curcumin and Nervous-System-Diseases

Aberrant neurogenesis is a major factor in psychiatric and neurological disorders that have significantly attracted the attention of neuroscientists. Curcumin is a primary constituent of curcuminoid that exerts several positive pharmacological effects on aberrant neurogenesis. First, it is important to understand the different processes of neurogenesis, and whether their dysfunction promotes etiology as well as the development of many psychiatric and neurological disorders; then investigate mechanisms by which curcumin affects neurogenesis as an active participant in pathophysiological events. Based on scientometric studies and additional extensive research, we explore the mechanisms by which curcumin regulates adult neurogenesis and in turn affects psychiatric diseases, i.e., depression and neurological disorders among them traumatic brain injury (TBI), stroke, Alzheimer's disease (AD), Gulf War Illness (GWI) and Fragile X syndrome (FXS). This review aims to elucidate the therapeutic effects and mechanisms of curcumin on adult neurogenesis in various psychiatric and neurological disorders. Specifically, we discuss the regulatory role of curcumin in different activities of neural stem cells (NSCs), including proliferation, differentiation, and migration of NSCs. This is geared toward providing novel application prospects of curcumin in treating psychiatric and neurological disorders by regulating adult neurogenesis.

Topics: Adult; Alzheimer Disease; Cell Differentiation; Curcumin; Humans; Nervous System Diseases; Neurogenesis

Curcumin, an active component of the rhizome turmeric, has gained much attention as a plant-based compound with pleiotropic pharmacological properties. It possesses anti-inflammatory, antioxidant, hypoglycemic, antimicrobial, neuroprotective, and immunomodulatory activities. However, the health-promoting utility of curcumin is constrained due to its hydrophobic nature, water insolubility, poor bioavailability, rapid metabolism, and systemic elimination. Therefore, an innovative stride was taken, and complexes of metals with curcumin have been synthesized. Curcumin usually reacts with metals through the β-diketone moiety to generate metal-curcumin complexes. It is well established that curcumin strongly chelates several metal ions, including boron, cobalt, copper, gallium, gadolinium, gold, lanthanum, manganese, nickel, iron, palladium, platinum, ruthenium, silver, vanadium, and zinc. In this review, the pharmacological, chemopreventive, and therapeutic activities of metal-curcumin complexes are discussed. Metal-curcumin complexes increase the solubility, cellular uptake, and bioavailability and improve the antioxidant, anti-inflammatory, antimicrobial, and antiviral effects of curcumin. Metal-curcumin complexes have also demonstrated efficacy against various chronic diseases, including cancer, arthritis, osteoporosis, and neurological disorders such as Alzheimer's disease. These biological activities of metal-curcumin complexes were associated with the modulation of inflammatory mediators, transcription factors, protein kinases, antiapoptotic proteins, lipid peroxidation, and antioxidant enzymes. In addition, metal-curcumin complexes have shown usefulness in biological imaging and radioimaging. The future use of metal-curcumin complexes may represent a new approach in the prevention and treatment of chronic diseases.

Topics: Alzheimer Disease; Animals; Arthritis; Coordination Complexes; Curcumin; Humans; Nervous System Diseases; Osteoporosis

Curcumin is extensively used in the prevention and treatment of various diseases. Recently, growing attention has been paid to the use of curcumin as a neurogenic and neuroprotective agent. This review study is aimed to collect and categorize the recent findings regarding the effects of curcumin on various neurological diseases through the induction of neural stem cell proliferation and differentiation. In addition, we have discussed the molecular mechanisms modulated by curcumin that contribute to this efficacy and have summarized the recent advancements in the novel delivery strategies used to improve the induction of neural stem cells by curcumin.

Topics: Animals; Curcumin; Humans; Nervous System Diseases; Neural Stem Cells; Neuroprotective Agents

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

Topics: Animals; Antirheumatic Agents; Curcumin; Humans; Nervous System Diseases; Neuroprotective Agents; Rheumatic Diseases; Signal Transduction; Toll-Like Receptor 4

Curcumin's pharmacological properties and its possible benefits for neurological diseases and dementia have been much debated. In vitro experiments show that curcumin modulates several key physiological pathways of importance for neurology. However, in vivo studies have not always matched expectations. Thus, improved formulations of curcumin are emerging as powerful tools in overcoming the bioavailability and stability limitations of curcumin. New studies in animal models and recent double-blinded, placebo-controlled clinical trials using some of these new formulations are finally beginning to show that curcumin could be used for the treatment of cognitive decline. Ultimately, this work could ease the burden caused by a group of diseases that are becoming a global emergency because of the unprecedented growth in the number of people aged 65 and over worldwide. In this review, we discuss curcumin's main mechanisms of action and also data from in vivo experiments on the effects of curcumin on cognitive decline.

Topics: Animals; Clinical Trials as Topic; Cognition; Curcumin; Disease Models, Animal; Drug Compounding; Humans; Nervous System Diseases

Autophagy is the major intracellular machinery for degrading proteins, lipids, polysaccharides, and organelles. This cellular process is essential for the maintenance of the correct cellular balance in both physiological and stress conditions. Because of its role in maintaining cellular homeostasis, dysregulation of autophagy leads to various disease manifestations, such as inflammation, metabolic alterations, aging, and neurodegeneration. A common feature of many neurologic and neuromuscular diseases is the alteration of the autophagy-lysosomal pathways. For this reason, autophagy is considered a target for the prevention and/or cure of these diseases. Dietary intake of polyphenols has been demonstrated to prevent/ameliorate several of these diseases. Thus, natural products that can modulate the autophagy machinery are considered a promising therapeutic strategy. In particular, curcumin, a phenolic compound widely used as a dietary supplement, exerts an important effect in modulating autophagy. Herein, we report on the current knowledge concerning the role of curcumin in modulating the autophagy machinery in various neurological and neuromuscular diseases as well as its role in restoring the autophagy molecular mechanism in several cell types that have different effects on the progression of neurological and neuromuscular disorders.

Topics: Animals; Autophagy; Autophagy-Related Proteins; Curcumin; Dietary Supplements; Humans; Muscle, Skeletal; Nervous System; Nervous System Diseases; Neuromuscular Diseases; Signal Transduction

Neuroinflammatory disease is a general term used to denote the progressive loss of neuronal function or structure. Many neuroinflammatory diseases, including Alzheimer's, Parkinson's, and multiple sclerosis (MS), occur due to neuroinflammation. Neuroinflammation increases nuclear factor-κB (NF-κB) levels, cyclooxygenase-2 enzymes and inducible nitric oxide synthase, resulting in the release of inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). It could also lead to cellular deterioration and symptoms of neuroinflammatory diseases. Recent studies have suggested that curcumin (the active ingredient in turmeric) could alleviate the process of neuroinflammatory disease. Thus, the present mini-review was conducted to summarize studies regarding cellular and molecular targets of curcumin relevant to neuroinflammatory disorders.. A literature search strategy was conducted for all English-language literature. Studies that assessed the various properties of curcuminoids in respect of neuroinflammatory disorders were included in this review.. The studies have suggested that curcuminoids have significant anti- neuroinflammatory, antioxidant and neuroprotective properties that could attenuate the development and symptom of neuroinflammatory disorders. Curcumin can alleviate neurodegeneration and neuroinflammation through multiple mechanisms, by reducing inflammatory mediators (such as TNF-α, IL-1β, nitric oxide and NF-κB gene expression), and affect mitochondrial dynamics and even epigenetic changes.. It is a promising subject of study in the prevention and management of the neuroinflammatory disease. However, controlled, randomized clinical trials are needed to fully evaluate its clinical potential.

Topics: Animals; Curcumin; Humans; Inflammation; Inflammation Mediators; Nervous System Diseases

Curcumin (diferuloylmethane) is a bioactive and major phenolic component of turmeric derived from the rhizomes of curcuma longa linn. For centuries, curcumin has exhibited excellent therapeutic benefits in various diseases. Owing to its anti-oxidant and anti-inflammatory properties, curcumin plays a significant beneficial and pleiotropic regulatory role in various pathological conditions including cancer, cardiovascular disease, Alzheimer's disease, inflammatory disorders, neurological disorders, and so on. Despite such phenomenal advances in medicinal applications, the clinical implication of native curcumin is hindered due to low solubility, physico-chemical instability, poor bioavailability, rapid metabolism, and poor pharmacokinetics. However, these issues can be overcome by utilizing an efficient delivery system. Active scientific research was initiated in 2005 to improve curcumin's pharmacokinetics, systemic bioavailability, and biological activity by encapsulating or by loading curcumin into nanoform(s) (nanoformulations). A significant number of nanoformulations exist that can be translated toward medicinal use upon successful completion of pre-clinical and human clinical trials. Considering this perspective, current review provides an overview of an efficient curcumin nanoformulation for a targeted therapeutic option for various human diseases. In this review article, we discuss the clinical evidence, current status, and future opportunities of curcumin nanoformulation(s) in the field of medicine. In addition, this review presents a concise summary of the actions required to develop curcumin nanoformulations as pharmaceutical or nutraceutical candidates.

Topics: Animals; Anti-Inflammatory Agents; Chemistry, Pharmaceutical; Curcumin; Drug Delivery Systems; Humans; Nanotechnology; Neoplasms; Nervous System Diseases

Exercise and select diets have important influences on health and plasticity of the nervous system, and the molecular mechanisms involved with these actions are starting to be elucidated. New evidence indicates that exercise, in combination with dietary factors, exerts its effects by affecting molecular events related to the management of energy metabolism and synaptic plasticity.. Published studies in animals and humans describing the effects of exercise and diets in brain plasticity and cognitive abilities are discussed.. New evidence indicates that exercise and select diets exert their effects by affecting molecular events related to the management of energy metabolism and synaptic plasticity. An important instigator in the molecular machinery stimulated by exercise is brain-derived neurotrophic factor (BDNF), which acts at the interface of metabolism and plasticity.. Recent studies show that selected dietary factors share similar mechanisms with exercise, and in some cases they can complement the action of exercise. Therefore, exercise and dietary management appear as a non-invasive and effective strategy to counteract neurological and cognitive disorders.

Topics: Animals; Brain Injuries; Brain-Derived Neurotrophic Factor; Cognition Disorders; Curcumin; Diet; Dietary Supplements; Docosahexaenoic Acids; Energy Metabolism; Exercise; Fatty Acids, Omega-3; Food; Humans; Motor Activity; Nervous System Diseases; Neuronal Plasticity

Germacrone (GM) is a terpenoid compound which is reported to have anti-inflammatory and anti-oxidative effects. However, its role in treating traumatic brain injury (TBI) remains largely unknown.. Male C57BL/6 mice were divided into the following groups: control group, TBI group [controlled cortical impact (CCI) model], CCI + 5 mg/kg GM group, CCI + 10 mg/kg GM group and CCI + 20 mg/kg GM group. GM was administered via intraperitoneal injection. The neurological functions (including motor coordination, spatial learning and memory abilities) and brain edema were measured. Nissl staining was used to detect the neuronal apoptosis. Colorimetric assays and enzyme linked immunosorbent assay (ELISA) kits were used to determine the expression levels of oxidative stress markers including myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expressions of inflammatory markers, including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Additionally, protein levels of Nrf2 and p-p65 were detected by Western blot assay.. GM significantly ameliorated motor dysfunction, spatial learning and memory deficits of the mice induced by TBI and it also reduced neuronal apoptosis and microglial activation in a dose-dependent manner. Besides, GM treatment reduced neuroinflammation and oxidative stress compared to those in the CCI group in a dose-dependent manner. Furthermore, GM up-regulated the expression of antioxidant protein Nrf2 and inhibited the expression of inflammatory response protein p-p65.. GM is a promising drug to improve the functional recovery after TBI via repressing neuroinflammation and oxidative stress.

Topics: Animals; Brain; Brain Edema; Brain Injuries, Traumatic; Curcuma; Cytokines; Disease Models, Animal; Drug Evaluation, Preclinical; Male; Memory; Mice, Inbred C57BL; Microglia; Nervous System Diseases; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Phytotherapy; Plant Extracts; Recovery of Function; Sesquiterpenes, Germacrane; Spatial Learning

The development of efficacious and safe drugs for the treatment of neurological diseases related to glutamate toxicity has been a focus in neuropharmacological research. Specifically, discovering antagonists to modulate the activity and kinetics of AMPA receptors, which are the fastest ligand-gated ion channels involved in excitatory neurotransmission in response to glutamate. Thus, the current study investigated novel curcumin derivatives on the biophysical properties of AMPA receptors, specifically on the homomeric GluA2 and the heteromeric GluA2/A3 subunits and assessed for inhibitory actions. The biophysical parameter (i.e., desensitization, deactivation, and peak currents) were measured by using whole-cell patch clamp electrophysiology with and without the administration of the derivatives onto HEK293 cells. CR-NN, CR-NNPh, CR-MeNH, and CR-NO of the tested derivatives showed inhibition on all AMPA receptors up to 6 folds. Moreover, the inhibitory derivatives also increased desensitization and deactivation, which further intensifies the compounds' neuroprotective effects. However, CR-PhCl, CR-PhF, and CR-PhBr did not show any significant changes on the peak current, deactivation or desensitization rates. By comparison to other discovered and widely used antagonist, the prepared curcumin derivatives are not selective to a specific AMPA subunit, instead implement its effect in the same way between all types of AMPA receptors. Additionally, the obtained results provide derivatives that not only noncompetitively inhibit AMPARs but also decrease its biophysical kinetics, specifically desensitization and deactivation rates. Hence, to potentially serve as a new AMPAR inhibitor with therapeutic potential, the current study provides compounds that are non-selective and non-competitive antagonist, which also effect the desensitization and deactivation rates of the receptor.

Topics: Biophysical Phenomena; Curcumin; Electrophysiology; Glutamic Acid; HEK293 Cells; Humans; Nervous System Diseases; Neurons; Patch-Clamp Techniques; Receptors, AMPA

Curcumin is a natural polyphenol that has a broad spectrum of therapeutic characters, including neuroprotective actions against various neurological diseases. However, the molecular mechanism behind its neuroprotective properties remains obscure. The current study investigated the neuroprotective properties of 7 different curcumin derivatives on the gating biophysical properties of AMPA receptors, specifically on the calcium-permeable homomeric GluA1 and calcium impermeable heteromeric GluA1/A2 subunits. Due to the association between excessive activation of AMPARs and neurotoxicity linked to numerous pathologies, we aim to target and manipulate the kinetics of AMPARs through these derivatives. The current study used patch-clamp electrophysiology to measure the whole-cell currents in the presence and absence of the curcumin derivatives onto HEK293 cells expressing AMPA subunits. Our results showed that some of the curcumin derivatives showed an inhibitory effect and altered the gating biophysical properties, namely, deactivation and desensitization. In the presence of those derivatives, the peak current measured was significantly reduced, and the desensitization and deactivation rates decreased as well, achieving slower kinetics of the receptor and depressing its activity. These results suggest that the two most promising derivatives have inhibitory actions and act as allosteric modulators. Many neurological diseases like epilepsy, ALS, and strokes are associated with overactivation of AMPA receptors. We can potentially synthesize a more potent neuroprotective drug to treat those neurological diseases, by understanding the most stable chemical interaction between the derivative and the receptor underlying the reported neuronal depressive properties.

Topics: Calcium; Cell Line; Curcumin; HEK293 Cells; Humans; Kinetics; Nervous System Diseases; Neurons; Neuroprotective Agents; Protein Subunits; Receptors, AMPA

To investigate whether curcumin regulates Notch signaling to cause neuroprotection and neurogenesis after focal ischemia reperfusion injury.. Focal ischemia reperfusion injury was modeled in rats by occluding the middle cerebral artery. These animals were given either curcumin (300 mg/kg) or corn oil (vehicle) by intraperitoneal injection starting 1 h after stroke and continuing for 7 d. In parallel, sham-operated control animals received vehicle. All animals were killed on day 12. The different treatment groups were compared in terms of neurobehavioral deficits, BrdU incorporation, and levels of doublecortin (DCX) and Notch intracellular domain (NICD) using immunohistochemistry, immunofluorescence and Western blotting.. Animals treated with curcumin showed significantly smaller neurobehavioral deficits than vehicle-treated animals after 3, 7, and 12 d of reperfusion (all p < 0.05). Tissue sections from curcumin-treated animals contained significantly greater numbers of BrdU-positive cells (p < 0.05) and BrdU/DCX-positive cells (p < 0.01), as well as significantly higher NICD levels (p < 0.01).. Curcumin may protect from focal cerebral ischemia reperfusion injury as well as stimulate neurogenesis by activating the Notch signaling pathway.

Topics: Analysis of Variance; Animals; Brain; Bromodeoxyuridine; Cell Count; Cerebral Ventricles; Curcumin; Disease Models, Animal; Doublecortin Domain Proteins; Doublecortin Protein; Male; Microtubule-Associated Proteins; Nervous System Diseases; Neurogenesis; Neurologic Examination; Neuropeptides; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Receptors, Notch; Signal Transduction; Stroke; Time Factors

Cisplatin is commonly used against several solid tumors, and oxaliplatin is an effective cytotoxic drug used in colorectal cancer. A major clinical issue affecting 10-40 % of patients treated with cisplatin or oxaliplatin is severe peripheral neuropathy causing sensory, motor, and autonomic dysfunction, with symptoms including cold sensitivity and neuropathic pain. The biochemical basis of the neurotoxicity is uncertain, but is associated with oxidative stress. Curcumin (a natural phenolic yellow pigment) has strong antioxidant, anticancer, and anti-inflammatory actions. Here we report the possible protective effect of curcumin on some cisplatin- and oxaliplatin-induced behavioral, biochemical, and histopathological alterations in rats. Twenty-four hours after the end of treatments some motor and behavioral tests (motor activity, thermal and mechanical nociception, and neuromuscular coordination) were conducted, followed by measuring plasma neurotensin platinum concentration in the sciatic nerve, and studying the histopathology of the sciatic nerve. Oxaliplatin (4 mg/kg) and cisplatin (2 mg/kg) [each given twice weekly, in a total of nine intraperitoneal injections over 4.5 weeks] significantly increased plasma neurotensin concentration, caused specific damage in the histology of the sciatic nerve and produced variable effects in the motor and behavioral tests. Oral curcumin (10 mg/kg, 4 days before the platinum drug, and thereafter, concomitantly with it for 4.5 weeks) reversed the alterations in the plasma neurotensin and sciatic nerve platinum concentrations, and markedly improved sciatic nerve histology in the platinum-treated rats. Larger experiments using a wider dose range of oxaliplatin, cisplatin, and curcumin are required to fully elucidate the possible protective role of curcumin in platinum-induced neurotoxicity.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Behavior, Animal; Cisplatin; Curcumin; Disease Models, Animal; Male; Motor Activity; Nervous System Diseases; Neurotensin; Nociceptive Pain; Organoplatinum Compounds; Oxaliplatin; Peripheral Nervous System; Rats; Rats, Wistar; Sciatic Nerve

Curcumin, a member of the curcuminoid family of compounds, is a yellow colored phenolic pigment obtained from the powdered rhizome of C. longa Linn. Recent studies have demonstrated that curcumin has protective effects against cerebral ischemia/reperfusion injury. However, little is known about its mechanism. Hence, in the present study the neuroprotective potential of curcumin was investigated in middle cerebral artery occlusion (MCAO) induced focal cerebral IR injury. Administration of curcumin 100 and 300 mg/kg i.p. 60 min after MCAO significantly diminished infarct volume, and improved neurological deficit in a dose-dependent manner. Nissl staining showed that the neuronal injury was significantly improved after being treated with curcumin. Curcumin significantly decreased the expression of caspase-3 protein. A higher number of TUNEL-positive cells were found in the vehicle group, but they were significantly decreased in the treated group. Taken together, these results suggest that the neuroprotective potentials of curcumin against focal cerebral ischemic injury are, at least in part, ascribed to its anti-apoptotic effects.

Topics: Analysis of Variance; Animals; Brain Infarction; Caspase 3; Cell Count; Curcumin; Disease Models, Animal; DNA Fragmentation; Dose-Response Relationship, Drug; In Situ Nick-End Labeling; Infarction, Middle Cerebral Artery; Male; Nervous System Diseases; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury