The Immunomodulatory Effects of Sulforaphane in Exercise-Induced Inflammation and Oxidative Stress: A Prospective Nutraceutical.

Sulforaphane (SFN) is a promising molecule for developing phytopharmaceuticals due to its potential antioxidative and anti-inflammatory effects. A plethora of research conducted in vivo and in vitro reported the beneficial effects of SFN intervention and the underlying cellular mechanisms. Since SFN is a newly identified nutraceutical in sports nutrition, only some human studies have been conducted to reflect the effects of SFN intervention in exercise-induced inflammation and oxidative stress. In this review, we briefly discussed the effects of SFN on exercise-induced inflammation and oxidative stress. We discussed human and animal studies that are related to exercise intervention and mentioned the underlying cellular signaling mechanisms. Since SFN could be used as a potential therapeutic agent, we mentioned briefly its synergistic attributes with other potential nutraceuticals that are associated with acute and chronic inflammatory conditions. Given its health-promoting effects, SFN could be a prospective nutraceutical at the forefront of sports nutrition.

Sulforaphane Attenuates Neutrophil ROS Production, MPO Degranulation and Phagocytosis, but Does Not Affect NET Formation Ex Vivo and In Vitro.

Sulforaphane has several effects on the human body, including anti-inflammation, antioxidation, antimicrobial and anti-obesity effects. In this study, we examined the effect of sulforaphane on several neutrophil functions: reactive oxygen species (ROS) production, degranulation, phagocytosis, and neutrophil extracellular trap (NET) formation. We also examined the direct antioxidant effect of sulforaphane. First, we measured neutrophil ROS production induced by zymosan in whole blood in the presence of 0 to 560 µM sulforaphane. Second, we examined the direct antioxidant activity of sulforaphane using a HOCl removal test. In addition, inflammation-related proteins, including an azurophilic granule component, were measured by collecting supernatants following ROS measurements. Finally, neutrophils were isolated from blood, and phagocytosis and NET formation were measured. Sulforaphane reduced neutrophil ROS production in a concentration-dependent manner. The ability of sulforaphane to remove HOCl is stronger than that of ascorbic acid. Sulforaphane at 280 µM significantly reduced the release of myeloperoxidase from azurophilic granules, as well as that of the inflammatory cytokines TNF-α and IL-6. Sulforaphane also suppressed phagocytosis but did not affect NET formation. These results suggest that sulforaphane attenuates neutrophil ROS production, degranulation, and phagocytosis, but does not affect NET formation. Moreover, sulforaphane directly removes ROS, including HOCl.

The Potential of Exerkines in Women's COVID-19: A New Idea for a Better and More Accurate Understanding of the Mechanisms behind Physical Exercise.

The benefits of physical exercise are well-known, but there are still many questions regarding COVID-19. Chow et al.'s 2022 study, titled Exerkines and Disease, showed that a special focus on exerkines can help to better understand the underlying mechanisms of physical exercise and disease. Exerkines are a group of promising molecules that may underlie the beneficial effects of physical exercise in diseases. The idea of exerkines is to understand the effects of physical exercise on diseases better. Exerkines have a high potential for the treatment of diseases and, considering that, there is still no study of the importance of exerkines on the most dangerous disease in the world in recent years, COVID-19. This raises the fundamental question of whether exerkines have the potential to manage COVID-19. Most of the studies focused on the general changes in physical exercise in patients with COVID-19, both during the illness and after discharge from the hospital, and did not investigate the basic differences. A unique look at the management of COVID-19 by exerkines, especially in obese and overweight women who experience high severity of COVID-19 and whose recovery period is long after discharge from the hospital, can help to understand the basic mechanisms. In this review, we explore the potential of exerkines in COVID-19 by practicing physical exercise to provide compelling practice recommendations with new insights.

A Guide to Different Intensities of Exercise, Vaccination, and Sports Nutrition in the Course of Preparing Elite Athletes for the Management of Upper Respiratory Infections during the COVID-19 Pandemic: A Narrative Review.

Elite athletes use high-intensity training to maintain their fitness level. However, intense training can harm the immune system, making athletes suspectable to COVID-19 and negatively affecting their performance. In addition, the diet of athletes should be appreciated more as it is another influencer of the immune system, especially during the COVID 19 pandemic. The other important issue elite athletes face currently is vaccination and its possible intervention with their training. The present study attempts to discuss the impact of different training intensities, nutritional strategies, and vaccination on the immune system function in elite athletes. To this end, Scopus, ISC, PubMed, Web of Science, and Google Scholar databases were searched from 1988 to 2021 using the related keywords. The results of our review showed that although high-intensity exercise can suppress the immune system, elite athletes should not stop training in the time of infection but use low- and moderate-intensity training. Moderate-intensity exercise can improve immune function and maintain physical fitness. In addition, it is also better for athletes not to undertake high-intensity training at the time of vaccination, but instead perform moderate to low-intensity training. Furthermore, nutritional strategies can be employed to improve immune function during high-intensity training periods.

A Brief Overview of Oxidative Stress in Adipose Tissue with a Therapeutic Approach to Taking Antioxidant Supplements.

One of the leading causes of obesity associated with oxidative stress (OS) is excessive consumption of nutrients, especially fast-foods, and a sedentary lifestyle, characterized by the ample accumulation of lipid in adipose tissue (AT). When the body needs energy, the lipid is broken down into glycerol (G) and free fatty acids (FFA) during the lipolysis process and transferred to various tissues in the body. Materials secreted from AT, especially adipocytokines (interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α)) and reactive oxygen species (ROS), are impressive in causing inflammation and OS of AT. There are several ways to improve obesity, but researchers have highly regarded the use of antioxidant supplements due to their neutralizing properties in removing ROS. In this review, we have examined the AT response to OS to antioxidant supplements focusing on animal studies. The results are inconsistent due to differences in the study duration and diversity in animals (strain, age, and sex). Therefore, there is a need for different studies, especially in humans.

Physical activity and nutrition guidelines to help with the fight against COVID-19.

As the world is witnessing the epidemic of coronavirus disease 2019, emerging genetics and clinical pieces of evidence suggest a similar immunopathology to those of severe acute respiratory syndrome and Middle East respiratory syndrome. Staying at home to prevent the spread of the virus and consequently being largely inactive is associated with unintended consequences. These can actually enhance the infection risk and exacerbate poor health conditions including impaired immune function. Physical activity is a feasible way of improving health, particularly physical and mental health in a time of social isolation. However, people with certain health conditions in these circumstances may need a special physical activity programme in addition to any exercise they may already be performing via online programmes. This review aims to provide practical guidelines during the COVID-19 quarantine period. We suggest performing aerobic, resistance training, respiratory muscle training and yoga in the healthy, and in those with upper respiratory tract illness, patients with lower respiratory tract illness should be restricted to respiratory muscle training and yoga. In addition, vitamins D and C, omega-3 fatty acids, and regular consumption of fruit and vegetables might be considered as nutritional aids to support the immune system in those affected by COVID-19.

The Integrative Role of Sulforaphane in Preventing Inflammation, Oxidative Stress and Fatigue: A Review of a Potential Protective Phytochemical.

Cruciferous vegetables hold a myriad of bioactive molecules that are renowned for possessing unique medicinal benefits. Sulforaphane (SFN) is one of the potential nutraceuticals contained within cruciferous vegetables that is useful for improving health and diseased conditions. The objective of this review is to discuss the mechanistic role for SFN in preventing oxidative stress, fatigue, and inflammation. Direct and indirect research evidence is reported to identify the nontoxic dose of SFN for human trials, and effectiveness of SFN to attenuate inflammation and/or oxidative stress. SFN treatment modulates redox balance via activating redox regulator nuclear factor E2 factor-related factor (Nrf2). SFN may play a crucial role in altering the Keap1/Nrf2/ARE pathway (an intricate response to many stimuli or stress), which induces Nrf2 target gene activation to reduce oxidative stress. In addition, SFN reduces inflammation by suppressing centrally involved inflammatory regulator nuclear factor-kappa B (NF-κB), which in turn downregulates the expression of proinflammatory cytokines and mediators. Exercise may induce a significant range of fatigue, inflammation, oxidative stress, and/or organ damage due to producing excessive reactive oxygen species (ROS) and inflammatory cytokines. SFN may play an effective role in preventing such damage via inducing phase 2 enzymes, activating the Nrf2/ARE signaling pathway or suppressing nuclear translocation of NF-κB. In this review, we summarize the integrative role of SFN in preventing fatigue, inflammation, and oxidative stress, and briefly introduce the history of cruciferous vegetables and the bioavailability and pharmacokinetics of SFN reported in previous research. To date, very limited research has been conducted on SFN's effectiveness in improving exercise endurance or performance. Therefore, more research needs to be carried out to determine the effectiveness of SFN in the field of exercise and lifestyle factors.

Organosulfur Compounds: A Review of Their Anti-inflammatory Effects in Human Health.

Phytonutrients are widely recognized for providing protective human health benefits. Among the phytonutrients, epidemiological and experimental studies show that dietary organosulfur compounds (OSC) play a significant role in preventing various human pathological progressions, including chronic inflammation, by decreasing inflammatory mediators such as nitric oxide (NO), prostaglandin (PG)E2, interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and IL-17, which are all typical hallmarks of inflammation. Evidence supports OSC in reducing the expression of these markers, thereby attenuating chronic inflammatory processes. Nuclear factor-kappa B (NF-κB) is a key regulating factor during inflammation, and novel evidence shows that OSC downregulates this transcriptional factor, thus contributing to the anti-inflammatory response. In vitro and in vivo studies show that inflammation is mechanistically linked with acute and chronic pathological conditions including cancer, diabetes, obesity, neural dysfunction, etc. Furthermore, a considerable number of experiments have demonstrated that the anti-inflammatory properties of OSC occur in a dose-dependent manner. These experiments also highlight indirect mechanisms as well as potent co-functions for protective roles as antioxidants, and in providing chemoprotection and neuroprotection. In this brief review, we provided an overview of the anti-inflammatory effects of OSC and elucidated probable mechanisms that are associated with inflammation and chronic disorders.

Characterization and Modulation of Systemic Inflammatory Response to Exhaustive Exercise in Relation to Oxidative Stress.

Exhaustive exercise induces systemic inflammatory responses, which are associated with exercise-induced tissue/organ damage, but the sources and triggers are not fully understood. Herein, the basics of inflammatory mediator cytokines and research findings on the effects of exercise on systemic inflammation are introduced. Subsequently, the association between inflammatory responses and tissue damage is examined in exercised and overloaded skeletal muscle and other internal organs. Furthermore, an overview of the interactions between oxidative stress and inflammatory mediator cytokines is provided. Particularly, the transcriptional regulation of redox signaling and pro-inflammatory cytokines is described, as the activation of the master regulatory factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is involved directly or indirectly in controlling pro-inflammatory genes and antioxidant enzymes expression, whilst nuclear factor-kappa B (NF-κB) regulates the pro-inflammatory gene expression. Additionally, preventive countermeasures against the pathogenesis along with the possibility of interventions such as direct and indirect antioxidants and anti-inflammatory agents are described. The aim of this review is to give an overview of studies on the systematic inflammatory responses to exercise, including our own group as well as others. Moreover, the challenges and future directions in understanding the role of exercise and functional foods in relation to inflammation and oxidative stress are discussed.

Protective Effects of Sulforaphane on Exercise-Induced Organ Damage via Inducing Antioxidant Defense Responses.

Regular exercise is beneficial to maintain a healthy lifestyle, but the beneficial effects are lost in the case of acute exhaustive exercise; this causes significant inflammation, oxidative stress along with organ damage. Recently, sulforaphane (SFN), an indirect antioxidant, has drawn special attention for its potential protective effect against inflammation and oxidative stress. However, no studies have been performed regarding acute exhaustive exercise-induced organ damage in association with SFN administration. Therefore, the aim of this study was to investigate the effects of SFN on acute exhaustive exercise-induced organ damage and the mechanisms involved. To perform the study, we divided mice into four groups: Control, SFN, exercise, and SFN plus exercise. The SFN group was administered orally (50 mg/kg body wt) 2 h before the running test. We measured plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH), and acute exhaustive exercise significantly increased these biomarkers. In addition, the mRNA expression of pro-inflammatory cytokines, IL-6, IL-1ß, and TNF-α, were significantly increased in the liver of exercise group. However, the SFN plus exercise group showed a significant reduction in the expression of cytokines and blood biomarkers of tissue damage or cell death. Furthermore, we measured mRNA expression of Nrf2, heme oxygenase (HO)-1, and antioxidant defense enzymes expression, i.e., superoxide dismutase (SOD1), catalase (CAT), and glutathione peroxidase (GPx1) in the liver. The expression of all these biomarkers was significantly upregulated in the SFN plus exercise group. Collectively, SFN may protect the liver from exhaustive exercise-induced inflammation via inducing antioxidant defense response through the activation of Nrf2/HO-1 signal transduction pathway.

Sulforaphane Protects Cells against Lipopolysaccharide-Stimulated Inflammation in Murine Macrophages.

Inflammation is an essential part for the general or innate immune defenses to defend against tissue damage and accelerate the curing process by providing protection against pathogens. Sulforaphane (SFN) is a natural isothiocyanate that has potential properties against inflammation, along with other protective functions. The purpose of this study was to examine the mechanism of its protective effect on lipopolysaccharide (LPS)-induced inflammation in Raw 264.7 macrophages. Here, we compared LPS-challenged macrophages with or without SFN pretreatment. Macrophages were pre-incubated for 6 h with a wide range of concentrations of SFN (0 to 50 µM), and then treated with LPS for 24 h. Nitric oxide (NO) concentration and gene expression of different inflammatory mediators, i.e., interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1ß, were measured. SFN neither directly reacted with cytokines, nor with NO. To understand the mechanisms, we performed analyses of the expression of regulatory enzyme inducible nitic oxide synthase (iNOS), the transcription factor NF-E2-related factor 2 (Nrf2), and its enzyme heme-oxygenase (HO)-1. Our results revealed that LPS increased significantly the expression of inflammatory cytokines and concentration of NO in non-treated cells. SFN was able to prevent the expression of NO and cytokines through regulating inflammatory enzyme iNOS and activation of Nrf2/HO-1 signal transduction pathway.