curcumin and Central-Nervous-System-Diseases

Curcumin, isolated from turmeric (Curcuma longa L.) is one of the broadly studied phytomolecule owing to its strong antioxidant and anti-inflammatory potential and has been considered a promising therapeutic candidate in a wide range of disorders. Considering, its low bioavailability, different curcumin analogs have been developed to afford desired pharmacokinetic profile and therapeutic outcome in varied pathological states. Several preclinical and clinical studies have indicated that curcumin ameliorates mitochondrial dysfunction, inflammation, oxidative stress apoptosis-mediated neural cell degeneration and could effectively be utilized in the treatment of different neurodegenerative diseases. Hence, in this review, we have summarized key findings of experimental and clinical studies conducted on curcumin and its analogues with special emphasis on molecular pathways, viz. NF-kB, Nrf2-ARE, glial activation, apoptosis, angiogenesis, SOCS/JAK/STAT, PI3K/Akt, ERK1/2 /MyD88 /p38 MAPK, JNK, iNOS/NO, and MMP pathways involved in imparting ameliorative effects in the therapy of neurodegenerative disorders and associated conditions.

Topics: Antioxidants; Central Nervous System Diseases; Curcuma; Curcumin; Humans; Oxidative Stress; Phosphatidylinositol 3-Kinases

The NLRP3 inflammasome formation and following cytokine secretion is a crucial step in innate immune responses. Internal and external factors may trigger inflammasome activation and result in inflammatory cytokine secretion. Inflammasome formation and activity play critical roles in several disease pathologies such as cardiovascular, metabolic, renal, digestive, and CNS diseases. Underlying pathways are not yet clear, but phytochemicals as alternative therapies have been extensively used for suppression of inflammatory responses.. In this review, we aimed to summarize in vivo and in vitro effects on NLRP3 inflammasome activation of selected phytochemicals.. Three phytochemicals; Sulforaphane, Curcumin, and Resveratrol were selected, and studies were reviewed to clarify their intracellular signaling mechanism in NLRP3 inflammasome activity. PubMed and Scopus databases are used for the search. For sulforaphane, 8 articles, for curcumin, 25 articles, and for resveratrol, 41 articles were included in the review.. In vitro and in vivo studies pointed out that the selected phytochemicals have inhibitory properties on NLRP3 inflammasome activity. However, neither the mechanism is clear, nor the study designs and doses are standardized.

Topics: Animals; Cardiovascular Diseases; Central Nervous System Diseases; Curcumin; Humans; Inflammasomes; Inflammation; Isothiocyanates; NLR Family, Pyrin Domain-Containing 3 Protein; Phytochemicals; Resveratrol; Signal Transduction; Sulfoxides

Topics: Central Nervous System Diseases; Clinical Trials as Topic; Curcumin; Drug Delivery Systems; Humans; Nanoparticles; Neuroprotective Agents

The root extract, curcumin (diferuloylmethane), is a constituent of the ancient herbal medicine Jiawei-Xiaoyaosan that has been used for dyspepsia, stress, and mood disorders. Curcumin engenders a diverse profile of biological actions that result in changes in oxidative stress, inflammation, and cell-death pathways. Combined with its historical use in medical practice and its safety profile, curcumin has been studied for its potential therapeutic applications in cancer, aging, endocrine, immunological, gastrointestinal, and cardiac diseases. In addition, data in animal models and in humans have also begun to be collected in stroke, Alzheimer's disease, and Parkinson's disease. A compelling new body of literature is also mounting to support the efficacy of curcumin in stress and mood disorders. Current understanding of the biological basis for antidepressant-relevant biochemical and behavioral changes shows convergence with some mechanisms known for standard antidepressants. In addition, the mechanisms of the antidepressant-like pharmacology of curcumin also appear to overlap with those of other disease states. Thus, ancient wisdom might be built into this interesting and newly-appreciated natural molecule. Although curcumin is a primary ingredient in anti-aging pills, cosmetic creams, eye treatments, diet products, etc, a key hurdle to the development of curcumin for disease treatment and prevention is overcoming its low oral bioavailability. Although multiple approaches to this problem are being examined, a solution to the bioavailability issue will be needed to ensure appropriate tissue exposures of curcumin in clinical investigation. Progress in this regard is underway.

Topics: Animals; Central Nervous System Diseases; Curcuma; Curcumin; History, Ancient; Humans; Plants, Medicinal

The aim of this study was to compare the protective effects of curcumin, curcumin-β-cyclodextrin nanoparticle curcumin (BCD-CUR) and nanoliposomal curcumin (NLC) on unsymmetrical dimethylhydrazine (UDMH) induced poison in mice. Curcumin, BCD-CUR, and NLC were prepared and their properties of zeta potential, particle size, encapsulation efficiency, and loading capacity were characterized. Eighty-eight male ICR mice on normal chow diet were randomly divided into 11 groups, and intraperitoneally injected with UDMH alone, or together with different doses of curcumin, BCD-CUR or NLC daily for up to 10 d. Enzyme activities of serum alanine transaminase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were analyzed by fully-automatic analyzer and neurotransmitter levels were determined with high performance liquid chromatography (HPLC). 150 mg/kg curcumin treatment alone significantly reduced levels of serum ALT and LDH that were induced by UDMH and markedly increased level of γ-amino butyric acid (GABA) that were reduced by UDMH in the hippocampus. 150 mg/kg BCD-CUR not only decreased significantly the increase of ALT, LDH and glutamate (Glu) but also recovered levels of AST and GABA. 150 mg/kg NLC recovered profoundly levels of AST and GABA while decreased remarkably the UDMH induced increase of ALT, LDH, Glu and 5-hydroxytryptamine (5-HT). In addition, treatments with all tested doses of NLC significantly reduced the UMDH induced dopamine (DA), the monoamine neurotransmitter. NLC had more profound protective effects against liver and central nervous system injury induced by UDMH than a suspension of BCD-CUR or curcumin did in mice.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; beta-Cyclodextrins; Central Nervous System Diseases; Curcumin; Dimethylhydrazines; Dose-Response Relationship, Drug; gamma-Aminobutyric Acid; Hippocampus; L-Lactate Dehydrogenase; Liver; Male; Mice; Mice, Inbred ICR; Nanoparticles; Particle Size; Poisoning

Sevoflurane, a commonly used inhaled anesthetic, can induce neuronal apoptosis in the developing rodent brain and correlate with functional neurological impairment later in life. However, the mechanisms underlying these deleterious effects of sevoflurane remain unclear and no effective treatment is currently available. Herein, the authors investigated whether curcumin can prevent the sevoflurane anesthesia-induced cognitive impairment in mice. Six-day-old C57BL/6 mice were exposed to 3% sevoflurane 2h daily for 3 consecutive days and were treated with curcumin at the dose of 20 mg/kg or vehicle 30 min before the sevoflurane anesthesia from postnatal days 6 (P6) to P8. Cognitive functions were evaluated by open field, Morris water maze, and fear conditioning tests on P61, P63-69, and P77-78, respectively. In another separate experiment, mice were killed on day P8 or P78, and the brain tissues were harvested and then subjected to biochemistry studies. Our results showed that repeated neonatal sevoflurane exposure led to significant cognitive impairment later in life, which was associated with increased neuronal apoptosis, neuroinflammation, oxidative nitrosative stress, and decreased memory related proteins. By contrast, pre-administration of curcumin ameliorated early neuronal apoptosis, neuroinflammation, oxidative nitrosative stress, memory related proteins, and later cognitive dysfunction. In conclusion, our data suggested that curcumin pre-administration can prevent the sevoflurane exposure-induced cognitive impairment later in life, which may be partly attributed to its ability to attenuate the neural apoptosis, inflammation, and oxidative nitrosative stress in mouse brain.

Topics: Age Factors; Anesthetics, Inhalation; Animals; Animals, Newborn; Behavior, Animal; Blood Gas Analysis; Brain; Central Nervous System Diseases; Conditioning, Classical; Curcumin; Drug Administration Schedule; Exploratory Behavior; Fear; Maze Learning; Methyl Ethers; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Random Allocation; Reaction Time; Sevoflurane; Time Factors

We developed a nanoparticles (NPs) library from poly(ethylene glycol)-poly lactic acid comb-like polymers with variable amount of PEG. Curcumin was encapsulated in the NPs with a view to develop a delivery platform to treat diseases involving oxidative stress affecting the CNS. We observed a sharp decrease in size between 15 and 20% w/w of PEG which corresponds to a transition from a large solid particle structure to a "micelle-like" or "polymer nano-aggregate" structure. Drug loading, loading efficacy and release kinetics were determined. The diffusion coefficients of curcumin in NPs were determined using a mathematical modeling. The higher diffusion was observed for solid particles compared to "polymer nano-aggregate" particles. NPs did not present any significant toxicity when tested in vitro on a neuronal cell line. Moreover, the ability of NPs carrying curcumin to prevent oxidative stress was evidenced and linked to polymer architecture and NPs organization. Our study showed the intimate relationship between the polymer architecture and the biophysical properties of the resulting NPs and sheds light on new approaches to design efficient NP-based drug carriers.

Topics: Antioxidants; Biophysical Phenomena; Blood-Brain Barrier; Cell Line, Tumor; Cell Survival; Central Nervous System Diseases; Curcumin; Diffusion; Drug Compounding; Drug Delivery Systems; Drug Liberation; Drug Stability; Humans; Lactates; Models, Chemical; Molecular Conformation; Nanoparticles; Neurons; Neuroprotective Agents; Oxidative Stress; Particle Size; Polyethylene Glycols; Surface Properties

Fluoride is toxic to neuronal development and its excessive intake during pregnancy cause adverse effects on neonatal development. The present study examined the presence of oxidative stress during maternal exposure of fluoride and the therapeutic strategy of Aloe vera, Curcuma longa and Ocimum sanctum extracts in functional prevention of fluoride led oxidative stress. The pregnant Wistar rats were exposed to 100 ppm fluoride in drinking water and pups born to them were supplemented with phytoextracts daily. On 21st postpartum day, the pups were sacrificed to analyse fluoride and oxidative stress markers. Fluoride exposure significantly increased its accumulation, lipid peroxidation and decreased the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase and glutathione levels in discrete regions of the central nervous system (CNS) of pups indicating oxidative stress and inhibited antioxidant defense. The results implied the vulnerability of developing CNS to fluoride toxicity. On phytoextract supplementation, the oxidant devastation was suppressed by regaining antioxidant homeostasis near normal level proving efficacy and therapeutic strategy. Among the phytoextracts supplemented the Ocimum sanctum is found to be more effective.

Topics: Aloe; Animals; Antioxidants; Cariostatic Agents; Catalase; Central Nervous System Diseases; Curcuma; Female; Fluorides; Glutathione; Glutathione Peroxidase; Lipid Peroxidation; Maternal Exposure; Ocimum; Oxidative Stress; Pregnancy; Rats; Rats, Wistar; Superoxide Dismutase

Prion diseases are fatal and at present there are neither cures nor therapies available to delay disease onset or progression in humans. Inspired in part by therapeutic approaches in the fields of Alzheimer's disease and amyotrophic lateral sclerosis, we tested five different drugs, which are known to efficiently pass through the blood-brain barrier, in a murine prion model. Groups of intracerebrally prion-challenged mice were treated with the drugs curcumin, dapsone, ibuprofen, memantine and minocycline. Treatment with antibiotics dapsone and minocycline had no therapeutic benefit. Ibuprofen-treated mice showed severe adverse effects, which prevented assessment of therapeutic efficacy. Mice treated with low- but not high-dose curcumin and mice treated with memantine survived infections significantly longer than untreated controls (P<0.01). These results encourage further research efforts to improve the therapeutic effect of these drugs.

Topics: Animals; Central Nervous System Diseases; Curcumin; Evaluation Studies as Topic; Ibuprofen; Memantine; Mice; Minocycline; Prion Diseases