Search Results (9,839)

Recent evidence suggests that diet modifies key biological factors associated with the development of depression. It has been suggested that this could be due to the high flavonoid content commonly found in many plant foods, beverages and dietary supplements. Our aim was to conduct a systematic review to evaluate the effects of dietary flavonoids on the symptoms of depression. A total of 46 studies met the eligibility criteria. Of these, 36 were intervention trials and 10 were observational studies. A meta-analysis of 36 clinical trials involving a total of 2788 participants was performed. The results showed a statistically significant effect of flavonoids on depressive symptoms (mean difference = −1.65; 95% C.I., −2.54, −0.77; p < 0.01). Five of the 10 observational studies included in the systematic review reported significant results, suggesting that a higher flavonoid intake may improve symptoms of depression. Further studies are urgently required to elucidate whether causal and mechanistic links exist, along with substantiation of functional brain changes associated with flavonoid consumption. Full article

The role of mitochondrial function in health and disease has become increasingly recognized, particularly in the last two decades. Mitochondrial dysfunction as well as disruptions of cellular bioenergetics have been shown to be ubiquitous in some of the most prevalent diseases in our society, such as type 2 diabetes, cardiovascular disease, metabolic syndrome, cancer, and Alzheimer’s disease. However, the etiology and pathogenesis of mitochondrial dysfunction in multiple diseases have yet to be elucidated, making it one of the most significant medical challenges in our history. However, the rapid advances in our knowledge of cellular metabolism coupled with the novel understanding at the molecular and genetic levels show tremendous promise to one day elucidate the mysteries of this ancient organelle in order to treat it therapeutically when needed. Mitochondrial DNA mutations, infections, aging, and a lack of physical activity have been identified to be major players in mitochondrial dysfunction in multiple diseases. This review examines the complexities of mitochondrial function, whose ancient incorporation into eukaryotic cells for energy purposes was key for the survival and creation of new species. Among these complexities, the tightly intertwined bioenergetics derived from the combustion of alimentary substrates and oxygen are necessary for cellular homeostasis, including the production of reactive oxygen species. This review discusses different etiological mechanisms by which mitochondria could become dysregulated, determining the fate of multiple tissues and organs and being a protagonist in the pathogenesis of many non–communicable diseases. Finally, physical activity is a canonical evolutionary characteristic of humans that remains embedded in our genes. The normalization of a lack of physical activity in our modern society has led to the perception that exercise is an “intervention”. However, physical activity remains the modus vivendi engrained in our genes and being sedentary has been the real intervention and collateral effect of modern societies. It is well known that a lack of physical activity leads to mitochondrial dysfunction and, hence, it probably becomes a major etiological factor of many non–communicable diseases affecting modern societies. Since physical activity remains the only stimulus we know that can improve and maintain mitochondrial function, a significant emphasis on exercise promotion should be imperative in order to prevent multiple diseases. Finally, in populations with chronic diseases where mitochondrial dysfunction is involved, an individualized exercise prescription should be crucial for the “metabolic rehabilitation” of many patients. From lessons learned from elite athletes (the perfect human machines), it is possible to translate and apply multiple concepts to the betterment of populations with chronic diseases. Full article

According to our hypothesis, delayed onset muscle soreness (DOMS) is an acute compression axonopathy of the nerve endings in the muscle spindle. It is caused by the superposition of compression when repetitive eccentric contractions are executed under cognitive demand. The acute compression axonopathy could coincide with microinjury of the surrounding tissues and is enhanced by immune-mediated inflammation. DOMS is masked by sympathetic nervous system activity at initiation, but once it subsides, a safety mode comes into play to prevent further injury. DOMS becomes manifest when the microinjured non-nociceptive sensory fibers of the muscle spindle stop inhibiting the effects of the microinjured, hyperexcited nociceptive sensory fibers, therefore providing the ‘open gate’ in the dorsal horn to hyperalgesia. Reactive oxygen species and nitric oxide play a cross-talking role in the parallel, interlinked degeneration–regeneration mechanisms of these injured tissues. We propose that the mitochondrial electron transport chain generated free radical involvement in the acute compression axonopathy. ‘Closed gate exercises’ could be of nonpharmacological therapeutic importance, because they reduce neuropathic pain in addition to having an anti-inflammatory effect. Finally, DOMS could have an important ontogenetical role by not just enhancing ability to escape danger to survive in the wild, but also triggering muscle growth. Full article

Cannabidiol (CBD) is one of the main pharmacologically active phytocannabinoids of Cannabis sativa L. CBD is non-psychoactive but exerts a number of beneficial pharmacological effects, including anti-inflammatory and antioxidant properties. The chemistry and pharmacology of CBD, as well as various molecular targets, including cannabinoid receptors and other components of the endocannabinoid system with which it interacts, have been extensively studied. In addition, preclinical and clinical studies have contributed to our understanding of the therapeutic potential of CBD for many diseases, including diseases associated with oxidative stress. Here, we review the main biological effects of CBD, and its synthetic derivatives, focusing on the cellular, antioxidant, and anti-inflammatory properties of CBD. Full article

N-acetylcysteine (NAC) is a medicine widely used to treat paracetamol overdose and as a mucolytic compound. It has a well-established safety profile, and its toxicity is uncommon and dependent on the route of administration and high dosages. Its remarkable antioxidant and anti-inflammatory capacity is the biochemical basis used to treat several diseases related to oxidative stress and inflammation. The primary role of NAC as an antioxidant stems from its ability to increase the intracellular concentration of glutathione (GSH), which is the most crucial biothiol responsible for cellular redox imbalance. As an anti-inflammatory compound, NAC can reduce levels of tumor necrosis factor-alpha (TNF-α) and interleukins (IL-6 and IL-1β) by suppressing the activity of nuclear factor kappa B (NF-κB). Despite NAC’s relevant therapeutic potential, in several experimental studies, its effectiveness in clinical trials, addressing different pathological conditions, is still limited. Thus, the purpose of this chapter is to provide an overview of the medicinal effects and applications of NAC to human health based on current therapeutic evidence. Full article

Biomolecular condensates are membraneless organelles (MLOs) that form dynamic, chemically distinct subcellular compartments organizing macromolecules such as proteins, RNA, and DNA in unicellular prokaryotic bacteria and complex eukaryotic cells. Separated from surrounding environments, MLOs in the nucleoplasm, cytoplasm, and mitochondria assemble by liquid–liquid phase separation (LLPS) into transient, non-static, liquid-like droplets that regulate essential molecular functions. LLPS is primarily controlled by post-translational modifications (PTMs) that fine-tune the balance between attractive and repulsive charge states and/or binding motifs of proteins. Aberrant phase separation due to dysregulated membrane lipid rafts and/or PTMs, as well as the absence of adequate hydrotropic small molecules such as ATP, or the presence of specific RNA proteins can cause pathological protein aggregation in neurodegenerative disorders. Melatonin may exert a dominant influence over phase separation in biomolecular condensates by optimizing membrane and MLO interdependent reactions through stabilizing lipid raft domains, reducing line tension, and maintaining negative membrane curvature and fluidity. As a potent antioxidant, melatonin protects cardiolipin and other membrane lipids from peroxidation cascades, supporting protein trafficking, signaling, ion channel activities, and ATPase functionality during condensate coacervation or dissolution. Melatonin may even control condensate LLPS through PTM and balance mRNA- and RNA-binding protein composition by regulating N⁶-methyladenosine (m⁶A) modifications. There is currently a lack of pharmaceuticals targeting neurodegenerative disorders via the regulation of phase separation. The potential of melatonin in the modulation of biomolecular condensate in the attenuation of aberrant condensate aggregation in neurodegenerative disorders is discussed in this review. Full article

The ketogenic diet, originally developed for the treatment of epilepsy in non-responder children, is spreading to be used in the treatment of many diseases, including Alzheimer’s disease. The main activity of the ketogenic diet has been related to improved mitochondrial function and decreased oxidative stress. B-Hydroxybutyrate, the most studied ketone body, has been shown to reduce the production of reactive oxygen species (ROS), improving mitochondrial respiration: it stimulates the cellular endogenous antioxidant system with the activation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2), it modulates the ratio between the oxidized and reduced forms of nicotinamide adenine dinucleotide (NAD⁺/NADH) and it increases the efficiency of electron transport chain through the expression of uncoupling proteins. Furthermore, the ketogenic diet performs anti-inflammatory activity by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome as well as inhibiting histone deacetylases (HDACs), improving memory encoding. The underlying mechanisms and the perspectives for the treatment of Alzheimer’s disease are discussed. Full article

Global climate change and associated adverse abiotic stress conditions, such as drought, salinity, heavy metals, waterlogging, extreme temperatures, oxygen deprivation, etc., greatly influence plant growth and development, ultimately affecting crop yield and quality, as well as agricultural sustainability in general. Plant cells produce oxygen radicals and their derivatives, so-called reactive oxygen species (ROS), during various processes associated with abiotic stress. Moreover, the generation of ROS is a fundamental process in higher plants and employs to transmit cellular signaling information in response to the changing environmental conditions. One of the most crucial consequences of abiotic stress is the disturbance of the equilibrium between the generation of ROS and antioxidant defense systems triggering the excessive accumulation of ROS and inducing oxidative stress in plants. Notably, the equilibrium between the detoxification and generation of ROS is maintained by both enzymatic and nonenzymatic antioxidant defense systems under harsh environmental stresses. Although this field of research has attracted massive interest, it largely remains unexplored, and our understanding of ROS signaling remains poorly understood. In this review, we have documented the recent advancement illustrating the harmful effects of ROS, antioxidant defense system involved in ROS detoxification under different abiotic stresses, and molecular cross-talk with other important signal molecules such as reactive nitrogen, sulfur, and carbonyl species. In addition, state-of-the-art molecular approaches of ROS-mediated improvement in plant antioxidant defense during the acclimation process against abiotic stresses have also been discussed. Full article

Persea americana, commonly known as avocado, has recently gained substantial popularity and is often marketed as a “superfood” because of its unique nutritional composition, antioxidant content, and biochemical profile. However, the term “superfood” can be vague and misleading, as it is often associated with unrealistic health claims. This review draws a comprehensive summary and assessment of research performed in the last few decades to understand the nutritional and therapeutic properties of avocado and its bioactive compounds. In particular, studies reporting the major metabolites of avocado, their antioxidant as well as bioavailability and pharmacokinetic properties, are summarized and assessed. Furthermore, the potential of avocado in novel drug discovery for the prevention and treatment of cancer, microbial, inflammatory, diabetes, and cardiovascular diseases is highlighted. This review also proposes several interesting future directions for avocado research. Full article

Meat and meat products are a fundamental part of the human diet. The protein and vitamin content, as well as essential fatty acids, gives them an appropriate composition to complete the nutritional requirements. However, meat constituents are susceptible to degradation processes. Among them, the most important, after microbial deterioration, are oxidative processes, which affect lipids, pigments, proteins and vitamins. During these reactions a sensory degradation of the product occurs, causing consumer rejection. In addition, there is a nutritional loss that leads to the formation of toxic substances, so the control of oxidative processes is of vital importance for the meat industry. Nonetheless, despite lipid oxidation being widely investigated for decades, the complex reactions involved in the process, as well as the different pathways and factors that influenced them, make that lipid oxidation mechanisms have not yet been completely understood. Thus, this article reviews the fundamental mechanisms of lipid oxidation, the most important oxidative reactions, the main factors that influence lipid oxidation, and the routine methods to measure compounds derived from lipid oxidation in meat. Full article

Vitamin B3 (nicotinic acid, niacin) deficiency causes the systemic disease pellagra, which leads to dermatitis, diarrhea, dementia, and possibly death depending on its severity and duration. Vitamin B3 is used in the synthesis of the NAD⁺ family of coenzymes, contributing to cellular energy metabolism and defense systems. Although nicotinamide (niacinamide) is primarily used as a nutritional supplement for vitamin B3, its pharmaceutical and cosmeceutical uses have been extensively explored. In this review, we discuss the biological activities and cosmeceutical properties of nicotinamide in consideration of its metabolic pathways. Supplementation of nicotinamide restores cellular NAD⁺ pool and mitochondrial energetics, attenuates oxidative stress and inflammatory response, enhances extracellular matrix and skin barrier, and inhibits the pigmentation process in the skin. Topical treatment of nicotinamide, alone or in combination with other active ingredients, reduces the progression of skin aging and hyperpigmentation in clinical trials. Topically applied nicotinamide is well tolerated by the skin. Currently, there is no convincing evidence that nicotinamide has specific molecular targets for controlling skin aging and pigmentation. This substance is presumed to contribute to maintaining skin homeostasis by regulating the redox status of cells along with various metabolites produced from it. Thus, it is suggested that nicotinamide will be useful as a cosmeceutical ingredient to attenuate skin aging and hyperpigmentation, especially in the elderly or patients with reduced NAD⁺ pool in the skin due to internal or external stressors. Full article

Moringa Oleifera (MO), a plant from the family Moringacea is a major crop in Asia and Africa. MO has been studied for its health properties, attributed to the numerous bioactive components, including vitamins, phenolic acids, flavonoids, isothiocyanates, tannins and saponins, which are present in significant amounts in various components of the plant. Moringa Oleifera leaves are the most widely studied and they have shown to be beneficial in several chronic conditions, including hypercholesterolemia, high blood pressure, diabetes, insulin resistance, non-alcoholic liver disease, cancer and overall inflammation. In this review, we present information on the beneficial results that have been reported on the prevention and alleviation of these chronic conditions in various animal models and in cell studies. The existing limited information on human studies and Moringa Oleifera leaves is also presented. Overall, it has been well documented that Moringa Oleifera leaves are a good strategic for various conditions associated with heart disease, diabetes, cancer and fatty liver. Full article

The novel COVID-19 pandemic is affecting the world’s population differently: mostly in the presence of conditions such as aging, diabetes and hypertension the virus triggers a lethal cytokine storm and patients die from acute respiratory distress syndrome, whereas in many cases the disease has a mild or even asymptomatic progression. A common denominator in all conditions associated with COVID-19 appears to be the impaired redox homeostasis responsible for reactive oxygen species (ROS) accumulation; therefore, levels of glutathione (GSH), the key anti-oxidant guardian in all tissues, could be critical in extinguishing the exacerbated inflammation that triggers organ failure in COVID-19. The present review provides a biochemical investigation of the mechanisms leading to deadly inflammation in severe COVID-19, counterbalanced by GSH. The pathways competing for GSH are described to illustrate the events concurring to cause a depletion of endogenous GSH stocks. Drawing on evidence from literature that demonstrates the reduced levels of GSH in the main conditions clinically associated with severe disease, we highlight the relevance of restoring GSH levels in the attempt to protect the most vulnerable subjects from severe symptoms of COVID-19. Finally, we discuss the current data about the feasibility of increasing GSH levels, which could be used to prevent and subdue the disease. Full article

Melatonin, an indoleamine hormone produced and secreted at night by pinealocytes and extra-pineal cells, plays an important role in timing circadian rhythms (24-h internal clock) and regulating the sleep/wake cycle in humans. However, in recent years melatonin has gained much attention mainly because of its demonstrated powerful lipophilic antioxidant and free radical scavenging action. Melatonin has been proven to be twice as active as vitamin E, believed to be the most effective lipophilic antioxidant. Melatonin-induced signal transduction through melatonin receptors promotes the expression of antioxidant enzymes as well as inflammation-related genes. Melatonin also exerts an immunomodulatory action through the stimulation of high-affinity receptors expressed in immunocompetent cells. Here, we reviewed the efficacy, safety and side effects of melatonin supplementation in treating oxidative stress- and/or inflammation-related disorders, such as obesity, cardiovascular diseases, immune disorders, infectious diseases, cancer, neurodegenerative diseases, as well as osteoporosis and infertility. Full article

Oxidative stress is a metabolic dysfunction that favors the oxidation of biomolecules, contributing to the oxidative damage of cells and tissues. This consequently contributes to the development of several chronic diseases. In particular, zinc is one of the most relevant minerals to human health, because of its antioxidant properties. This review aims to provide updated information about the mechanisms involved in the protective role of zinc against oxidative stress. Zinc acts as a co-factor for important enzymes involved in the proper functioning of the antioxidant defense system. In addition, zinc protects cells against oxidative damage, acts in the stabilization of membranes and inhibits the enzyme nicotinamide adenine dinucleotide phosphate oxidase (NADPH-Oxidase). Zinc also induces the synthesis of metallothioneins, which are proteins effective in reducing hydroxyl radicals and sequestering reactive oxygen species (ROS) produced in stressful situations, such as in type 2 diabetes, obesity and cancer. Literature provides strong evidence for the role of zinc in the protection against oxidative stress in several diseases. Full article