Reiter RJ, Karimi MA, Asemi Z. The effects of melatonin supplementation on mental health, metabolic and genetic profiles in patients under methadone maintenance treatment. Addict Biol 2019; 24:754-764. [PMID: 29949232 DOI: 10.1111/adb.12650] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Revised: 04/24/2018] [Accepted: 05/21/2018] [Indexed: 12/11/2022]
Abstract
This investigation was designed to determine the effect of melatonin supplementation on mental health parameters, metabolic and genetic profiles in patients under methadone maintenance treatment (MMT). This randomized, double-blind, placebo-controlled, clinical trial was conducted among 54 patients under MMT. Participants were randomly allocated to receive either 10 mg melatonin (2 melatonin capsules, 5 mg each) (n = 26) or placebo (n = 28) once a day, 1 hour before bedtime for 12 weeks. Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (β -4.08; 95 percent CI, -5.51, -2.65; P < 0.001), Beck Depression Inventory index (β -5.46; 95% CI, -8.92, -2.00; P = 0.003) and Beck Anxiety Inventory index (β -3.87; 95% CI, -5.96, -1.77; P = 0.001) and significantly increased International Index of Erectile Functions (β 5.59; 95% CI, 1.76, 9.42; P = 0.005) compared with the placebo. Subjects who received melatonin supplements had significantly lower serum insulin levels (β -2.53; 95% CI, -4.48, -0.59; P = 0.01), homeostasis model of assessment-insulin resistance (β -0.56; 95% CI, -1.03, -0.09; P = 0.01) and higher quantitative insulin sensitivity check index (β 0.01; 95% CI, 0.004, 0.02; P = 0.009) and HDL-cholesterol levels (β 3.71; 95% CI, 1.77, 5.64; P = 0.002) compared to placebo. Additionally, melatonin intake resulted in a significant reduction in serum high sensitivity C-reactive protein (β -0.15; 95% CI, -0.27, -0.02; P = 0.02), malondialdehyde (β -0.31; 95% CI, -0.57, -0.05; P = 0.02) and protein carbonyl (β -0.06; 95% CI, -0.09, -0.04; P < 0.001). This trial indicated that taking melatonin supplements for 12 weeks by patients under MMT had beneficial effects on their mental health metabolic profiles.
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Affiliation(s)
- Amir Ghaderi
- Department of Addiction Studies, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Hamid Reza Banafshe
- Department of Addiction Studies, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
- Department of Pharmacology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | | | - Maryam Motmaen
- Department of Psychiatry, School of Medicine, Kashan University of Medical Science, Kashan, Iran
| | - Fatemeh Mehrzad
- Department of Psychiatry, School of Medicine, Kashan University of Medical Science, Kashan, Iran
| | - Fereshteh Bahmani
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Esmat Aghadavod
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Mohammad Ali Mansournia
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Russel J Reiter
- Department of Cellular and Structural Biology, University of Texas Health Science, Center, San Antonio, TX, USA
| | - Mohammad-Amin Karimi
- Department of Educational Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
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Balmik AA, Chinnathambi S. Multi-Faceted Role of Melatonin in Neuroprotection and Amelioration of Tau Aggregates in Alzheimer's Disease. J Alzheimers Dis 2019; 62:1481-1493. [PMID: 29562506 DOI: 10.3233/jad-170900] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Alzheimer's disease (AD) is one of the major age related neurodegenerative diseases whose pathology arises due to the presence of two distinct protein aggregates, viz., amyloid-β plaques in extracellular matrix and tau neurofibrillary tangles in neurons. Multiple factors play a role in AD pathology, which includes familial mutations, oxidative stress, and post-translational modifications. Melatonin is an endocrine hormone, secreted during darkness, derived from tryptophan, and produced mainly by the pineal gland. It is an amphipathic molecule, which makes it suitable to cross not only blood-brain barrier, but also to enter several other subcellular compartments like mitochondria and endoplasmic reticulum. In this context, the neuroprotective effect of melatonin may be attributed to its role as an antioxidant. Melatonin's pleiotropic function as an antioxidant and neuroprotective agent has been widely studied. However, its direct effect on the aggregation of tau and amyloid-β needs to be explored. Furthermore, an important aspect of its function is its ability to regulate the process of phosphorylation of tau by affecting the function of kinases and phosphatases. In this review, we are focusing on the pleiotropic function of melatonin on the aspect of its neuroprotective function in tau pathology, which includes antioxidant function, regulation of enzymes, including kinases and enzymes involved in free radical scavenging and mitochondrial protection.
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Affiliation(s)
- Abhishek Ankur Balmik
- Neurobiology Group, Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune, India.,Academy of Scientific and Innovative Research (AcSIR), New Delhi, India
| | - Subashchandrabose Chinnathambi
- Neurobiology Group, Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune, India.,Academy of Scientific and Innovative Research (AcSIR), New Delhi, India
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Shen LL, Jin Y. Effects of MTNR1B genetic variants on the risk of type 2 diabetes mellitus: A meta-analysis. Mol Genet Genomic Med 2019; 7:e611. [PMID: 30811895 PMCID: PMC6503061 DOI: 10.1002/mgg3.611] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 01/25/2019] [Accepted: 02/05/2019] [Indexed: 12/17/2022] Open
Abstract
Background Whether melatonin receptor 1B (MTNR1B) variants are associated with type 2 diabetes mellitus (T2DM) remains unclear. Therefore, we performed this meta‐analysis to better explore correlations between MTNR1B variants and T2DM. Methods Literature research was performed in PubMed, Medline, and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results Totally 21 studies were enrolled to analyses. Pooled overall analyses showed that MTNR1B rs10830963 variant was significantly correlated with the susceptibility to T2DM (allele model: p = 0.02, OR = 0.97, 95% CI 0.95–1.00). Further subgroup analyses by ethnicity of participants revealed that rs10830963 variant was significantly correlated with the susceptibility to T2DM in South Asians, but not in Caucasians or East Asians. No any other positive results were found in overall and subgroup analyses. Conclusions Our findings indicated that MTNR1B rs10830963 variant might serve as a genetic biomarker of T2DM, especially in South Asians.
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Affiliation(s)
- Ling-Long Shen
- Department of Clinical Laboratory, Huzhou Maternity and Child Health Care Hospital, Huzhou, China
| | - Yin Jin
- Department of Clinical Laboratory, Huzhou Central Hospital, Huzhou, China
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Balakrishnan BB, Krishnasamy K, Mayakrishnan V, Selvaraj A. Moringa concanensis Nimmo extracts ameliorates hyperglycemia-mediated oxidative stress and upregulates PPARγ and GLUT4 gene expression in liver and pancreas of streptozotocin-nicotinamide induced diabetic rats. Biomed Pharmacother 2019; 112:108688. [PMID: 30798121 DOI: 10.1016/j.biopha.2019.108688] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Revised: 02/12/2019] [Accepted: 02/14/2019] [Indexed: 12/21/2022] Open
Abstract
The current study investigates the effects of ethanolic extract of M. concanensis Nimmo leaves (EEMCNL) with respect to its potent protective tissue damage, antioxidant properties in serum, liver and kidney, histopathological evaluation, and PPARγ and GLUT4 gene expression in liver and pancreatic tissue of Streptozotocin-Nicotinamide (STZ-NA) induced diabetic rats. Animals were divided into five groups (n = 5): control; diabetic; diabetic + EEMCNL; control + EEMCNL; and diabetic + glibenclamide. After 45 days of treatment with EEMCNL, MDA levels were significantly decreased in the diabetic-induced group when compared with the STZ-induced diabetic group (P < 0.05). The activities of serum enzymes AST, ALT, ALP, ACP and LDH were significantly decreased in serum and kidney, and increased in liver tissues of the EEMCNL-treated group as compared with the STZ-NA induced diabetic group (P < 0.05). The levels of total protein, urea, creatinine and uric acid observed in the diabetic group returned to normal by administration of EEMCNL (250 mg/kg) as relative to the STZ-NA induced diabetic group (P < 0.05). Furthermore, EEMCNL upregulated PPARγ and GLUT4 expression in liver and pancreatic tissue of the STZ-NA induced diabetic group rats. Taken together, these findings contribute to a better understanding of the hepatoprotective and renoprotective potential of EEMCNL against oxidative stress in the diabetic state, which was evidenced by the capacity of EEMCNL to modulate the antioxidant defence and to decrease lipid peroxidation in these tissues.
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Affiliation(s)
- Brindha Banu Balakrishnan
- Department of Biochemistry and Bioinformatics, Dr. MGR Janaki College of Arts and Science for Women, Affiliated to University of Madras, Chennai, 600028, Tamil Nadu, India; Department of Biochemistry, Kongunadu Arts and Science College, Affiliated to Bharathiar University, Coimbatore 641029, Tamil Nadu, India.
| | - Kalaivani Krishnasamy
- Department of Biochemistry, Kongunadu Arts and Science College, Affiliated to Bharathiar University, Coimbatore 641029, Tamil Nadu, India
| | - Vijayakumar Mayakrishnan
- Department of Nutrition, Dairy Science Division, National Institute of Animal Science, Rural Development Administration, Chungcheongnam-do, Cheonan, 31000, Republic of Korea
| | - Arokiyaraj Selvaraj
- Department of Food Science and Biotechnology, Sejong University, Gwangjingu, Seoul, Republic of Korea
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Effects of melatonin supplementation on blood lipid concentrations: A systematic review and meta-analysis of randomized controlled trials. Clin Nutr 2018; 37:1943-1954. [DOI: 10.1016/j.clnu.2017.11.003] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Revised: 09/26/2017] [Accepted: 11/07/2017] [Indexed: 12/25/2022]
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Igwe SC, Brigo F. Does Melatonin and Melatonin Agonists Improve the Metabolic Side Effects of Atypical Antipsychotics?: A Systematic Review and Meta-analysis of Randomized Controlled Trials. CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE 2018; 16:235-245. [PMID: 30121990 PMCID: PMC6124875 DOI: 10.9758/cpn.2018.16.3.235] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Revised: 10/18/2017] [Accepted: 10/19/2017] [Indexed: 01/21/2023]
Abstract
Atypical antipsychotics (AAPs) are increasingly used for the treatment of psychotic disorders but are known to be associated with metabolic abnormalities. This study is a systematic review and meta-analysis of randomized controlled trials (RCTs) studying the effectiveness of melatonin for the amelioration of AAP-induced metabolic syndrome. The MEDLINE (accessed via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials, PsycINFO, LILACS, CINAHL, and OpenGrey databases were searched for RCTs without language restrictions. Inclusion criteria were randomized, double-blind clinical trials comparing melatonin or melatonin agonists with placebo for the amelioration of AAP-induced effects at any age with selected components of metabolic syndrome as outcome measures. Two reviewers independently selected articles and assessed quality using Cochrane risk of bias and concealment tools. Of 53 records, five RCTs were eligible for the systematic review and three for the meta-analysis. The meta-analyses showed no statistically significant difference in any anthropometric or metabolic variable considered. Analysis according to psychiatric diagnosis from one RCT showed significant decreases in diastolic blood pressure (5.5 vs. −5.7 mmHg for the placebo and melatonin groups, respectively; p=0.001), fat mass (2.7 vs. 0.2 kg, respectively; p=0.032), and triglycerides (D) (50.1 vs. −20 mg/dl, respectively; p=0.08) in the bipolar group but not the schizophrenia group. Although limited to five RCTs with small sample sizes, evidence from RCT indicates that melatonin improves AAP-induced metabolic syndrome. This beneficial effect seems more significant in patients with bipolar disorder than those with schizophrenia. Further RCTs are needed to definitively establish the potential ameliorative effect of melatonin and to justify its efficacy as an add-on therapy to curtail AAP-induced metabolic syndrome.
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Affiliation(s)
- Stanley C Igwe
- Department of Neuro-Psychiatry, Federal Teaching Hospital, Abakaliki, Nigeria
| | - Francesco Brigo
- Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy
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Onaolapo AY, Onaolapo OJ. Circadian dysrhythmia-linked diabetes mellitus: Examining melatonin’s roles in prophylaxis and management. World J Diabetes 2018; 9:99-114. [PMID: 30079146 PMCID: PMC6068738 DOI: 10.4239/wjd.v9.i7.99] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Revised: 06/01/2018] [Accepted: 06/08/2018] [Indexed: 02/05/2023] Open
Abstract
Diabetes mellitus is a chronic, life-threatening metabolic disorder that occurs worldwide. Despite an increase in the knowledge of the risk factors that are associated with diabetes mellitus, its worldwide prevalence has continued to rise; thus, necessitating more research into its aetiology. Recent researches are beginning to link a dysregulation of the circadian rhythm to impairment of intermediary metabolism; with evidences that circadian rhythm dysfunction might play an important role in the aetiology, course or prognosis of some cases of diabetes mellitus. These evidences thereby suggest possible relationships between the circadian rhythm regulator melatonin, and diabetes mellitus. In this review, we discuss the roles of the circadian rhythm in the regulation of the metabolism of carbohydrates and other macronutrients; with emphasis on the importance of melatonin and the impacts of its deficiency on carbohydrate homeostasis. Also, the possibility of using melatonin and its analogs for the “prophylaxis” or management of diabetes mellitus is also considered.
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Affiliation(s)
- Adejoke Y Onaolapo
- Behavioural Neuroscience/Neurobiology Unit, Department of Anatomy, Ladoke Akintola University of Technology, Ogbomosho 210211, Oyo State, Nigeria
| | - Olakunle J Onaolapo
- Behavioural Neuroscience/Neuropharmacology Unit, Department of Pharmacology, Ladoke Akintola University of Technology, Osogbo 230263, Osun State, Nigeria
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The effect of melatonin on lipid peroxide oxidation, oxidative modification of proteins and mitochondria swelling in the skeletal muscle tissue of rats under alloxan diabetes. UKRAINIAN BIOCHEMICAL JOURNAL 2018. [DOI: 10.15407/ubj90.03.062] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
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Kadry SM, El-Dakdoky MH, Haggag NZ, Rashed LA, Hassen MT. Melatonin improves the therapeutic role of mesenchymal stem cells in diabetic rats. Toxicol Mech Methods 2018; 28:529-538. [DOI: 10.1080/15376516.2018.1471634] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Affiliation(s)
- Shadia M. Kadry
- Department of Zoology, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo, Egypt
| | - Mai H. El-Dakdoky
- Department of Zoology, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo, Egypt
| | - Nawal Z. Haggag
- Department of Zoology, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo, Egypt
| | - Laila A. Rashed
- Department of Zoology, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo, Egypt
| | - Marwa T. Hassen
- Department of Zoology, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo, Egypt
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Agahi M, Akasheh N, Ahmadvand A, Akbari H, Izadpanah F. Effect of melatonin in reducing second-generation antipsychotic metabolic effects: A double blind controlled clinical trial. Diabetes Metab Syndr 2018; 12:9-15. [PMID: 28847468 DOI: 10.1016/j.dsx.2017.08.004] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Accepted: 08/07/2017] [Indexed: 12/15/2022]
Abstract
INTRODUCTION The use of second-generation atypical antipsychotics has an increasing role in the development of metabolic syndrome. However, these medications due to metabolic disorders can lead to an increased risk of cardiovascular disease and subsequently mortality as well as reduced adherence to treatment. The main objective of current study was to determine the ability of melatonin to reduce the metabolic effects of second-generation antipsychotics. METHODS This double blind controlled clinical trial was conducted on 100 patients aged 18-64 years old were treated with the second-generation antipsychotics for the first time. The patients were divided randomly into two groups of 50. The case group received slow-release melatonin at a dose of 3mg and the control group was given oral placebo at 8 p.m. RESULTS The findings in melatonin group indicated significantly increase of HDL and decreased fasting blood sugar and systolic blood pressure, as well as had statistically significant increase in waist circumference, weight and BMI compared with placebo group. CONCLUSION According to the findings, it can be claimed that the addition of melatonin to atypical antipsychotics has led to a reduction in some of the metabolic effects of these drugs. In this study, HDL level was increased, and the mean systolic blood pressure and FBS were decreased in the melatonin group. Considering that these factors are contributing to cardiovascular disease as a leading cause of mortality in psychiatric patients, so the use of melatonin can reduce some of the medical effects of long-term treatment of atypical antipsychotics.
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Affiliation(s)
- Mansour Agahi
- Department of Psychiatry, Kashan University of Medical Sciences, Kashan, Iran
| | - Negar Akasheh
- Department of Psychiatry, Kashan University of Medical Sciences, Kashan, Iran
| | - Afshin Ahmadvand
- Department of Psychiatry, Kashan University of Medical Sciences, Kashan, Iran
| | - Hossein Akbari
- Biostatictics Department, Kashan University of Medical Sciences, Kashan, Iran
| | - Fatemeh Izadpanah
- Department of Psychiatry, Kashan University of Medical Sciences, Kashan, Iran; Food and Drug Laboratory Research Center and Food and Drug Reference Control Laboratories Center, Food & Drug Administration of Iran, MOH & ME, Tehran, Iran.
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Sun H, Wang X, Chen J, Gusdon AM, Song K, Li L, Qu S. Melatonin Treatment Improves Insulin Resistance and Pigmentation in Obese Patients with Acanthosis Nigricans. Int J Endocrinol 2018; 2018:2304746. [PMID: 29706998 PMCID: PMC5867607 DOI: 10.1155/2018/2304746] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Revised: 12/21/2017] [Accepted: 01/10/2018] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVE This study aimed to determine the effects of melatonin on insulin resistance in obese patients with acanthosis nigricans (AN). METHODS A total of 17 obese patients with acanthosis nigricans were recruited in a 12-week pilot open trial. Insulin sensitivity, glucose metabolism, inflammatory factors, and other biochemical parameters before and after the administration of melatonin were measured. RESULTS After 12 weeks of treatment with melatonin (3 mg/day), homeostasis model assessment insulin resistance index (HOMA-IR) (8.99 ± 5.10 versus 7.77 ± 5.21, p < 0.05) and fasting insulin (37.09 5 ± 20.26 μU/ml versus 32.10 ± 20.29 μU/ml, p < 0.05) were significantly decreased. Matsuda index (2.82 ± 1.54 versus 3.74 ± 2.02, p < 0.05) was significantly increased. There were also statistically significant declines in the AN scores of the neck and axilla, body weight, body mass index, body fat, visceral index, neck circumference, waist circumference, and inflammatory markers. CONCLUSIONS It was concluded that melatonin could improve cutaneous symptoms in obese patients with acanthosis nigricans by improving insulin sensitivity and inflammatory status. This trial is registered with ClinicalTrials.gov NCT02604095.
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Affiliation(s)
- Hang Sun
- Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China
| | - Xingchun Wang
- Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China
| | - Jiaqi Chen
- Department of Endocrinology and Metabolism, SuZhou Municipal Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Aaron M. Gusdon
- Division of Neuropathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
- Department of Neurology, Weill Cornell Medical College, New York, NY 10065, USA
| | - Kexiu Song
- Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China
| | - Liang Li
- Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China
| | - Shen Qu
- Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China
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Cardinali DP, Vigo DE. Melatonin, mitochondria, and the metabolic syndrome. Cell Mol Life Sci 2017; 74:3941-3954. [PMID: 28819865 PMCID: PMC11107716 DOI: 10.1007/s00018-017-2611-0] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 08/03/2017] [Indexed: 12/12/2022]
Abstract
A number of risk factors for cardiovascular disease including hyperinsulinemia, glucose intolerance, dyslipidemia, obesity, and elevated blood pressure are collectively known as metabolic syndrome (MS). Since mitochondrial activity is modulated by the availability of energy in cells, the disruption of key regulators of metabolism in MS not only affects the activity of mitochondria but also their dynamics and turnover. Therefore, a link of MS with mitochondrial dysfunction has been suspected since long. As a chronobiotic/cytoprotective agent, melatonin has a special place in prevention and treatment of MS. Melatonin levels are reduced in diseases associated with insulin resistance like MS. Melatonin improves sleep efficiency and has antioxidant and anti-inflammatory properties, partly for its role as a metabolic regulator and mitochondrial protector. We discuss in the present review the several cytoprotective melatonin actions that attenuate inflammatory responses in MS. The clinical data that support the potential therapeutical value of melatonin in human MS are reviewed.
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Affiliation(s)
- Daniel P Cardinali
- BIOMED-UCA-CONICET and Department of Teaching and Research, Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, Av. Alicia Moreau de Justo 1500, 4o piso, 1107, Buenos Aires, Argentina.
| | - Daniel E Vigo
- BIOMED-UCA-CONICET and Department of Teaching and Research, Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, Av. Alicia Moreau de Justo 1500, 4o piso, 1107, Buenos Aires, Argentina
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Melatonin Decreases Glucose Metabolism in Prostate Cancer Cells: A 13C Stable Isotope-Resolved Metabolomic Study. Int J Mol Sci 2017; 18:ijms18081620. [PMID: 28933733 PMCID: PMC5578012 DOI: 10.3390/ijms18081620] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2017] [Revised: 07/18/2017] [Accepted: 07/20/2017] [Indexed: 12/18/2022] Open
Abstract
The pineal neuroindole melatonin exerts an exceptional variety of systemic functions. Some of them are exerted through its specific membrane receptors type 1 and type 2 (MT1 and MT2) while others are mediated by receptor-independent mechanisms. A potential transport of melatonin through facilitative glucose transporters (GLUT/SLC2A) was proposed in prostate cancer cells. The prostate cells have a particular metabolism that changes during tumor progression. During the first steps of carcinogenesis, oxidative phosphorylation is reactivated while the switch to the “Warburg effect” only occurs in advanced tumors and in the metastatic stage. Here, we investigated whether melatonin might change prostate cancer cell metabolism. To do so, 13C stable isotope-resolved metabolomics in androgen sensitive LNCaP and insensitive PC-3 prostate cancer cells were employed. In addition to metabolite 13C-labeling, ATP/AMP levels, and lactate dehydrogenase or pentose phosphate pathway activity were measured. Melatonin reduces lactate labeling in androgen-sensitive cells and it also lowers 13C-labeling of tricarboxylic acid cycle metabolites and ATP production. In addition, melatonin reduces lactate 13C-labeling in androgen insensitive prostate cancer cells. Results demonstrated that melatonin limits glycolysis as well as the tricarboxylic acid cycle and pentose phosphate pathway in prostate cancer cells, suggesting that the reduction of glucose uptake is a major target of the indole in this tumor type.
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Machado-Vieira R, Henter ID, Zarate CA. New targets for rapid antidepressant action. Prog Neurobiol 2017; 152:21-37. [PMID: 26724279 PMCID: PMC4919246 DOI: 10.1016/j.pneurobio.2015.12.001] [Citation(s) in RCA: 110] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Revised: 11/30/2015] [Accepted: 12/07/2015] [Indexed: 02/08/2023]
Abstract
Current therapeutic options for major depressive disorder (MDD) and bipolar disorder (BD) are associated with a lag of onset that can prolong distress and impairment for patients, and their antidepressant efficacy is often limited. All currently approved antidepressant medications for MDD act primarily through monoaminergic mechanisms. Glutamate is the major excitatory neurotransmitter in the central nervous system, and glutamate and its cognate receptors are implicated in the pathophysiology of MDD, and in the development of novel therapeutics for this disorder. The rapid and robust antidepressant effects of the N-methyl-d-aspartate (NMDA) antagonist ketamine were first observed in 2000. Since then, other NMDA receptor antagonists have been studied in MDD. Most have demonstrated relatively modest antidepressant effects compared to ketamine, but some have shown more favorable characteristics. This article reviews the clinical evidence supporting the use of novel glutamate receptor modulators with direct affinity for cognate receptors: (1) non-competitive NMDA receptor antagonists (ketamine, memantine, dextromethorphan, AZD6765); (2) subunit (GluN2B)-specific NMDA receptor antagonists (CP-101,606/traxoprodil, MK-0657); (3) NMDA receptor glycine-site partial agonists (GLYX-13); and (4) metabotropic glutamate receptor (mGluR) modulators (AZD2066, RO4917523/basimglurant). We also briefly discuss several other theoretical glutamate receptor targets with preclinical antidepressant-like efficacy that have yet to be studied clinically; these include α-amino-3-hydroxyl-5-methyl-4-isoxazoleproprionic acid (AMPA) agonists and mGluR2/3 negative allosteric modulators. The review also discusses other promising, non-glutamatergic targets for potential rapid antidepressant effects, including the cholinergic system (scopolamine), the opioid system (ALKS-5461), corticotropin releasing factor (CRF) receptor antagonists (CP-316,311), and others.
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Affiliation(s)
- Rodrigo Machado-Vieira
- Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
| | - Ioline D Henter
- Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
| | - Carlos A Zarate
- Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
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Meng X, Li Y, Li S, Zhou Y, Gan RY, Xu DP, Li HB. Dietary Sources and Bioactivities of Melatonin. Nutrients 2017; 9:E367. [PMID: 28387721 PMCID: PMC5409706 DOI: 10.3390/nu9040367] [Citation(s) in RCA: 204] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2017] [Revised: 03/14/2017] [Accepted: 03/31/2017] [Indexed: 12/14/2022] Open
Abstract
Insomnia is a serious worldwide health threat, affecting nearly one third of the general population. Melatonin has been reported to improve sleep efficiency and it was found that eating melatonin-rich foods could assist sleep. During the last decades, melatonin has been widely identified and qualified in various foods from fungi to animals and plants. Eggs and fish are higher melatonin-containing food groups in animal foods, whereas in plant foods, nuts are with the highest content of melatonin. Some kinds of mushrooms, cereals and germinated legumes or seeds are also good dietary sources of melatonin. It has been proved that the melatonin concentration in human serum could significantly increase after the consumption of melatonin containing food. Furthermore, studies show that melatonin exhibits many bioactivities, such as antioxidant activity, anti-inflammatory characteristics, boosting immunity, anticancer activity, cardiovascular protection, anti-diabetic, anti-obese, neuroprotective and anti-aging activity. This review summaries the dietary sources and bioactivities of melatonin, with special attention paid to the mechanisms of action.
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Affiliation(s)
- Xiao Meng
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
| | - Ya Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
| | - Sha Li
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China.
| | - Yue Zhou
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
| | - Ren-You Gan
- School of Biological Sciences, The University of Hong Kong, Hong Kong 999077, China.
| | - Dong-Ping Xu
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
| | - Hua-Bin Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
- South China Sea Bioresource Exploitation and Utilization Collaborative Innovation Center, Sun Yat-sen University, Guangzhou 510006, China.
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Ibrahim DS. Neuroprotective effect of Cucumis melo Var. flexuosus leaf extract on the brains of rats with streptozotocin-induced diabetes. Metab Brain Dis 2017; 32:69-75. [PMID: 27488111 DOI: 10.1007/s11011-016-9886-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2015] [Accepted: 07/28/2016] [Indexed: 11/26/2022]
Abstract
The central nervous system is one of the most vulnerable organs affected by the oxidative stress associated with diabetes mellitus. Healthy food provides an important source for antioxidants. Therefore, the protective effect of Cucumis melo var. flexuosus (C. melo var. flexuosus) leaf extract on the brains of diabetic rats was investigated. Adult male albino rats divided into 5 groups of 6 rats each were assigned into a normal control group and four diabetic groups. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg bw). One of the four diabetic groups was left untreated and was considered as a diabetic control group while the three other groups were treated with C. melo var. flexuosus leaf extract at the doses of 30, 60 and 120 mg/kg bw for a period of 30 days. After completion of experimental duration plasma and brains were used for evaluating biochemical changes. The obtained data showed that C. melo var. flexuosus leaf extract treatment lowered blood glucose, glycated hemoglobin, brain tumor necrosis factor-alpha, interleukin levels, brain malondialdehyde content and caspase-3 activity. Furthermore, the treatment resulted in a marked increase in plasma dopamine, melatonin, brain vascular endothelial growth factor-A levels, brain catalase and superoxide dismutase activities. From the present study, it can be concluded that the C. melo var. flexuosus leaf extract exerts a neuroprotective effect against oxidative damage associated with diabetes.
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Affiliation(s)
- Doaa S Ibrahim
- Department of Zoology, Faculty of Science, Benha University, Banha, Egypt.
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Hardeland R. Melatonin and the pathologies of weakened or dysregulated circadian oscillators. J Pineal Res 2017; 62. [PMID: 27763686 DOI: 10.1111/jpi.12377] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Accepted: 10/18/2016] [Indexed: 12/20/2022]
Abstract
Dynamic aspects of melatonin's actions merit increasing future attention. This concerns particularly entirely different effects in senescent, weakened oscillators and in dysregulated oscillators of cancer cells that may be epigenetically blocked. This is especially obvious in the case of sirtuin 1, which is upregulated by melatonin in aged tissues, but strongly downregulated in several cancer cells. These findings are not at all controversial, but are explained on the basis of divergent changes in weakened and dysregulated oscillators. Similar findings can be expected to occur in other accessory oscillator components that are modulated by melatonin, among them several transcription factors and metabolic sensors. Another cause of opposite effects concerns differences between nocturnally active laboratory rodents and the diurnally active human. This should be more thoroughly considered in the field of metabolic syndrome and related pathologies, especially with regard to type 2 diabetes and other aspects of insulin resistance. Melatonin was reported to impair glucose tolerance in humans, especially in carriers of the risk allele of the MT2 receptor gene, MTNR1B, that contains the SNP rs10830963. These findings contrast with numerous reports on improvements of glucose tolerance in preclinical studies. However, the relationship between melatonin and insulin may be more complex, as indicated by loss-of-function mutants of the MT2 receptor that are also prodiabetic, by the age-dependent time course of risk allele overexpression, by progressive reduction in circadian amplitudes and melatonin secretion, which are aggravated in diabetes. By supporting high-amplitude rhythms, melatonin may be beneficial in preventing or delaying diabetes.
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Affiliation(s)
- Rüdiger Hardeland
- Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Göttingen, Göttingen, Germany
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Sun H, Wang X, Chen J, Song K, Gusdon AM, Li L, Bu L, Qu S. Melatonin improves non-alcoholic fatty liver disease via MAPK-JNK/P38 signaling in high-fat-diet-induced obese mice. Lipids Health Dis 2016; 15:202. [PMID: 27876064 PMCID: PMC5120511 DOI: 10.1186/s12944-016-0370-9] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2016] [Accepted: 11/10/2016] [Indexed: 01/21/2023] Open
Abstract
Background Melatonin can regulate lipid metabolism, increase insulin sensitivity, regulate glucose metabolism and reduce body weight. This study is aimed to determine the effects and mechanism of action of melatonin on non-alcoholic fatty liver disease (NAFLD) in high-fat-diet (HFD) induced obese mice. Methods NAFLD was induced by HFD in C57BL/6 mice. A total of 24 mice were randomly assigned to 4 groups. Groups A and B were fed with HFD for 36 weeks while groups C and D were fed with a regular diet (RD). During the last 12 weeks, Groups A and C were treated with 10 mg/kg melatonin while Groups B and D were treated with water in the same volume by intragastric administration. Body and liver weight, blood glucose, serum transaminases and lipid levels, and markers of hepatic inflammation were measured. Histological analyses were also performed on liver tissue. Results After 12 weeks of treatment with melatonin, body weights (Group A: before 53.11 ± 0.72 vs after 12w treatment 39.48 ± 0.74) and liver weights (A 1.93 ± 0.09 g vs B 2.92 ± 0.19 g vs C 1.48 ± 0.09 g vs D 1.49 ± 0.10 g), fasting plasma glucose, alanine transaminase (A 24.33 ± 11.90 IU/L vs B 60.80 ± 10.18 IU/L vs C 13.01 ± 3.49 IU/L vs D 16.62 ± 2.00 IU/L), and low-density cholesterol (A 0.24 ± 0.06 mmol/L vs B 1.57 ± 0.10 mmol/L vs C 0.28 ± 0.06 mmol/L vs D 0.29 ± 0.03 mmol/L) were significantly decreased in HFD mice. HFD fed mice treated with melatonin showed significantly less liver steatosis. Treatment of HFD fed mice with melatonin led to a significant decrease in the expression of TNF-α, IL-1β, and IL-6 measured using quantitative real-time polymerase chain reaction (qRT-PCR). HFD fed mice demonstrated increased phosphorylation of P38 and JNK1/2, which was reduced by melatonin treatment. Conclusions The study concluded that melatonin could improve NAFLD by decreasing body weight and reduce inflammation in HFD induced obese mice by modulating the MAPK-JNK/P38 signaling pathway.
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Affiliation(s)
- Hang Sun
- Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China
| | - Xingchun Wang
- Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China
| | - Jiaqi Chen
- Nanjing Medical University, Nanjing, Jiangsu, 210029, China
| | - Kexiu Song
- Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China
| | - Aaron M Gusdon
- Department of Neurology, Weill Cornell Medical College, New York, NY, 10065, USA
| | - Liang Li
- Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China
| | - Le Bu
- Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China
| | - Shen Qu
- Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
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Colares JR, Schemitt EG, Hartmann RM, Licks F, Soares MDC, Bosco AD, Marroni NP. Antioxidant and anti-inflammatory action of melatonin in an experimental model of secondary biliary cirrhosis induced by bile duct ligation. World J Gastroenterol 2016; 22:8918-8928. [PMID: 27833383 PMCID: PMC5083797 DOI: 10.3748/wjg.v22.i40.8918] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Revised: 08/24/2016] [Accepted: 09/14/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the effects of melatonin (Mel) on oxidative stress in an experimental model of bile duct ligation (BDL). METHODS Male Wistar rats (n = 32, weight ± 300 g) were allocated across four groups: CO (sham BDL), BDL (BDL surgery), CO + Mel (sham BDL and Mel administration) and BDL + Mel (BDL surgery and Mel administration). Mel was administered intraperitoneally for 2 wk, starting on postoperative day 15, at a dose of 20 mg/kg. RESULTS Mel was effective at the different standards, reestablishing normal liver enzyme levels, reducing the hepatosomatic and splenosomatic indices, restoring lipoperoxidation and antioxidant enzyme concentrations, reducing fibrosis and inflammation, and thereby reducing liver tissue injury in the treated animals. CONCLUSION The results of this study suggest a protective effect of Mel when administered to rats with secondary biliary cirrhosis induced by BDL.
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Georgiev T, Tolekova A, Kalfin R, Hadzhibozheva P. Short-term administration of melatonin or ghrelin on diabetic rats: effects on angiotensin II and vasopressin-induced uterine contractility. Physiol Res 2016; 66:125-133. [PMID: 27782742 DOI: 10.33549/physiolres.933337] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
The aim of the present study was to investigate the effects of Angiotensin II (Ang II) and Arginin-Vasopressin (AVP) on contractility of non-pregnant uterus in diabetic Wistar rats and to explore whether one-week administration of Melatonin (MLT) or Ghrelin (GHR) will change the response of diabetic uterine muscle to AngII and AVP. Uterine horns, prepared by the method of isolated tissues were investigated as well as glycemic profile, blood pressure and body weight. The research of smooth muscle contractions was made by a new method of analysis, characterizing in detail the various phases of the myometrial activity. Differences in the development of the peptide-mediated smooth muscle contractions depending on the phase of the estrous cycle were observed. Experimental diabetes had a pronounced negative effect on force and time-parameters of AngII and AVP-stimulated uterine contractions. Administration of GHR or MLT had a beneficial effect on the glycemic status of diabetic rats and partially improved the response of uterine preparations to the peptides. The application of MLT increased both force and time-parameters of Ang II-and AVP-stimulated uterine contractions while treatment with GHR increased power characteristics and shortened contraction and relaxation of the smooth muscle process.
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Affiliation(s)
- T Georgiev
- Department of Physiology, Pathophysiology and Pharmacology, Medical Faculty, Trakia University, Stara Zagora, Bulgaria.
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Gonçalves AL, Martini Ferreira A, Ribeiro RT, Zukerman E, Cipolla-Neto J, Peres MFP. Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention. J Neurol Neurosurg Psychiatry 2016; 87:1127-32. [PMID: 27165014 PMCID: PMC5036209 DOI: 10.1136/jnnp-2016-313458] [Citation(s) in RCA: 105] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Accepted: 04/21/2016] [Indexed: 01/03/2023]
Abstract
INTRODUCTION Melatonin has been studied in headache disorders. Amitriptyline is efficacious for migraine prevention, but its unfavourable side effect profile limits its use. METHODS A randomised, double-blind, placebo-controlled study was carried out. Men and women, aged 18-65 years, with migraine with or without aura, experiencing 2-8 attacks per month, were enrolled. After a 4-week baseline phase, 196 participants were randomised to placebo, amitriptyline 25 mg or melatonin 3 mg, and 178 took a study medication and were followed for 3 months (12 weeks). The primary outcome was the number of migraine headache days per month at baseline versus last month. Secondary end points were responder rate, migraine intensity, duration and analgesic use. Tolerability was also compared between groups. RESULTS Mean headache frequency reduction was 2.7 migraine headache days in the melatonin group, 2.2 for amitriptyline and 1.1 for placebo. Melatonin significantly reduced headache frequency compared with placebo (p=0.009), but not to amitriptyline (p=0.19). Melatonin was superior to amitriptyline in the percentage of patients with a greater than 50% reduction in migraine frequency. Melatonin was better tolerated than amitriptyline. Weight loss was found in the melatonin group, a slight weight gain in placebo and significantly for amitriptyline users. CONCLUSIONS Melatonin 3 mg is better than placebo for migraine prevention, more tolerable than amitriptyline and as effective as amitriptyline 25 mg.
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Affiliation(s)
- Andre Leite Gonçalves
- Albert Einstein Hospital, São Paulo, Brazil Department of Neurology, UNIFESP, São Paulo, Brazil
| | | | - Reinaldo Teixeira Ribeiro
- Department of Neurology, UNIFESP, São Paulo, Brazil Neurology Department, FMABC, Santo Andre, Brazil
| | | | - José Cipolla-Neto
- Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil
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