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Antioxidant Enzymes and Human Health

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  • JSS College of Pharmacy-Ooty (JSS Academy of Higher Education & Research-Mysuru)
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... N-Ribosylnicotinamide: quinone oxidoreductase 2 (NQO2) catalyses the reduction of quinones using reduced N-ribosylnicotinamide (NRH) or its derivatives as co-substrates to generate hydroquinones and reactive oxygen species (ROS) [1][2][3]. The excessive ROS production has deleterious effects on various cells and body organs. ...
... ROS can react with proteins, lipids, and DNA base pairs, leading to protein denaturation, lipid peroxidation, loss in enzymatic function, and formation of DNA adducts. Consequently, ROS can lead to tissue destruction and oxidative stress, which are correlated with several health disorders, including diabetes, stroke, heart attacks, atherosclerosis, and neurodegenerative diseases [1]. ...
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Citation: Belgath, A.A.; Emam, A.M.; Taujanskas, J.; Bryce, R.A.; Freeman, S.; Stratford, I.J. Discovery of Potent Benzothiazole Inhibitors of Oxidoreductase NQO2, a Target for Inflammation and Cancer. Int. J. Mol. Sci. 2024, 25, 12025. https://doi. Abstract: Inhibitors of NQO2 (NRH: quinone oxidoreductase) have potential application in several areas of medicine and pharmacology, including cancer, neurodegeneration (PD and AD), stroke, and diabetes. Here, resveratrol, a known inhibitor of NQO2, was used as the lead by replacing the double bond in resveratrol with a benzothiazole scaffold. Fifty-five benzothiazoles were designed as NQO2 inhibitors and synthesized, comprising five benzothiazole series with 3,5-dimethoxy, 2,4-dimethoxy, 2,5-dimethoxy, 3,4-dimethoxy, and 3,4,5-trimethoxy substituents, the key synthetic step being a Jacobson cyclisation with the appropriate thiobenzamide. All compounds were evaluated in an NQO2 enzyme inhibition assay, with four compounds having IC 50 values of <100 nM. The most active (IC 50 25 nM) was 6-hydroxy-2-(3',5'-dihydroxyphenyl)benzo[d]thiazole (15), a good mimetic of resveratrol. Three of the 3',4',5'-trimethoxybenzothiazole analogues, with 6-methoxy (40, IC 50 51 nM), 6-amino (48, IC 50 79 nM), and 6-acetamide (49, IC 50 31 nM) substituents, were also potent inhibitors of NQO2. Computational modelling indicated the most active compounds exhibited good shape complementarity and polar interactions with the NQO2 active site. Through the inhibition of NQO2, benzothiazole-based compounds may have the potential to enhance the efficiency of cancer therapies or minimise oxidative damage in neuroinflammation.
... It may be found in bone marrow, heart, kidney, liver, blood, and mucous membranes, as in mitochondria and endoplasmic reticulum [35]. 4 Glutathione reductases (GRx) is a flavine nucleotide-dependent enzyme [34], and it has a similar tissue distribution to glutathione peroxide [11]. ...
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Oxidative stress, resulting from an imbalance between free radicals and antioxidants, profoundly influences physiological processes and disease pathogenesis. Free radicals, possessing unpaired electrons, exhibit transient stability but high reactivity, originating from endogenous metabolic processes and exogenous sources like environmental toxins. While essential at low levels, their accumulation leads to oxidative stress, contributing to cellular damage and disease progression. Antioxidants, including enzymatic (e.g., superoxide dismutase, catalase) and non-enzymatic (e.g., glutathione, vitamins C and E) varieties, play pivotal roles in neutralizing free radicals and mitigating oxidative damage. Natural antioxidants, particularly phenolic compounds abundant in plant-based foods, offer diverse health benefits, including anti-inflammatory, anticancer, and antimicrobial properties. Synthetic antioxidants like BHA and BHT are also utilized in food preservation. This review provides insights into the sources, types, and physiological impacts of free radicals, oxidative stress, and antioxidants. Understanding these mechanisms is essential for developing therapeutic interventions against oxidative stress-related disorders and promoting overall health.
... CAT catalyzes the reduction of hydrogen peroxide (H 2 O 2 ) into water and oxygen, preventing oxidative stress and maintaining cellular homeostasis [170]. Glutathione (GSH) reduces (H 2 O 2 ), organic hydro-peroxides, and lipid peroxides via a reaction catalyzed by glutathione peroxidase (GSH-Px), which scavenges O 2 − and OH• [171]. Oxidative compounds within cells can trigger a rise in both enzymatic and non-enzymatic antioxidant defenses as a protective response [172]. ...
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Purpose of Review Nanotechnology has transformed various aspects of contemporary life, technology, and research. This is evident in the rising global demand for and use of nanoparticles, leading to a corresponding increase in their discharge into the environment through diverse human activities. In the last few years, the rampant use of copper oxide nanoparticles (CuO-NPs) has piqued interest. Recent Findings CuO-NPs are widespread and tend to remain in the environment, enabling them to increase in concentration through the food chain and ultimately impact human health. When aquatic organisms are exposed to CuO-NPs, it may cause oxidative stress. This can change proteins, cause lipid peroxidation, and damage DNA. This can ultimately cause cytotoxicity, genotoxicity, and epigenetic changes. Summary CuO-NPs produce reactive oxygen species (ROS), which can have various consequences for organisms and the environment. The objective of the review was to introduce a refreshed audit on the ecotoxicity, a comparison of systems related to CuO-NPs, and an assessment of the safe limit to prevent chronic toxicity across different taxa: aquatic invertebrates, plants, and algae. Additionally, the article briefly discusses the existing knowledge gaps in this area and makes recommendations for future research.
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Frontiers in Clinical Drug Research - Anti Infectives (Volume 9) is a book series that provides updated reviews on the latest advancements in development of pharmaceutical agents for treating infectious diseases. The series covers various topics, including chemistry, pharmacology, molecular biology, and biochemistry of natural and synthetic drugs. Additionally, it addresses multi-drug resistance and pre-clinical/clinical findings on antibiotics, vaccines, antifungal agents, and antitubercular drugs. This series is an invaluable resource for pharmaceutical scientists and postgraduate students, offering critical information to support clinical trials and research in anti-infective drug discovery and epidemiology. The ninth volume presents five in-depth reviews, with topics including mature drugs and antivirals for COVID-19, bacteriocins as potent anti-infective agents, therapeutic interventions targeting free radicals in viral diseases, and a detailed exploration of natural anti-infective agents. The five reviews included in this volume are: - The role of mature drugs in the COVID-19 era - Antivirals to treat COVID-19 - Ribosomally synthesized bacteriocins as potent anti-infective agents - Therapeutic interventions against free radicals in viral diseases - A comprehensive overview of natural anti-infective agents
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The liver plays a vital role in maintaining overall health by regulating various metabolic processes and detoxifying harmful substances. However, it is highly susceptible to damage caused by oxidative stress, which can lead to the development of liver diseases. Antioxidants have emerged as potential therapeutic agents for protecting the liver against oxidative damage and preserving its normal functions. The chapter begins by discussing the mechanisms underlying liver damage and the role of oxidative stress in liver diseases. It then explores the concept of antioxidants and their ability to scavenge free radicals and inhibit oxidative stress. The focus then shifts to medicinal plants that are rich in antioxidants and have been traditionally used for liver ailments. Several well-known medicinal plants are highlighted, including Silybum marianum (milk this tle), Curcuma longa (turmeric), Phyllanthus niruri (stonebreaker), Andrographis paniculata (King of Bitters), Picrorhiza kurroa (Katuki), and Glycyrrhiza glabra (Licorice). Furthermore, it discusses various experimental models and clinical studies that have investigated the efficacy of these antioxidants in liver disease management. Additionally, the chapter addresses the challenges associated with the use of antioxidants in medicinal plants, such as standardization, quality control, and potential herb drug interactions. In conclusion, this book chapter provides a comprehensive overview of the hepatoprotective potential of antioxidants derived from medicinal plants. It underscores the importance of these natural compounds in preventing and managing liver diseases. The information presented here will be valuable to researchers, healthcare professionals, and individuals seeking alternative and complementary approaches to liver health and disease prevention. Keywords: Antioxidants, hepatoprotective, herb-drug interaction, oxidative stress, medicinal plants
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Background A sea cucumber (Stichopus japonicus) is an invertebrate rich in high-quality protein peptides that inhabits the coastal seas around East Asian countries. Such bioactive peptides can be utilized in targeted disease therapies and practical applications in the nutraceutical industry. Methods Bioactive peptides were isolated from Stichopus japonicus through ultrafiltration and Sephadex G-10 size exclusion chromatography. The low-molecular-weight fraction (ACSH-III) showed the highest hydroxyl radical scavenging and angiotensin-converting enzyme (ACE) inhibitory activities. Subsequent purification of ACSH-III resulted in four fractions, of which ACSH-III-F3 and ACSH-III-F4 exhibited significant bioactivity. Results Peptides identified in these fractions, including Phenylalanine-Proline-Threonine-Tyrosine (FPTY) and Tyrosine-Proline-Serine-Tyrosine-Proline-Serine (YPSYPS), were characterized using high-performance liquid chromatography (HPLC) and quadrupole time-of-flight mass spectrometry (QTOF-MS). FPTY demonstrated the most potent antioxidant and antihypertensive activities among these peptides, with IC50 values of 0.11 ± 0.01 mg/mL for hydroxyl radicals and 0.03 ± 0.01 mg/mL for ACE inhibition. Docking simulations revealed strong binding affinities of these peptides to the active site of the ACE, with FPTY displaying interactions similar to those of the synthetic inhibitor lisinopril. Conclusions These findings suggest that the identified peptides, particularly FPTY, have potential applications as natural antioxidants and functional foods.
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