Extracellular Vesicles in the Central Nervous System: A Novel Mechanism of Neuronal Cell Communication.

Cell-to-cell communication is essential for the appropriate development and maintenance of homeostatic conditions in the central nervous system. Extracellular vesicles have recently come to the forefront of neuroscience as novel vehicles for the transfer of complex signals between neuronal cells. Extracellular vesicles are membrane-bound carriers packed with proteins, metabolites, and nucleic acids (including DNA, mRNA, and microRNAs) that contain the elements present in the cell they originate from. Since their discovery, extracellular vesicles have been studied extensively and have opened up new understanding of cell-cell communication; they may cross the blood-brain barrier in a bidirectional way from the bloodstream to the brain parenchyma and vice versa, and play a key role in brain-periphery communication in physiology as well as pathology. Neurons and glial cells in the central nervous system release extracellular vesicles to the interstitial fluid of the brain and spinal cord parenchyma. Extracellular vesicles contain proteins, nucleic acids, lipids, carbohydrates, and primary and secondary metabolites. that can be taken up by and modulate the behaviour of neighbouring recipient cells. The functions of extracellular vesicles have been extensively studied in the context of neurodegenerative diseases. The purpose of this review is to analyse the role extracellular vesicles extracellular vesicles in central nervous system cell communication, with particular emphasis on the contribution of extracellular vesicles from different central nervous system cell types in maintaining or altering central nervous system homeostasis.

The Ketogenic Diet and Neuroinflammation: The Action of Beta-Hydroxybutyrate in a Microglial Cell Line.

The ketogenic diet (KD), a diet high in fat and protein but low in carbohydrates, is gaining much interest due to its positive effects, especially in neurodegenerative diseases. Beta-hydroxybutyrate (BHB), the major ketone body produced during the carbohydrate deprivation that occurs in KD, is assumed to have neuroprotective effects, although the molecular mechanisms responsible for these effects are still unclear. Microglial cell activation plays a key role in the development of neurodegenerative diseases, resulting in the production of several proinflammatory secondary metabolites. The following study aimed to investigate the mechanisms by which BHB determines the activation processes of BV2 microglial cells, such as polarization, cell migration and expression of pro- and anti-inflammatory cytokines, in the absence or in the presence of lipopolysaccharide (LPS) as a proinflammatory stimulus. The results showed that BHB has a neuroprotective effect in BV2 cells, inducing both microglial polarization towards an M2 anti-inflammatory phenotype and reducing migratory capacity following LPS stimulation. Furthermore, BHB significantly reduced expression levels of the proinflammatory cytokine IL-17 and increased levels of the anti-inflammatory cytokine IL-10. From this study, it can be concluded that BHB, and consequently the KD, has a fundamental role in neuroprotection and prevention in neurodegenerative diseases, presenting new therapeutic targets.

Recent Progress in Understanding the Health Benefits of Curcumin.

Nutrients and their potential benefits are a new field of study in modern medicine due to their positive impact on health [...].

The Effects of Curcumin on Inflammasome: Latest Update.

Curcumin, a traditional Chinese medicine extracted from natural plant rhizomes, has become a candidate drug for the treatment of different diseases due to its anti-inflammatory, anticancer, antioxidant, and antibacterial activities. Curcumin is generally beneficial to improve human health with anti-inflammatory and antioxidative properties as well as antitumor and immunoregulatory properties. Inflammasomes are NLR family, pyrin domain-containing 3 (NLRP3) proteins that are activated in response to a variety of stress signals and that promote the proteolytic conversion of pro-interleukin-1ß and pro-interleukin-18 into active forms, which are central mediators of the inflammatory response; inflammasomes can also induce pyroptosis, a type of cell death. The NLRP3 protein is involved in a variety of inflammatory pathologies, including neurological and autoimmune disorders, lung diseases, atherosclerosis, myocardial infarction, and many others. Different functional foods may have preventive and therapeutic effects in a wide range of pathologies in which inflammasome proteins are activated. In this review, we have focused on curcumin and evidenced its therapeutic potential in inflammatory diseases such as neurodegenerative diseases, respiratory diseases, and arthritis by acting on the inflammasome.

α-Tocopherol Protects Lipopolysaccharide-Activated BV2 Microglia.

Microglia, the resident macrophage-like population in the central nervous system, play a crucial role in the pathogenesis of many neurodegenerative disorders by triggering an inflammatory response that leads to neuronal death. Neuroprotective compounds to treat or prevent neurodegenerative diseases are a new field of study in modern medicine. Microglia are activated in response to inflammatory stimuli. The pathogenesis of various neurodegenerative diseases is closely related to the constant activation of microglia due to their fundamental role as a mediator of inflammation in the brain environment. α-Tocopherol, also known as vitamin E, is reported to possess potent neuroprotective effects. The goal of this study was to investigate the biological effects of vitamin E on BV2 microglial cells, as a possible neuroprotective and anti-inflammatory agent, following stimulation with lipopolysaccharide (LPS). The results showed that the pre-incubation of microglia with α-tocopherol can guarantee neuroprotective effects during microglial activation induced by LPS. α-Tocopherol preserved the branched morphology typical of microglia in a physiological state. It also reduced the migratory capacity; the production of pro-inflammatory and anti-inflammatory cytokines such as TNF-α and IL-10; and the activation of receptors such as TRL4 and CD40, which modulate the PI3K-Akt signaling pathway. The results of this study require further insights and research, but they present new scenarios for the application of vitamin E as an antioxidant for the purpose of greater neuroprotection in vivo for the prevention of possible neurodegenerative diseases.

Neurodegenerative Diseases: Can Caffeine Be a Powerful Ally to Weaken Neuroinflammation?

In recent years, there has been considerable research showing that coffee consumption seems to be beneficial to human health, as it contains a mixture of different bioactive compounds such as chlorogenic acids, caffeic acid, alkaloids, diterpenes and polyphenols. Neurodegenerative diseases (NDs) are debilitating, and non-curable diseases associated with impaired central, peripheral and muscle nervous systems. Several studies demonstrate that neuroinflammation mediated by glial cells-such as microglia and astrocytes-is a critical factor contributing to neurodegeneration that causes the dysfunction of brain homeostasis, resulting in a progressive loss of structure, function, and number of neuronal cells. This happens over time and leads to brain damage and physical impairment. The most known chronic NDs are represented by Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD). According to epidemiological studies, regular coffee consumption is associated with a lower risk of neurodegenerative diseases. In this review, we summarize the latest research about the potential effects of caffeine in neurodegenerative disorders prevention and discuss the role of controlled caffeine delivery systems in maintaining high plasma caffeine concentrations for an extended time.

Inflammaging and Brain: Curcumin and Its Beneficial Potential as Regulator of Microglia Activation.

Inflammaging is a term used to describe the tight relationship between low-grade chronic inflammation and aging that occurs during physiological aging in the absence of evident infection. This condition has been linked to a broad spectrum of age-related disorders in various organs including the brain. Inflammaging represents a highly significant risk factor for the development and progression of age-related conditions, including neurodegenerative diseases which are characterized by the progressive dysfunction and degeneration of neurons in the brain and peripheral nervous system. Curcumin is a widely studied polyphenol isolated from Curcuma longa with a variety of pharmacologic properties. It is well-known for its healing properties and has been extensively used in Asian medicine to treat a variety of illness conditions. The number of studies that suggest beneficial effects of curcumin on brain pathologies and age-related diseases is increasing. Curcumin is able to inhibit the formation of reactive-oxygen species and other pro-inflammatory mediators that are believed to play a pivotal role in many age-related diseases. Curcumin has been recently proposed as a potential useful remedy against neurodegenerative disorders and brain ageing. In light of this, our current review aims to discuss the potential positive effects of Curcumin on the possibility to control inflammaging emphasizing the possible modulation of inflammaging processes in neurodegenerative diseases.

Functional Role of Non-Muscle Myosin II in Microglia: An Updated Review.

Myosins are a remarkable superfamily of actin-based motor proteins that use the energy derived from ATP hydrolysis to translocate actin filaments and to produce force. Myosins are abundant in different types of tissues and involved in a large variety of cellular functions. Several classes of the myosin superfamily are expressed in the nervous system; among them, non-muscle myosin II (NM II) is expressed in both neurons and non-neuronal brain cells, such as astrocytes, oligodendrocytes, endothelial cells, and microglia. In the nervous system, NM II modulates a variety of functions, such as vesicle transport, phagocytosis, cell migration, cell adhesion and morphology, secretion, transcription, and cytokinesis, as well as playing key roles during brain development, inflammation, repair, and myelination functions. In this review, we will provide a brief overview of recent emerging roles of NM II in resting and activated microglia cells, the principal regulators of immune processes in the central nervous system (CNS) in both physiological and pathological conditions. When stimulated, microglial cells react and produce a number of mediators, such as pro-inflammatory cytokines, free radicals, and nitric oxide, that enhance inflammation and contribute to neurodegenerative diseases. Inhibition of NM II could be a new therapeutic target to treat or to prevent CNS diseases.

New Promising Therapeutic Avenues of Curcumin in Brain Diseases.

Curcumin, the dietary polyphenol isolated from Curcuma longa (turmeric), is commonly used as an herb and spice worldwide. Because of its bio-pharmacological effects curcumin is also called "spice of life", in fact it is recognized that curcumin possesses important proprieties such as anti-oxidant, anti-inflammatory, anti-microbial, antiproliferative, anti-tumoral, and anti-aging. Neurodegenerative diseases such as Alzheimer's Diseases, Parkinson's Diseases, and Multiple Sclerosis are a group of diseases characterized by a progressive loss of brain structure and function due to neuronal death; at present there is no effective treatment to cure these diseases. The protective effect of curcumin against some neurodegenerative diseases has been proven by in vivo and in vitro studies. The current review highlights the latest findings on the neuroprotective effects of curcumin, its bioavailability, its mechanism of action and its possible application for the prevention or treatment of neurodegenerative disorders.

Curcumin as Prospective Anti-Aging Natural Compound: Focus on Brain.

The nutrients and their potential benefits are a new field of study in modern medicine for their positive impact on health. Curcumin, the yellow polyphenolic compound extracted from Curcuma longa species, is widely used in traditional Ayurvedic medicine to prevent and contrast many diseases, considering its antioxidant, immunomodulatory, anti-inflammatory, anti-microbial, cardio-protective, nephron-protective, hepato-protective, anti-neoplastic, and anti-rheumatic proprieties. In recent years, the investigations of curcumin have been focused on its application to aging and age-associated diseases. Aging is a physiological process in which there is a decreasing of cellular function due to internal or external stimuli. Oxidative stress is one of the most important causes of aging and age-related diseases. Moreover, many age-related disorders such as cancer, neuroinflammation, and infections are due to a low-grade chronic systemic inflammation. Curcumin acting on different proteins is able to contrast both oxidative stress than inflammation. In the brain, curcumin is able to modulate inflammation induced by microglia. Finally in brain tumors curcumin is able to reduce tumor growth by inhibition of telomerase activity. This review emphasizes the anti-aging role of curcumin focusing on its mechanism to counteract aging in the brain. Moreover, new formulations to increase the bioavailability of curcumin are discussed.

The Emerging Role of Curcumin in the Modulation of TLR-4 Signaling Pathway: Focus on Neuroprotective and Anti-Rheumatic Properties.

Natural products have been used in medicine for thousands of years. Given their potential health benefits, they have gained significant popularity in recent times. The administration of phytochemicals existed shown to regulate differential gene expression and modulate various cellular pathways implicated in cell protection. Curcumin is a natural dietary polyphenol extracted from Curcuma Longa Linn with different biological and pharmacological effects. One of the important targets of curcumin is Toll-like receptor-4 (TLR-4), the receptor which plays a key role in the modulation of the immune responses and the stimulation of inflammatory chemokines and cytokines production. Different studies have demonstrated that curcumin attenuates inflammatory response via TLR-4 acting directly on receptor, or by its downstream pathway. Curcumin bioavailability is low, so the use of exosomes, as nano drug delivery, could improve the efficacy of curcumin in inflammatory diseases. The focus of this review is to explore the therapeutic effect of curcumin interacting with TLR-4 receptor and how this modulation could improve the prognosis of neuroinflammatory and rheumatic diseases.

The multiple roles of exosomes in Parkinson's disease: an overview.

The extracellular vesicles (EVs) represent a relatively new field of research in neurodegenerative disease and they are thought to be one of the ways that neurodegenerative pathologies, such as Parkinson's Disease (PD), spread in the brain. EVs are membrane vesicles released from cells into the extracellular space and they are produced by all cells of the nervous tissue. The classification of the vesicle subtypes comprises exosomes, microvesicles/microparticles, apoptotic bodies. EVs change in number and content in response to environmental conditions and may function as shuttles for the delivery of cargo between cells. Recent data suggest that exosomes secreted by both activated microglia and neurons play an important role in α-synuclein (α-syn) spreading and increase of neuroinflammation, thus exacerbating neuronal dysfunction and disease progression. α-syn is a presynaptic protein secreted by neurons in small amounts, and it is the main component of Lewy bodies, one of the histopathological features of PD. Several factors have shown to induce and/or modulate α-syn structure and oligomerization in vitro. Under pathological conditions, progressive accumulation of α-syn and the formation of oligomers have been proposed to play a critical role in the pathogenesis of PD. This review gives an overview about the multiple roles of exosomes in PD, despite their role in the progression of neurodegeneration, exosomes could represent a specific drug delivery tool for a difficult target such as the brain, which poses an obstacle to most drugs and they could also represent new biomarkers to track the progression of PD.

Folic Acid Is Able to Polarize the Inflammatory Response in LPS Activated Microglia by Regulating Multiple Signaling Pathways.

We investigated the ability of folic acid to modulate the inflammatory responses of LPS activated BV-2 microglia cells and the signal transduction pathways involved. To this aim, the BV-2 cell line was exposed to LPS as a proinflammatory response inducer, in presence or absence of various concentrations of folic acid. The production of nitric oxide (NO) was determined by the Griess test. The levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), and IL-10 were determined by ELISA. Inducible NO synthase (iNOS), nuclear transcription factor-kappa B (NF-κB) p65, MAPKs protein, and suppressors of cytokine signaling (SOCS)1 and SOCS3 were analyzed by western blotting. TNF-α and IL-1ß, as well as iNOS dependent NO production, resulted significantly inhibited by folic acid pretreatment in LPS-activated BV-2 cells. We also observed that folic acid dose-dependently upregulated both SOCS1 and SOCS3 expression in BV-2 cells, leading to an increased expression of the anti-inflammatory cytokine IL-10. Finally, p-IκBα, which indirectly reflects NF-κB complex activation, and JNK phosphorylation resulted dose-dependently downregulated by folic acid pretreatment of LPS-activated cells, whereas p38 MAPK phosphorylation resulted significantly upregulated by folic acid treatment. Overall, these results demonstrated that folic acid was able to modulate the inflammatory response in microglia cells, shifting proinflammatory versus anti-inflammatory responses through regulating multiple signaling pathways.

Selective cyclooxygenase-1 inhibition by p6 and gastrotoxicity: preliminary investigation.

BACKGROUND/AIMS: Gastrointestinal damage (GD) is commonly associated with the inhibition of cyclooxygenase (COX)-1, one of the two known COXs, by traditional non-steroidal anti-inflammatory drugs. More recent evidences have proven that GD is caused by the simultaneous inhibition of the two COXs. This study was designed to evaluate the effect of the selective COX-1 inhibition on gastric integrity. METHODS: GD was evaluated in male CD1 mice. Drugs were administered by gastric gavage at a dose of 50 mg/kg (injection volume of 100 µl). Control mice received an equal volume of the vehicle (10% ethanol). Each mouse, in groups of at least 6 mice, received one dose/day for 5 days. RESULTS: In Western blot analysis, COX-1 expression levels were found to be significantly reduced in mice treated with 3-(5-chlorofuran-2-yl)-5-methyl-4-phenylisoxazole (P6) in comparison to mice pretreated with aspirin (ASA), which exhibited higher levels of COX-1, thus confirming the high selectivity of P6 towards COX-1 enzyme inhibition. Mucosal sections obtained from ASA-treated mice showed breaks in the epithelial barrier and a marked alteration of foveolae and gastric glands, whereas stomachs isolated from mice sacrificed after 5 days of chronic administration of P6 (at a dose of up to 50 mg/kg/day) showed sporadic transient mucosal hyperemia and did not seem to display any significant gastric damage. CONCLUSIONS: The selective COX-1 inhibition by P6 does not cause gastric damage in mice but preserves mucosal integrity.

Inflammatory Skin Diseases: Focus on the Role of Suppressors of Cytokine Signaling (SOCS) Proteins.

Inflammatory skin diseases include a series of disorders characterized by a strong activation of the innate and adaptive immune system in which proinflammatory cytokines play a fundamental role in supporting inflammation. Skin inflammation is a complex process influenced by various factors, including genetic and environmental factors, characterized by the dysfunction of both immune and non-immune cells. Psoriasis (PS) and atopic dermatitis (AD) are the most common chronic inflammatory conditions of the skin whose pathogeneses are very complex and multifactorial. Both diseases are characterized by an immunological dysfunction involving a predominance of Th1 and Th17 cells in PS and of Th2 cells in AD. Suppressor of cytokine signaling (SOCS) proteins are intracellular proteins that control inflammatory responses by regulating various signaling pathways activated by proinflammatory cytokines. SOCS signaling is involved in the regulation and progression of inflammatory responses in skin-resident and non-resident immune cells, and recent data suggest that these negative modulators are dysregulated in inflammatory skin diseases such as PS and AD. This review focuses on the current understanding about the role of SOCS proteins in modulating the activity of inflammatory mediators implicated in the pathogenesis of inflammatory skin diseases such as PS and AD.

Functional and Therapeutic Potential of Cynara scolymus in Health Benefits.

Dietary supplements enriched with bioactive compounds represent a promising approach to influence physiological processes and enhance longevity and overall health. Cynara cardunculus var. scolymus serves as a functional food supplement with a high concentration of bioactive compounds, which offers various health-promoting benefits. Several chronic diseases have metabolic, genetic, or inflammatory origins, which are frequently interconnected. Pharmacological treatments, although effective, often result in undesirable side effects. In this context, preventive approaches are gaining increased attention. Recent literature indicates that the consumption of bioactive compounds in the diet can positively influence the organism's biological functions. Polyphenols, well-known for their health benefits, are widely recognized as valuable compounds in preventing/combating various pathologies related to lifestyle, metabolism, and aging. The C. scolymus belonging to the Asteraceae family, is widely used in the food and herbal medicine fields for its beneficial properties. Although the inflorescences (capitula) of the artichoke are used for food and culinary purposes, preparations based on artichoke leaves can be used as an active ingredient in herbal medicines. Cynara scolymus shows potential benefits in different domains. Its nutritional value and health benefits make it a promising candidate for improving overall well-being. C. scolymus exhibits anti-inflammatory, antioxidant, liver-protective, bile-expelling, antimicrobial, and lipid-lowering neuroprotective properties. Different studies demonstrate that oxidative stress is the leading cause of the onset and progression of major human health disorders such as cardiovascular, neurological, metabolic, and cancer diseases. The large amount of polyphenol found in C. scolymus has an antioxidant activity, enabling it to neutralize free radicals, preventing cellular damage. This reduces the subsequent risk of developing conditions such as cancer, diabetes, and cardiovascular diseases. Additionally, these polyphenols demonstrate anti-inflammatory activity, which is closely associated with their antioxidant properties. As a result, C. scolymus has the potential to contribute to the treatment of chronic diseases, including intestinal disorders, cardiovascular diseases, and neurodegenerative pathologies. The current review discussed the nutritional profiles, potential benefits, and pharmacological effects of C. scolymus.

18F-FDG PET/CT in early phase of sporadic Creutzfeldt-Jacob disease: A case report.

Key Clinical Message: Creutzfeldt-Jakob disease is a neurodegenerative disorder caused by brain accumulation of a misfolded form of the cellular prion protein, whose diagnosis is challenging, particularly in early stages, due to the variability and nonspecificity of the clinical and radiological features. 18F-fluorodeoxyglucose positron-emitted tomography has the potential to be considered a crucial investigation in these patients, revealing metabolic abnormalities earlier than the conventional neuroimaging analysis. Abstract: A 59-year-old man, the military officer, was referred to our Units for the onset of neurological symptoms rapidly evolving within a month, characterized by akinetic mutism, constructional apraxia, and disorders of spatial orientation. Brain 18F-fluorodeoxyglucose (18F-FDG) positron-emitted tomography (PET)/CT depicted an asymmetric hypometabolism in the left fronto-temporo-parietal cortex, as well as in the left thalamus and the right cerebellar hemisphere, while the glucose metabolism appears to be preserved in the somatosensory cortex and the basal ganglia. Laboratory routine analyses, cerebrospinal fluid routine, infective tests, electroencephalography (EEG), and brain magnetic resonance (MR) were all unremarkable. A positive RT-QuIC result on cerebro-spinal fluid (CSF) was subsequently shown, without any pathogenic gene mutations and, therefore, the result was consistent with a diagnosis of sporadic Creutzfeld-Jacob disease. The clinical evolution was quickly unfavorable, and the patient died about 4 months after hospital admission. FDG PET/computed tomography (CT) has the potential to be considered a crucial investigation in these patients, documenting metabolic changes long time before other diagnostic investigations such as CSF, EEG, brain CT, and brain MR, thus suggesting a greater sensitivity of glucose metabolic evaluation in the early stage of the disease in question.

Ser9p-GSK3ß Modulation Contributes to the Protective Effects of Vitamin C in Neuroinflammation.

BACKGROUND: The prolonged activation of microglia and excessive production of pro-inflammatory cytokines can lead to chronic neuroinflammation, which is an important pathological feature of Parkinson's disease (PD). We have previously reported the protective effect of Vitamin C (Vit C) on a mouse model of PD. However, its effect on microglial functions in neuroinflammation remains to be clarified. Glycogen synthase kinase 3ß (GSK3ß) is a serine/threonine kinase having a role in driving inflammatory responses, making GSK3ß inhibitors a promising target for anti-inflammatory research. METHODS: In this study, we investigated the possible involvement of GSK3ß in Vit C neuroprotective effects by using a well-known 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of PD and a cellular model of neuroinflammation, represented by Lipopolysaccharide (LPS)-activated BV-2 microglial cells. RESULTS: We demonstrated the ability of Vit C to decrease the expression of different mediators involved in the inflammatory responses, such as TLR4, p-IKBα, and the phosphorylated forms of p38 and AKT. In addition, we demonstrated for the first time that Vit C promotes the GSK3ß inhibition by stimulating its phosphorylation at Ser9. CONCLUSION: This study evidenced that Vit C exerts an anti-inflammatory function in microglia, promoting the upregulation of the M2 phenotype through the activation of the Wnt/ß-catenin signaling pathway.

Decoy Receptors Regulation by Resveratrol in Lipopolysaccharide-Activated Microglia.

Resveratrol is a polyphenol that acts as antioxidants do, protecting the body against diseases, such as diabetes, cancer, heart disease, and neurodegenerative disorders, such as Alzheimer's (AD) and Parkinson's diseases (PD). In the present study, we report that the treatment of activated microglia with resveratrol after prolonged exposure to lipopolysaccharide is not only able to modulate pro-inflammatory responses, but it also up-regulates the expression of decoy receptors, IL-1R2 and ACKR2 (atypical chemokine receptors), also known as negative regulatory receptors, which are able to reduce the functional responses promoting the resolution of inflammation. This result might constitute a hitherto unknown anti-inflammatory mechanism exerted by resveratrol on activated microglia.

Emerging Paradigms in Inflammatory Disease Management: Exploring Bioactive Compounds and the Gut Microbiota.

The human gut microbiota is a complex ecosystem of mutualistic microorganisms that play a critical role in maintaining human health through their individual interactions and with the host. The normal gastrointestinal microbiota plays a specific physiological function in host immunomodulation, nutrient metabolism, vitamin synthesis, xenobiotic and drug metabolism, maintenance of structural and functional integrity of the gut mucosal barrier, and protection against various pathogens. Inflammation is the innate immune response of living tissues to injury and damage caused by infections, physical and chemical trauma, immunological factors, and genetic derangements. Most diseases are associated with an underlying inflammatory process, with inflammation mediated through the contribution of active immune cells. Current strategies to control inflammatory pathways include pharmaceutical drugs, lifestyle, and dietary changes. However, this remains insufficient. Bioactive compounds (BCs) are nutritional constituents found in small quantities in food and plant extracts that provide numerous health benefits beyond their nutritional value. BCs are known for their antioxidant, antimicrobial, anticarcinogenic, anti-metabolic syndrome, and anti-inflammatory properties. Bioactive compounds have been shown to reduce the destructive effect of inflammation on tissues by inhibiting or modulating the effects of inflammatory mediators, offering hope for patients suffering from chronic inflammatory disorders like atherosclerosis, arthritis, inflammatory bowel diseases, and neurodegenerative diseases. The aim of the present review is to summarise the role of natural bioactive compounds in modulating inflammation and protecting human health, for their safety to preserve gut microbiota and improve their physiology and behaviour.