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      The role of dietary antioxidants in type 2 diabetes and neurodegenerative disorders: An assessment of the benefit profile

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          Abstract

          Healthy diet is vital to cellular health. The human body succumbs to numerous diseases which afflict severe economic and psychological burdens on the patient and family. Oxidative stress is a possible crucial regulator of various pathologies, including type 2 diabetes and neurodegenerative diseases. It generates reactive oxygen species (ROS) that trigger the dysregulation of essential cellular functions, ultimately affecting cellular health and homeostasis. However, lower levels of ROS can be advantageous and are implicated in a variety of signaling pathways. Due to this dichotomy, the terms oxidative “eustress,” which refers to a good oxidative event, and “distress,” which can be hazardous, have developed. ROS affects multiple signaling pathways, leading to compromised insulin secretion, insulin resistance, and β-cell dysfunction in diabetes. ROS is also associated with increased mitochondrial dysfunction and neuroinflammation, aggravating neurodegenerative conditions in the body, particularly with age. Treatment includes drugs/therapies often associated with dependence, side effects including non-selectivity, and possible toxicity, particularly in the long run. It is imperative to explore alternative medicines as an adjunct therapy, utilizing natural remedies/resources to avoid all the possible harms. Antioxidants are vital components of our body that fight disease by reducing oxidative stress or nullifying the excess toxic free radicals produced under various pathological conditions. In this review, we focus on the antioxidant effects of components of dietary foods such as tea, coffee, wine, oils, and honey and the role and mechanism of action of these antioxidants in alleviating type 2 diabetes and neurodegenerative disorders. We aim to provide information about possible alternatives to drug treatments used alone or combined to reduce drug intake and encourage the consumption of natural ingredients at doses adequate to promote health and combat pathologies while reducing unwanted risks and side effects.

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          Most cited references217

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          Reactive oxygen species (ROS) as pleiotropic physiological signalling agents

          'Reactive oxygen species' (ROS) is an umbrella term for an array of derivatives of molecular oxygen that occur as a normal attribute of aerobic life. Elevated formation of the different ROS leads to molecular damage, denoted as 'oxidative distress'. Here we focus on ROS at physiological levels and their central role in redox signalling via different post-translational modifications, denoted as 'oxidative eustress'. Two species, hydrogen peroxide (H2O2) and the superoxide anion radical (O2·-), are key redox signalling agents generated under the control of growth factors and cytokines by more than 40 enzymes, prominently including NADPH oxidases and the mitochondrial electron transport chain. At the low physiological levels in the nanomolar range, H2O2 is the major agent signalling through specific protein targets, which engage in metabolic regulation and stress responses to support cellular adaptation to a changing environment and stress. In addition, several other reactive species are involved in redox signalling, for instance nitric oxide, hydrogen sulfide and oxidized lipids. Recent methodological advances permit the assessment of molecular interactions of specific ROS molecules with specific targets in redox signalling pathways. Accordingly, major advances have occurred in understanding the role of these oxidants in physiology and disease, including the nervous, cardiovascular and immune systems, skeletal muscle and metabolic regulation as well as ageing and cancer. In the past, unspecific elimination of ROS by use of low molecular mass antioxidant compounds was not successful in counteracting disease initiation and progression in clinical trials. However, controlling specific ROS-mediated signalling pathways by selective targeting offers a perspective for a future of more refined redox medicine. This includes enzymatic defence systems such as those controlled by the stress-response transcription factors NRF2 and nuclear factor-κB, the role of trace elements such as selenium, the use of redox drugs and the modulation of environmental factors collectively known as the exposome (for example, nutrition, lifestyle and irradiation).
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            Oxidative Stress

            Oxidative stress is two sided: Whereas excessive oxidant challenge causes damage to biomolecules, maintenance of a physiological level of oxidant challenge, termed oxidative eustress, is essential for governing life processes through redox signaling. Recent interest has focused on the intricate ways by which redox signaling integrates these converse properties. Redox balance is maintained by prevention, interception, and repair, and concomitantly the regulatory potential of molecular thiol-driven master switches such as Nrf2/Keap1 or NF-κB/IκB is used for system-wide oxidative stress response. Nonradical species such as hydrogen peroxide (H2O2) or singlet molecular oxygen, rather than free-radical species, perform major second messenger functions. Chemokine-controlled NADPH oxidases and metabolically controlled mitochondrial sources of H2O2 as well as glutathione- and thioredoxin-related pathways, with powerful enzymatic back-up systems, are responsible for fine-tuning physiological redox signaling. This makes for a rich research field spanning from biochemistry and cell biology into nutritional sciences, environmental medicine, and molecular knowledge-based redox medicine.
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              The KEAP1-NRF2 System: a Thiol-Based Sensor-Effector Apparatus for Maintaining Redox Homeostasis.

              The Kelch-like ECH-associated protein 1-NF-E2-related factor 2 (KEAP1-NRF2) system forms the major node of cellular and organismal defense against oxidative and electrophilic stresses of both exogenous and endogenous origins. KEAP1 acts as a cysteine thiol-rich sensor of redox insults, whereas NRF2 is a transcription factor that robustly transduces chemical signals to regulate a battery of cytoprotective genes. KEAP1 represses NRF2 activity under quiescent conditions, whereas NRF2 is liberated from KEAP1-mediated repression on exposure to stresses. The rapid inducibility of a response based on a derepression mechanism is an important feature of the KEAP1-NRF2 system. Recent studies have unveiled the complexities of the functional contributions of the KEAP1-NRF2 system and defined its broader involvement in biological processes, including cell proliferation and differentiation, as well as cytoprotection. In this review, we describe historical milestones in the initial characterization of the KEAP1-NRF2 system and provide a comprehensive overview of the molecular mechanisms governing the functions of KEAP1 and NRF2, as well as their roles in physiology and pathology. We also refer to the clinical significance of the KEAP1-NRF2 system as an important prophylactic and therapeutic target for various diseases, particularly aging-related disorders. We believe that controlled harnessing of the KEAP1-NRF2 system is a key to healthy aging and well-being in humans.
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                Author and article information

                Contributors
                Journal
                Heliyon
                Heliyon
                Heliyon
                Elsevier
                2405-8440
                30 December 2022
                January 2023
                30 December 2022
                : 9
                : 1
                : e12698
                Affiliations
                [a ]Department of Human Genetics-Precision Medicine in Diabetes Prevention Program, Sidra Medicine, P.O. Box 26999, Doha, Qatar
                [b ]College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, P.O. Box 34110, Doha, Qatar
                [c ]Department of Genetic Medicine, Weill Cornell Medical College, Doha, P.O. Box 24144, Doha, Qatar
                [d ]Department of Human Genetics, Laboratory of Genomic Medicine-Precision Medicine Program, Sidra Medicine, P.O. Box 26999, Doha, Qatar
                Author notes
                []Corresponding author. aakil@ 123456sidra.org
                Article
                S2405-8440(22)03986-X e12698
                10.1016/j.heliyon.2022.e12698
                9826852
                36632095
                d424acd0-631c-420b-9667-654f0db7fb23
                © 2023 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 11 August 2022
                : 29 November 2022
                : 26 December 2022
                Categories
                Review Article

                antioxidants,type 2 diabetes,neurodegenerative diseases,reactive oxygen species,diet,therapeutics

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