Showing papers in "Antioxidants in 2022"
TL;DR: The current review provides an in-depth look at the fate of ROS in plants, a beneficial role in managing stress and other irregularities, and the biochemical properties and sources of ROS generation, capture systems and the influence of ROS on cell biochemistry are discussed.
Abstract: Reactive oxygen species (ROS, partial reduction or derivatives of free radicals) are highly reactive, dangerous and can cause oxidative cell death. In addition to their role as toxic by-products of aerobic metabolism, ROS play a role in the control and regulation of biological processes such as growth, the cell cycle, programmed cell death, hormone signaling, biotic and abiotic stress reactions and development. ROS always arise in plants as a by-product of several metabolic processes that are located in different cell compartments, or as a result of the inevitable escape of electrons to oxygen from the electron transport activities of chloroplasts, mitochondria and plasma membranes. These reactive species are formed in chloroplasts, mitochondria, plasma membranes, peroxisomes, apoplasts, the endoplasmic reticulum and cell walls. The action of many non-enzymatic and enzymatic antioxidants present in tissues is required for efficient scavenging of ROS generated during various environmental stressors. The current review provides an in-depth look at the fate of ROS in plants, a beneficial role in managing stress and other irregularities. The production sites are also explained with their negative effects. In addition, the biochemical properties and sources of ROS generation, capture systems, the influence of ROS on cell biochemistry and the crosstalk of ROS with other signaling molecules/pathways are discussed.
120 citations
TL;DR: The results of recent studies focusing on the relationship between selenium and pathologies are summarized and discussed in this review, with particular emphasis on advances achieved in the last decade.
Abstract: Selenium is an essential microelement required for a number of biological functions. Selenium—and more specifically the amino acid selenocysteine—is present in at least 25 human selenoproteins involved in a wide variety of essential biological functions, ranging from the regulation of reactive oxygen species (ROS) concentration to the biosynthesis of hormones. These processes also play a central role in preventing and modulating the clinical outcome of several diseases, including cancer, diabetes, Alzheimer’s disease, mental disorders, cardiovascular disorders, fertility impairments, inflammation, and infections (including SARS-CoV-2). Over the past years, a number of studies focusing on the relationship between selenium and such pathologies have been reported. Generally, an adequate selenium nutritional state—and in some cases selenium supplementation—have been related to improved prognostic outcome and reduced risk of developing several diseases. On the other hand, supra-nutritional levels might have adverse effects. The results of recent studies focusing on these topics are summarized and discussed in this review, with particular emphasis on advances achieved in the last decade.
87 citations
TL;DR: In this paper , the authors examined the defensive role of melatonin in photosynthesis, root architecture, and the antioxidant enzymes' activities of tomato seedlings subjected to DR stress, and determined that ME pretreatment could efficiently improve the seedlings growth, root characteristics, leaf photosynthesis and antioxidant machinery under DR stress.
Abstract: Tomato is an important vegetable that is highly sensitive to drought (DR) stress which impairs the development of tomato seedlings. Recently, melatonin (ME) has emerged as a nontoxic, regulatory biomolecule that regulates plant growth and enhances the DR tolerance mechanism in plants. The present study was conducted to examine the defensive role of ME in photosynthesis, root architecture, and the antioxidant enzymes’ activities of tomato seedlings subjected to DR stress. Our results indicated that DR stress strongly suppressed growth and biomass production, inhibited photosynthesis, negatively affected root morphology, and reduced photosynthetic pigments in tomato seedlings. Per contra, soluble sugars, proline, and ROS (reactive oxygen species) were suggested to be improved in seedlings under DR stress. Conversely, ME (100 µM) pretreatment improved the detrimental-effect of DR by restoring chlorophyll content, root architecture, gas exchange parameters and plant growth attributes compared with DR-group only. Moreover, ME supplementation also mitigated the antioxidant enzymes [APX (ascorbate peroxidase), CAT (catalase), DHAR (dehydroascorbate reductase), GST (glutathione S-transferase), GR (glutathione reductase), MDHAR (monodehydroascorbate reductase), POD (peroxidase), and SOD (superoxide dismutase)], non-enzymatic antioxidant [AsA (ascorbate), DHA (dehydroascorbic acid), GSH (glutathione), and GSSG, (oxidized glutathione)] activities, reduced oxidative damage [EL (electrolyte leakage), H2O2 (hydrogen peroxide), MDA (malondialdehyde), and O2•− (superoxide ion)] and osmoregulation (soluble sugars and proline) of tomato seedlings, by regulating gene expression for SOD, CAT, APX, GR, POD, GST, DHAR, and MDHAR. These findings determine that ME pretreatment could efficiently improve the seedlings growth, root characteristics, leaf photosynthesis and antioxidant machinery under DR stress and thereby increasing the seedlings’ adaptability to DR stress.
66 citations
TL;DR: A comprehensive view of the composition of carotenoids, flavonoids, terpenes, and limonoids of citrus fruits and their associated health benefits is provided in this paper .
Abstract: The increased consumption of fruits, vegetables, and whole grains contributes to the reduced risk of many diseases related to metabolic syndrome, including neurodegenerative diseases, cardiovascular disease (CVD), diabetes, and cancer. Citrus, the genus Citrus L., is one of the most important fruit crops, rich in carotenoids, flavonoids, terpenes, limonoids, and many other bioactive compounds of nutritional and nutraceutical value. Moreover, polymethoxylated flavones (PMFs), a unique class of bioactive flavonoids, abundantly occur in citrus fruits. In addition, citrus essential oil, rich in limonoids and terpenes, is an economically important product due to its potent antioxidant, antimicrobial, and flavoring properties. Mechanistic, observational, and intervention studies have demonstrated the health benefits of citrus bioactives in minimizing the risk of metabolic syndrome. This review provides a comprehensive view of the composition of carotenoids, flavonoids, terpenes, and limonoids of citrus fruits and their associated health benefits.
64 citations
TL;DR: The L-enantiomer of ascorbic acid, commonly known as vitamin C, is an indispensable nutrient and plays a key role in retaining the physiological process of humans and animals and its interaction with coexisting components.
Abstract: The L-enantiomer of ascorbic acid is commonly known as vitamin C. It is an indispensable nutrient and plays a key role in retaining the physiological process of humans and animals. L-gulonolactone oxidase, the key enzyme for the de novo synthesis of ascorbic acid, is lacking in some mammals including humans. The functionality of ascorbic acid has prompted the development of foods fortified with this vitamin. As a natural antioxidant, it is expected to protect the sensory and nutritional characteristics of the food. It is thus important to know the degradation of ascorbic acid in the food matrix and its interaction with coexisting components. The biggest challenge in the utilization of ascorbic acid is maintaining its stability and improving its delivery to the active site. The review also includes the current strategies for stabilizing ascorbic acid and the commercial applications of ascorbic acid.
45 citations
TL;DR: In this article , a comprehensive review of the evidence that increasingly supports the concept that, in the case of certain flavonoids, the oxidation of phenolics emerges as a mechanism that markedly amplifies their original antioxidant properties.
Abstract: Flavonoids display a broad range of health-promoting bioactivities. Among these, their capacity to act as antioxidants has remained most prominent. The canonical reactive oxygen species (ROS)-scavenging mode of the antioxidant action of flavonoids relies on the high susceptibility of their phenolic moieties to undergo oxidation. As a consequence, upon reaction with ROS, the antioxidant capacity of flavonoids is severely compromised. Other phenol-compromising reactions, such as those involved in the biotransformation of flavonoids, can also markedly affect their antioxidant properties. In recent years, however, increasing evidence has indicated that, at least for some flavonoids, the oxidation of such residues can in fact markedly enhance their original antioxidant properties. In such apparent paradoxical cases, the antioxidant activity arises from the pro-oxidant and/or electrophilic character of some of their oxidation-derived metabolites and is exerted by activating the Nrf2–Keap1 pathway, which upregulates the cell’s endogenous antioxidant capacity, and/or, by preventing the activation of the pro-oxidant and pro-inflammatory NF-κB pathway. This review focuses on the effects that the oxidative and/or non-oxidative modification of the phenolic groups of flavonoids may have on the ability of the resulting metabolites to promote direct and/or indirect antioxidant actions. Considering the case of a metabolite resulting from the oxidation of quercetin, we offer a comprehensive description of the evidence that increasingly supports the concept that, in the case of certain flavonoids, the oxidation of phenolics emerges as a mechanism that markedly amplifies their original antioxidant properties. An overlooked topic of great phytomedicine potential is thus unraveled.
45 citations
TL;DR: While GPX4 is the most potent anti-ferroptotic enzyme that is known to reduce lipid peroxides to alcohols, other antioxidative enzymes are also indirectly involved in protection against ferroptosis, and several low molecular weight compounds that include α-tocopherol, ascorbate, and nitric oxide also efficiently neutralize radical electrons, thereby suppressing ferroPTosis.
Abstract: Superoxide is a primary oxygen radical that is produced when an oxygen molecule receives one electron. Superoxide dismutase (SOD) plays a primary role in the cellular defense against an oxidative insult by ROS. However, the resulting hydrogen peroxide is still reactive and, in the presence of free ferrous iron, may produce hydroxyl radicals and exacerbate diseases. Polyunsaturated fatty acids are the preferred target of hydroxyl radicals. Ferroptosis, a type of necrotic cell death induced by lipid peroxides in the presence of free iron, has attracted considerable interest because of its role in the pathogenesis of many diseases. Radical electrons, namely those released from mitochondrial electron transfer complexes, and those produced by enzymatic reactions, such as lipoxygenases, appear to cause lipid peroxidation. While GPX4 is the most potent anti-ferroptotic enzyme that is known to reduce lipid peroxides to alcohols, other antioxidative enzymes are also indirectly involved in protection against ferroptosis. Moreover, several low molecular weight compounds that include α-tocopherol, ascorbate, and nitric oxide also efficiently neutralize radical electrons, thereby suppressing ferroptosis. The removal of radical electrons in the early stages is of primary importance in protecting against ferroptosis and other diseases that are related to oxidative stress.
42 citations
TL;DR: The evidence that CA or rosemary extracts containing CA may represent an effective countermeasure against both acute and chronic pathological events initiated by SARS-CoV-2 infection as well as other chronic neurodegenerative diseases including AD and PD is discussed.
Abstract: Rosemary (Rosmarinus officinalis [family Lamiaceae]), an herb of economic and gustatory repute, is employed in traditional medicines in many countries. Rosemary contains carnosic acid (CA) and carnosol (CS), abietane-type phenolic diterpenes, which account for most of its biological and pharmacological actions, although claims have also been made for contributions of another constituent, rosmarinic acid. This review focuses on the potential applications of CA and CS for Alzheimer’s disease (AD), Parkinson’s disease (PD), and coronavirus disease 2019 (COVID-19), in part via inhibition of the NLRP3 inflammasome. CA exerts antioxidant, anti-inflammatory, and neuroprotective effects via phase 2 enzyme induction initiated by activation of the KEAP1/NRF2 transcriptional pathway, which in turn attenuates NLRP3 activation. In addition, we propose that CA-related compounds may serve as therapeutics against the brain-related after-effects of SARS-CoV-2 infection, termed “long-COVID.” One factor that contributes to COVID-19 is cytokine storm emanating from macrophages as a result of unregulated inflammation in and around lung epithelial and endovascular cells. Additionally, neurological aftereffects such as anxiety and “brain fog” are becoming a major issue for both the pandemic and post-pandemic period. Many reports hold that unregulated NLRP3 inflammasome activation may potentially contribute to the severity of COVID-19 and its aftermath. It is therefore possible that suppression of NLRP3 inflammasome activity may prove efficacious against both acute lung disease and chronic neurological after-effects. Because CA has been shown to not only act systemically but also to penetrate the blood–brain barrier and reach the brain parenchyma to exert neuroprotective effects, we discuss the evidence that CA or rosemary extracts containing CA may represent an effective countermeasure against both acute and chronic pathological events initiated by SARS-CoV-2 infection as well as other chronic neurodegenerative diseases including AD and PD.
40 citations
TL;DR: This review critically discusses the recent developments in studies of the chemistry and antioxidant activity, marketing trends, dietary sources, extraction, bioaccessibility and bioavailability, encapsulation methods, dietary intake, and health benefits of CARs.
Abstract: Natural carotenoids (CARs), viz. β-carotene, lutein, astaxanthin, bixin, norbixin, capsanthin, lycopene, canthaxanthin, β-Apo-8-carotenal, zeaxanthin, and β-apo-8-carotenal-ester, are being studied as potential candidates in fields such as food, feed, nutraceuticals, and cosmeceuticals. CAR research is advancing in the following three major fields: (1) CAR production from natural sources and optimization of its downstream processing; (2) encapsulation for enhanced physical and chemical properties; and (3) preclinical, clinical, and epidemiological studies of CARs’ health benefits. This review critically discusses the recent developments in studies of the chemistry and antioxidant activity, marketing trends, dietary sources, extraction, bioaccessibility and bioavailability, encapsulation methods, dietary intake, and health benefits of CARs. Preclinical, clinical, and epidemiological studies on cancer, obesity, type 2 diabetes (T2D), cardiovascular diseases (CVD), osteoporosis, neurodegenerative disease, mental health, eye, and skin health are also discussed.
40 citations
TL;DR: The correlation study revealed that these drought-resistant accessions contain plentiful proximate, nutraceuticals, phytopigments, bioactive phytochemicals, and antioxidant potentiality as discussed by the authors .
Abstract: Leafy vegetables are susceptible to drought stress. Amaranthus tricolor vegetables are resistant to abiotic stress, including drought, and are a source of ample natural phytochemicals of interest to the food industry due to their benefits to consumers’ health. Hence, the selected drought-resistant amaranth genotypes were evaluated for phytochemicals and antioxidant activity in an RCBD study with three replicates. The selected drought-resistant amaranth accessions contained ample carbohydrates, protein, moisture, and dietary fiber. We noticed many macroelements and microelements including iron, copper, manganese, zinc, sodium, molybdenum, boron, potassium, calcium, magnesium, phosphorus, and sulfur; adequate phytopigments, including betacyanins, betalains, betaxanthins, carotenoids, and chlorophylls; plentiful bioactive phytochemicals, including ascorbic acid, flavonoids, polyphenols, and beta-carotene; and antioxidant potential in the selected drought-resistant amaranth accessions. The drought-resistant amaranth accessions VA14 and VA16 were proven to have high ascorbic acid, beta-carotene, and polyphenol levels. The drought-resistant accessions VA12 and VA14 had high flavonoid levels. The drought-resistant accessions VA3, VA14, and VA16 had high AC both in regard to both DPPH and ABTS+. These drought-resistant accessions, VA3, VA14, and VA16, can be utilized as high-yielding varieties with antioxidant profiles for purposes of drinks. The correlation study revealed that bioactive phytopigments and phytochemicals of amaranth accessions had good free radical quenching capacity against 2,2′-azino-bis (3-ethylbenzothiazo-6-sulfonic acid) and diphenyl-1-picrylhydrazyl, equivalent to Trolox. It was revealed in the present study that these drought-resistant accessions contain plentiful proximate, nutraceuticals, phytopigments, bioactive phytochemicals, and antioxidant potentiality. Their drought resistance and quenching of ROS offer huge prospects for the promotion of health benefits and the feeding of communities in drought-prone semiarid and arid areas of the globe, especially those deficient in nutraceuticals, phytopigments, and antioxidants.
40 citations
TL;DR: A knowledge of the mechanisms responsible for creating oxidative stress within the human ejaculate is essential in order to develop better antioxidant strategies that avoid the unintentional creation of its reductive counterpart.
Abstract: Reactive oxygen species (ROS) play a critical role in defining the functional competence of human spermatozoa. When generated in moderate amounts, ROS promote sperm capacitation by facilitating cholesterol efflux from the plasma membrane, enhancing cAMP generation, inducing cytoplasmic alkalinization, increasing intracellular calcium levels, and stimulating the protein phosphorylation events that drive the attainment of a capacitated state. However, when ROS generation is excessive and/or the antioxidant defences of the reproductive system are compromised, a state of oxidative stress may be induced that disrupts the fertilizing capacity of the spermatozoa and the structural integrity of their DNA. This article focusses on the sources of ROS within this system and examines the circumstances under which the adequacy of antioxidant protection might become a limiting factor. Seminal leukocyte contamination can contribute to oxidative stress in the ejaculate while, in the germ line, the dysregulation of electron transport in the sperm mitochondria, elevated NADPH oxidase activity, or the excessive stimulation of amino acid oxidase action are all potential contributors to oxidative stress. A knowledge of the mechanisms responsible for creating such stress within the human ejaculate is essential in order to develop better antioxidant strategies that avoid the unintentional creation of its reductive counterpart.
TL;DR: Evidence from the literature is reported describing the effect of NRF2 on ovarian cancer, with a focus on its function in drug resistance,NRF2 natural and synthetic modulators and its protective function in normal ovarian preservation.
Abstract: Among gynaecologic malignancies, ovarian cancer is one of the most dangerous, with a high fatality rate and relapse due to the occurrence of chemoresistance. Many researchers demonstrated that oxidative stress is involved in tumour occurrence, growth and development. Nuclear factor erythroid 2-related factor 2 (NRF2) is an important transcription factor, playing an important role in protecting against oxidative damage. Increased levels of Reactive Oxygen Species (ROS) activate NRF2 signalling, inducing the expression of antioxidant enzymes, such as haem oxygenase (HO-1), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), that protect cells against oxidative stress. However, NRF2 activation in cancer cells is responsible for the development of chemoresistance, inactivating drug-mediated oxidative stress that normally leads to cancer cells’ death. In this review, we report evidence from the literature describing the effect of NRF2 on ovarian cancer, with a focus on its function in drug resistance, NRF2 natural and synthetic modulators and its protective function in normal ovarian preservation.
TL;DR: This review discusses the existing knowledge on oxidative stress in the skin, examining sources and defenses, giving particular consideration to melanocytes, and analyzed the possibility to exploit the induction of oxidative stress as a therapeutic strategy to improve the effectiveness of therapeutic management of melanoma.
Abstract: The skin is constantly exposed to exogenous and endogenous sources of reactive oxygen species (ROS). An adequate balance between ROS levels and antioxidant defenses is necessary for the optimal cell and tissue functions, especially for the skin, since it must face additional ROS sources that do not affect other tissues, including UV radiation. Melanocytes are more exposed to oxidative stress than other cells, also due to the melanin production process, which itself contributes to generating ROS. There is an increasing amount of evidence that oxidative stress may play a role in many skin diseases, including melanoma, being the primary cause or being a cofactor that aggravates the primary condition. Indeed, oxidative stress is emerging as another major force involved in all the phases of melanoma development, not only in the arising of the malignancy but also in the progression toward the metastatic phenotype. Furthermore, oxidative stress seems to play a role also in chemoresistance and thus has become a target for therapy. In this review, we discuss the existing knowledge on oxidative stress in the skin, examining sources and defenses, giving particular consideration to melanocytes. Therefore, we focus on the significance of oxidative stress in melanoma, thus analyzing the possibility to exploit the induction of oxidative stress as a therapeutic strategy to improve the effectiveness of therapeutic management of melanoma.
TL;DR: Evidence from human studies indicate that HO-1 expression may represent a biomarker of oxidative stress in various clinical conditions, while increases in serum BR levels have been correlated inversely to risk of CVD and metabolic disease.
Abstract: The heme oxygenase (HO) enzyme system catabolizes heme to carbon monoxide (CO), ferrous iron, and biliverdin-IXα (BV), which is reduced to bilirubin-IXα (BR) by biliverdin reductase (BVR). HO activity is represented by two distinct isozymes, the inducible form, HO-1, and a constitutive form, HO-2, encoded by distinct genes (HMOX1, HMOX2, respectively). HO-1 responds to transcriptional activation in response to a wide variety of chemical and physical stimuli, including its natural substrate heme, oxidants, and phytochemical antioxidants. The expression of HO-1 is regulated by NF-E2-related factor-2 and counter-regulated by Bach-1, in a heme-sensitive manner. Additionally, HMOX1 promoter polymorphisms have been associated with human disease. The induction of HO-1 can confer protection in inflammatory conditions through removal of heme, a pro-oxidant and potential catalyst of lipid peroxidation, whereas iron released from HO activity may trigger ferritin synthesis or ferroptosis. The production of heme-derived reaction products (i.e., BV, BR) may contribute to HO-dependent cytoprotection via antioxidant and immunomodulatory effects. Additionally, BVR and BR have newly recognized roles in lipid regulation. CO may alter mitochondrial function leading to modulation of downstream signaling pathways that culminate in anti-apoptotic, anti-inflammatory, anti-proliferative and immunomodulatory effects. This review will present evidence for beneficial effects of HO-1 and its reaction products in human diseases, including cardiovascular disease (CVD), metabolic conditions, including diabetes and obesity, as well as acute and chronic diseases of the liver, kidney, or lung. Strategies targeting the HO-1 pathway, including genetic or chemical modulation of HO-1 expression, or application of BR, CO gas, or CO donor compounds show therapeutic potential in inflammatory conditions, including organ ischemia/reperfusion injury. Evidence from human studies indicate that HO-1 expression may represent a biomarker of oxidative stress in various clinical conditions, while increases in serum BR levels have been correlated inversely to risk of CVD and metabolic disease. Ongoing human clinical trials investigate the potential of CO as a therapeutic in human disease.
TL;DR: In this article , the authors highlight new scientific data on the moringa leaves containing nutrient and bioactive profiles, bioavailability, health benefits, and uses in various food items.
Abstract: Based on the availability of many nutrients, Moringa oleifera tree leaves have been widely employed as nutrients and nutraceuticals in recent years. The leaves contain a small amount of anti-nutritional factors and are abundant in innumerable bioactive compounds. Recently, in several in vivo and in vitro investigations, moringa leaves’ bioactive components and functionality are highlighted. Moringa leaves provide several health advantages, including anti-diabetic, antibacterial, anti-cancer, and anti-inflammatory properties. The high content of phytochemicals, carotenoids, and glucosinolates is responsible for the majority of these activities as reported in the literature. Furthermore, there is growing interest in using moringa as a value-added ingredient in the development of functional foods. Despite substantial study into identifying and measuring these beneficial components from moringa leaves, bioaccessibility and bioavailability studies are lacking. This review emphasizes recent scientific evidence on the dietary and bioactive profiles of moringa leaves, bioavailability, health benefits, and applications in various food products. This study highlights new scientific data on the moringa leaves containing nutrient and bioactive profiles, bioavailability, health benefits, and uses in various food items. Moringa has been extensively used as a health-promoting food additive because of its potent protection against various diseases and the widespread presence of environmental toxins. More research is needed for utilization as well as to study medicinal effects and bioaccesibility of these leaves for development of various drugs and functional foods.
TL;DR: Investigations in animal models of diabetic cardiomyopathy have consistently demonstrated that increased expression of the primary antioxidant enzymes attenuates myocardial pathology and improves cardiac function.
Abstract: Type 2 diabetes is a redox disease. Oxidative stress and chronic inflammation induce a switch of metabolic homeostatic set points, leading to glucose intolerance. Several diabetes-specific mechanisms contribute to prominent oxidative distress in the heart, resulting in the development of diabetic cardiomyopathy. Mitochondrial overproduction of reactive oxygen species in diabetic subjects is not only caused by intracellular hyperglycemia in the microvasculature but is also the result of increased fatty oxidation and lipotoxicity in cardiomyocytes. Mitochondrial overproduction of superoxide anion radicals induces, via inhibition of glyceraldehyde 3-phosphate dehydrogenase, an increased polyol pathway flux, increased formation of advanced glycation end-products (AGE) and activation of the receptor for AGE (RAGE), activation of protein kinase C isoforms, and an increased hexosamine pathway flux. These pathways not only directly contribute to diabetic cardiomyopathy but are themselves a source of additional reactive oxygen species. Reactive oxygen species and oxidative distress lead to cell dysfunction and cellular injury not only via protein oxidation, lipid peroxidation, DNA damage, and oxidative changes in microRNAs but also via activation of stress-sensitive pathways and redox regulation. Investigations in animal models of diabetic cardiomyopathy have consistently demonstrated that increased expression of the primary antioxidant enzymes attenuates myocardial pathology and improves cardiac function.
TL;DR: In this article , Abscisic acid and NO synergistically interact to reduce the heat stress effects on photosynthesis and growth via reducing the content of H2O2 and thiobarbituric acid reactive substances (TBARS), as well as maximizing osmolytes production and the activity and expression of antioxidant enzymes.
Abstract: Nitric oxide (NO) and abscisic acid (ABA) play a significant role to combat abiotic stress. Application of 100 µM sodium nitroprusside (SNP, NO donor) or ABA alleviated heat stress effects on photosynthesis and growth of wheat (Triticum aestivum L.) plants exposed to 40 °C for 6 h every day for 15 days. We have shown that ABA and NO synergistically interact to reduce the heat stress effects on photosynthesis and growth via reducing the content of H2O2 and thiobarbituric acid reactive substances (TBARS), as well as maximizing osmolytes production and the activity and expression of antioxidant enzymes. The inhibition of NO and ABA using c-PTIO (2-4 carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) and fluridone (Flu), respectively, reduced the osmolyte and antioxidant metabolism and heat stress tolerance. The inhibition of NO significantly reduced the ABA-induced osmolytes and antioxidant metabolism, exhibiting that the function of ABA in the alleviation of heat stress was NO dependent and can be enhanced with NO supplementation.Thus, regulating the activity and expression of antioxidant enzymes together with osmolytes production could act as a possible strategy for heat tolerance.
TL;DR: In this article , a maize seedling was subjected to drought stress of 40-45% field capacity (FC) at the five-leaf stage, followed by a soil drenching of melatonin 100 µM and three nitrogen levels (200, 250, and 300 kg ha−1).
Abstract: Melatonin plays an important role in numerous vital life processes of animals and has recently captured the interests of plant biologists because of its potent role in plants. As well as its possible contribution to photoperiodic processes, melatonin is believed to act as a growth regulator and/or as a direct free radical scavenger/indirect antioxidant. However, identifying a precise concentration of melatonin with an optimum nitrogen level for a particular application method to improve plant growth requires identification and clarification. This work establishes inimitable findings by optimizing the application of melatonin with an optimum level of nitrogen, alleviating the detrimental effects of drought stress in maize seedlings. Maize seedlings were subjected to drought stress of 40–45% field capacity (FC) at the five-leaf stage, followed by a soil drenching of melatonin 100 µM and three nitrogen levels (200, 250, and 300 kg ha−1) to consider the changes in maize seedling growth. Our results showed that drought stress significantly inhibited the physiological and biochemical parameters of maize seedlings. However, the application of melatonin with nitrogen remarkably improved the plant growth attributes, chlorophyll pigments, fluorescence, and gas exchange parameters. Moreover, melatonin and nitrogen application profoundly reduced the reactive oxygen species (ROS) accumulation by increasing maize antioxidant and nitrogen metabolism enzyme activities under drought-stress conditions. It was concluded that the mitigating potential of 100 µM melatonin with an optimum level of nitrogen (250 kg N ha−1) improves the plant growth, photosynthetic efficiency, and enzymatic activity of maize seedling under drought-stress conditions.
TL;DR: This review provides a brief introduction to the ANS network, its connections to the HPA axis and its stress responses and gives an overview of the critical implications of ANS in health and disease—focused specifically on the immune system, cardiovascular, oxidative stress and metabolic dysregulation.
Abstract: Studies show that the autonomic nervous system (ANS) has an important impact on health in general. In response to environmental demands, homeostatic processes are often compromised, therefore determining an increase in the sympathetic nervous system (SNS)’s functions and a decrease in the parasympathetic nervous system (PNS)’s functions. In modern societies, chronic stress associated with an unhealthy lifestyle contributes to ANS dysfunction. In this review, we provide a brief introduction to the ANS network, its connections to the HPA axis and its stress responses and give an overview of the critical implications of ANS in health and disease—focused specifically on the immune system, cardiovascular, oxidative stress and metabolic dysregulation. The hypothalamic–pituitary–adrenal axis (HPA), the SNS and more recently the PNS have been identified as regulating the immune system. The HPA axis and PNS have anti-inflammatory effects and the SNS has been shown to have both pro- and anti-inflammatory effects. The positive impact of physical exercise (PE) is well known and has been studied by many researchers, but its negative impact has been less studied. Depending on the type, duration and individual characteristics of the person doing the exercise (age, gender, disease status, etc.), PE can be considered a physiological stressor. The negative impact of PE seems to be connected with the oxidative stress induced by effort.
TL;DR: A review of the antibacterial properties, underlying molecular mechanism of curcumin, and discuss its combination use, nano-formulations, safety, and current challenges towards development as an antibacterial agent is presented in this article .
Abstract: The rapid spread of antibiotic resistance and lack of effective drugs for treating infections caused by multi-drug resistant bacteria in animal and human medicine have forced us to find new antibacterial strategies. Natural products have served as powerful therapeutics against bacterial infection and are still an important source for the discovery of novel antibacterial drugs. Curcumin, an important constituent of turmeric, is considered safe for oral consumption to treat bacterial infections. Many studies showed that curcumin exhibited antibacterial activities against Gram-negative and Gram-positive bacteria. The antibacterial action of curcumin involves the disruption of the bacterial membrane, inhibition of the production of bacterial virulence factors and biofilm formation, and the induction of oxidative stress. These characteristics also contribute to explain how curcumin acts a broad-spectrum antibacterial adjuvant, which was evidenced by the markedly additive or synergistical effects with various types of conventional antibiotics or non-antibiotic compounds. In this review, we summarize the antibacterial properties, underlying molecular mechanism of curcumin, and discuss its combination use, nano-formulations, safety, and current challenges towards development as an antibacterial agent. We hope that this review provides valuable insight, stimulates broader discussions, and spurs further developments around this promising natural product.
TL;DR: A comprehensive analysis of the potential of antioxidant therapy, challenges in their clinical translation, and the role nanoparticles/drug delivery systems could play in addressing these challenges is provided.
Abstract: Free radicals are formed as a part of normal metabolic activities but are neutralized by the endogenous antioxidants present in cells/tissue, thus maintaining the redox balance. This redox balance is disrupted in certain neuropathophysiological conditions, causing oxidative stress, which is implicated in several progressive neurodegenerative diseases. Following neuronal injury, secondary injury progression is also caused by excessive production of free radicals. Highly reactive free radicals, mainly the reactive oxygen species (ROS) and reactive nitrogen species (RNS), damage the cell membrane, proteins, and DNA, which triggers a self-propagating inflammatory cascade of degenerative events. Dysfunctional mitochondria under oxidative stress conditions are considered a key mediator in progressive neurodegeneration. Exogenous delivery of antioxidants holds promise to alleviate oxidative stress to regain the redox balance. In this regard, natural and synthetic antioxidants have been evaluated. Despite promising results in preclinical studies, clinical translation of antioxidants as a therapy to treat neurodegenerative diseases remains elusive. The issues could be their low bioavailability, instability, limited transport to the target tissue, and/or poor antioxidant capacity, requiring repeated and high dosing, which cannot be administered to humans because of dose-limiting toxicity. Our laboratory is investigating nanoparticle-mediated delivery of antioxidant enzymes to address some of the above issues. Apart from being endogenous, the main advantage of antioxidant enzymes is their catalytic mechanism of action; hence, they are significantly more effective at lower doses in detoxifying the deleterious effects of free radicals than nonenzymatic antioxidants. This review provides a comprehensive analysis of the potential of antioxidant therapy, challenges in their clinical translation, and the role nanoparticles/drug delivery systems could play in addressing these challenges.
TL;DR: All high-altitude pathologies are related to oxidative stress, as indicated by increases in the malondialdehyde (MDA) biomarker and decreases in superoxide dismutase (SOD) and glutathione peroxidase (GPx) antioxidant activity.
Abstract: Several diseases associated with high-altitude exposure affect unacclimated individuals. These diseases include acute mountain sickness (AMS), high-altitude cerebral edema (HACE), high-altitude pulmonary edema (HAPE), chronic mountain sickness (CMS), and, notably, high-altitude pulmonary hypertension (HAPH), which can eventually lead to right ventricle hypertrophy and heart failure. The development of these pathologies involves different molecules and molecular pathways that might be related to oxidative stress. Studies have shown that acute, intermittent, and chronic exposure to hypobaric hypoxia induce oxidative stress, causing alterations to molecular pathways and cellular components (lipids, proteins, and DNA). Therefore, the aim of this review is to discuss the oxidative molecules and pathways involved in the development of high-altitude diseases. In summary, all high-altitude pathologies are related to oxidative stress, as indicated by increases in the malondialdehyde (MDA) biomarker and decreases in superoxide dismutase (SOD) and glutathione peroxidase (GPx) antioxidant activity. In addition, in CMS, the levels of 8-iso-PGF2α and H2O2 are increased, and evidence strongly indicates an increase in Nox4 activity in HAPH. Therefore, antioxidant treatments seem to be a promising approach to mitigating high-altitude pathologies.
TL;DR: This review provides a summary of their modulation through in vitro and in vivo evidence (animal models and humans), as well as their possible actions through intestinal barrier function and gut microbes to better investigate the health benefits of dietary polyphenols.
Abstract: Polyphenols, which are probably the most important secondary metabolites produced by plants, have attracted tremendous attention due to their health-promoting effects, including their antioxidant, anti-inflammatory, antibacterial, anti-adipogenic, and neuro-protective activities, as well as health properties. However, due to their complicated structures and high molecular weights, a large proportion of dietary polyphenols remain unabsorbed along the gastrointestinal tract, while in the large intestine they are biotransformed into bioactive, low-molecular-weight phenolic metabolites through the residing gut microbiota. Dietary polyphenols can modulate the composition of intestinal microbes, and in turn, gut microbes catabolize polyphenols to release bioactive metabolites. To better investigate the health benefits of dietary polyphenols, this review provides a summary of their modulation through in vitro and in vivo evidence (animal models and humans), as well as their possible actions through intestinal barrier function and gut microbes. This review aims to provide a basis for better understanding the relationship between dietary polyphenols, gut microbiota, and host health.
TL;DR: The study revealed that walnut-enriched diets had statistically significant decreasing effects for triglyceride, total cholesterol, and LDL cholesterol concentrations on some inflammatory markers and presented no consequences on anthropometric and glycemic parameters, emphasizing the benefits of including walnuts in the dietary plans of this age group.
Abstract: Biomarkers of metabolic syndrome and inflammation are pathophysiological predictors and factors of senescence and age-related diseases. Recent evidence showed that particular diet components, such as walnuts rich in antioxidant bioactive compounds and with a balanced lipid profile, could have positive outcomes on human health. A systematic search in PubMed, EMBASE, Cochrane Library, Scopus, and ClinicalTrials.gov databases was performed to retrieve randomized controlled trials published from the beginning of each database through November 2021, reporting on the outcomes of walnut consumption over 22 metabolic syndrome and inflammatory markers in middle-aged and older adults. The search strategy rendered 17 studies in the final selection, including 11 crossover and 6 parallel trials. The study revealed that walnut-enriched diets had statistically significant decreasing effects for triglyceride, total cholesterol, and LDL cholesterol concentrations on some inflammatory markers and presented no consequences on anthropometric and glycemic parameters. Although further studies and better-designed ones are needed to strengthen these findings, the results emphasize the benefits of including walnuts in the dietary plans of this age group.
TL;DR: There is a marked increase in oxidative stress in the lungs of patients with COPD, as measured by increased exhaled 8-isoprostane, ethane, and hydrogen peroxide in the breath as mentioned in this paper .
Abstract: There is a marked increase in oxidative stress in the lungs of patients with COPD, as measured by increased exhaled 8-isoprostane, ethane, and hydrogen peroxide in the breath. The lung may be exposed to exogenous oxidative stress from cigarette smoking and indoor or outdoor air pollution and to endogenous oxidative stress from reactive oxygen species released from activated inflammatory cells, particularly neutrophils and macrophages, in the lungs. Oxidative stress in COPD may be amplified by a reduction in endogenous antioxidants and poor intake of dietary antioxidants. Oxidative stress is a major driving mechanism of COPD through the induction of chronic inflammation, induction of cellular senescence and impaired autophagy, reduced DNA repair, increased autoimmunity, increased mucus secretion, and impaired anti-inflammatory response to corticosteroids. Oxidative stress, therefore, drives the pathology of COPD and may increase disease progression, amplify exacerbations, and increase comorbidities through systemic oxidative stress. This suggests that antioxidants may be effective as disease-modifying treatments. Unfortunately, thiol-based antioxidants, such as N-acetylcysteine, have been poorly effective, as they are inactivated by oxidative stress in the lungs, so there is a search for more effective and safer antioxidants. New antioxidants in development include mitochondria-targeted antioxidants, NOX inhibitors, and activators of the transcription factor Nrf2, which regulates several antioxidant genes.
TL;DR: In this paper , a zinc oxide (ZnO) NPs have been synthesized employing an aqueous leaf extract of Pelargonium odoratissimum (L.) as a reducing agent, which can be used as a safe alternative to synthetic substances as well as a potential candidate for antioxidants, antibacterial and anti-inflammatory uses in the biomedical and pharmaceutical industries.
Abstract: Nanoparticles (NPs) exhibit distinct features compared to traditional physico-chemical synthesis and they have many applications in a wide range of fields of life sciences such as surface coating agents, catalysts, food packaging, corrosion protection, environmental remediation, electronics, biomedical and antimicrobial. Green-synthesized metal NPs, mainly from plant sources, have gained a lot of attention due to their intrinsic characteristics like eco-friendliness, rapidity and cost-effectiveness. In this study, zinc oxide (ZnO) NPs have been synthesized employing an aqueous leaf extract of Pelargonium odoratissimum (L.) as a reducing agent; subsequently, the biosynthesized ZnO NPs were characterized by ultraviolet-visible spectroscopy (UV-Vis), dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and energy-dispersive X-ray spectroscopy (EDX), high-resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED). Moreover, aqueous plant leaf extract was subjected to both qualitative and quantitative analysis. Antioxidant activity of ZnO NPs was assessed by DPPH assay, with varying concentrations of ZnO NPs, which revealed scavenging activity with IC50 = 28.11 μg mL−1. Furthermore, the anti-bacterial efficacy of the green synthesized ZnO NPs against four foodborne pathogenic bacterial strains was examined using the disk diffusion assay, and Staphylococcus aureus (ATCC 8095), Pseudomonas aeruginosa (ATCC10662) and Escherichia coli (ATCC 25922) were found to be the most sensitive against biosynthesized ZnO NPs, whereas the least sensitivity was shown by Bacillus cereus (ATCC 13753). The anti-inflammatory effect was also evaluated for both ZnO NPs and the aqueous leaf extract of P. odoratissimum through the human red blood cells (HRBC) membrane stabilization method (MSM) in vitro models which includes hypotonicity-induced hemolysis. A maximum membrane stabilization of ZnO NPs was found to be 95.6% at a dose of 1000 μg mL−1 compared with the standard indomethacin. The results demonstrated that leaf extract of P. odoratissimum is suitable for synthesizing ZnO NPs, with antioxidant, antibacterial as well as superior anti-inflammatory activity by improving the membrane stability of lysosome cells, which have physiological properties similar to erythrocyte membrane cells and have no hemolytic activity. Overall, this study provides biosynthesized ZnO NPs that can be used as a safe alternative to synthetic substances as well as a potential candidate for antioxidants, antibacterial and anti-inflammatory uses in the biomedical and pharmaceutical industries.
TL;DR: Owing to all the antioxidant, anti-diabetic, and anti-hypertensive properties, lycopene provides a potential nutraceutical with a protective and curing ability against coronary artery disease and hypertension.
Abstract: Lycopene is a bioactive red pigment found in plants, especially in red fruits and vegetables, including tomato, pink guava, papaya, pink grapefruit, and watermelon. Several research reports have advocated its positive impact on human health and physiology. For humans, lycopene is an essential substance obtained from dietary sources to fulfil the body requirements. The production of reactive oxygen species (ROS) causing oxidative stress and downstream complications include one of the major health concerns worldwide. In recent years, oxidative stress and its counter strategies have attracted biomedical research in order to manage the emerging health issues. Lycopene has been reported to directly interact with ROS, which can help to prevent chronic diseases, including diabetes and neurodegenerative and cardiovascular diseases. In this context, the present review article was written to provide an accumulative account of protective and ameliorative effects of lycopene on coronary artery disease (CAD) and hypertension, which are the leading causes of death worldwide. Lycopene is a potent antioxidant that fights ROS and, subsequently, complications. It reduces blood pressure via inhibiting the angiotensin-converting enzyme and regulating nitrous oxide bioavailability. It plays an important role in lowering of LDL (low-density lipoproteins) and improving HDL (high-density lipoproteins) levels to minimize atherosclerosis, which protects the onset of coronary artery disease and hypertension. Various studies have advocated that lycopene exhibited a combating competence in the treatment of these diseases. Owing to all the antioxidant, anti-diabetic, and anti-hypertensive properties, lycopene provides a potential nutraceutical with a protective and curing ability against coronary artery disease and hypertension.
TL;DR: New therapies based on redox mechanisms have emerged to treat acute inflammation with positive results, which highlights the relevance of redox signaling as a master regulator of macrophage reprogramming during acute inflammation.
Abstract: Macrophage polarization refers to the process by which macrophages can produce two distinct functional phenotypes: M1 or M2. The balance between both strongly affects the progression of inflammatory disorders. Here, we review how redox signals regulate macrophage polarization and reprogramming during acute inflammation. In M1, macrophages augment NADPH oxidase isoform 2 (NOX2), inducible nitric oxide synthase (iNOS), synaptotagmin-binding cytoplasmic RNA interacting protein (SYNCRIP), and tumor necrosis factor receptor-associated factor 6 increase oxygen and nitrogen reactive species, which triggers inflammatory response, phagocytosis, and cytotoxicity. In M2, macrophages down-regulate NOX2, iNOS, SYNCRIP, and/or up-regulate arginase and superoxide dismutase type 1, counteract oxidative and nitrosative stress, and favor anti-inflammatory and tissue repair responses. M1 and M2 macrophages exhibit different metabolic profiles, which are tightly regulated by redox mechanisms. Oxidative and nitrosative stress sustain the M1 phenotype by activating glycolysis and lipid biosynthesis, but by inhibiting tricarboxylic acid cycle and oxidative phosphorylation. This metabolic profile is reversed in M2 macrophages because of changes in the redox state. Therefore, new therapies based on redox mechanisms have emerged to treat acute inflammation with positive results, which highlights the relevance of redox signaling as a master regulator of macrophage reprogramming.
TL;DR: Key insights are outlined into the pharmacological abilities of stigmasterol and the specific mechanisms of action underlying some of these effects.
Abstract: Stigmasterol is an unsaturated phytosterol belonging to the class of tetracyclic triterpenes. It is one of the most common plant sterols, found in a variety of natural sources, including vegetable fats or oils from many plants. Currently, stigmasterol has been examined via in vitro and in vivo assays and molecular docking for its various biological activities on different metabolic disorders. The findings indicate potent pharmacological effects such as anticancer, anti-osteoarthritis, anti-inflammatory, anti-diabetic, immunomodulatory, antiparasitic, antifungal, antibacterial, antioxidant, and neuroprotective properties. Indeed, stigmasterol from plants and algae is a promising molecule in the development of drugs for cancer therapy by triggering intracellular signaling pathways in numerous cancers. It acts on the Akt/mTOR and JAK/STAT pathways in ovarian and gastric cancers. In addition, stigmasterol markedly disrupted angiogenesis in human cholangiocarcinoma by tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor receptor-2 (VEGFR-2) signaling down-regulation. The association of stigmasterol and sorafenib promoted caspase-3 activity and down-regulated levels of the anti-apoptotic protein Bcl-2 in breast cancer. Antioxidant activities ensuring lipid peroxidation and DNA damage lowering conferred to stigmasterol chemoprotective activities in skin cancer. Reactive oxygen species (ROS) regulation also contributes to the neuroprotective effects of stigmasterol, as well as dopamine depletion and acetylcholinesterase inhibition. The anti-inflammatory properties of phytosterols involve the production of anti-inflammatory cytokines, the decrease in inflammatory mediator release, and the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Stigmasterol exerts anti-diabetic effects by reducing fasting glucose, serum insulin levels, and oral glucose tolerance. Other findings showed the antiparasitic activities of this molecule against certain strains of parasites such as Trypanosoma congolense (in vivo) and on promastigotes and amastigotes of the Leishmania major (in vitro). Some stigmasterol-rich plants were able to inhibit Candida albicans, virusei, and tropicalis at low doses. Accordingly, this review outlines key insights into the pharmacological abilities of stigmasterol and the specific mechanisms of action underlying some of these effects. Additionally, further investigation regarding pharmacodynamics, pharmacokinetics, and toxicology is recommended.
TL;DR: Overall, most available studies demonstrate that UCPs, particularly UCP2/3, prevent oxidative stress, however, the mechanism utilized to do so remains elusive and raises the question of UCP 2/3 should be renamed, since they may still not be true “uncoupling proteins”.
Abstract: Mitochondrial uncoupling proteins (UCP) 1-3 fulfill many physiological functions, ranging from non-shivering thermogenesis (UCP1) to glucose-stimulated insulin release (GSIS) and satiety signaling (UCP2) and muscle fuel metabolism (UCP3). Several studies have suggested that UCPs mediate these functions by facilitating proton return to the matrix. This would decrease protonic backpressure on the respiratory chain, lowering the production of hydrogen peroxide (H2O2), a second messenger. However, controlling mitochondrial H2O2 production to prevent oxidative stress by activating these leaks through these proteins is still enthusiastically debated. This is due to compelling evidence that UCP2/3 fulfill other function(s) and the inability to reproduce findings that UCP1-3 use inducible leaks to control reactive oxygen species (ROS) production. Further, other studies have found that UCP2/3 may serve as Ca2+. Therefore, we performed a systematic review aiming to summarize the results collected on the topic. A literature search using a list of curated keywords in Pubmed, BIOSIS Citation Index and Scopus was conducted. Potentially relevant references were screened, duplicate references eliminated, and then literature titles and abstracts were evaluated using Rayyan software. A total of 1101 eligible studies were identified for the review. From this total, 416 studies were evaluated based on our inclusion criteria. In general, most studies identified a role for UCPs in preventing oxidative stress, and in some cases, this may be related to the induction of leaks and lowering protonic backpressure on the respiratory chain. However, some studies also generated evidence that UCP2/3 may mitigate oxidative stress by transporting Ca2+ into the matrix, exporting lipid hydroperoxides, or by transporting C-4 metabolites. Additionally, some showed that activating UCP1 or 3 can increase mitochondrial ROS production, even though there is still augmented protection from oxidative stress. Conclusion: Overall, most available studies demonstrate that UCPs, particularly UCP2/3, prevent oxidative stress. However, the mechanism utilized to do so remains elusive and raises the question that UCP2/3 should be renamed, since they may still not be true “uncoupling proteins”.