curcumin and Stroke

Stroke is the second leading cause of morbidity and mortality globally. Treatments for stroke are limited, and preventive treatments are scarce. Curcumin (CUR) has several biological effects, as described in the literature, which highlight its antioxidant and neuroprotective effects. Therefore, this qualitative systematic review aimed to investigate the effects of CUR on damage caused by stroke in rodent models. A systematic search was performed on three databases PubMed, Scopus, and Web of Science. In addition, the risk-of-bias and quality of the studies were assessed using SYRCLE and Collaborative Approach for Meta-Analysis and Review of Animal Data from Experimental Studies, respectively. The selection, inclusion, and exclusion criteria were established by the authors. At the end of our systematic search of the three databases, we found a total of 728 articles. After excluding duplicates and triplicates and reading the abstracts, keywords, and full texts, 53 articles were finally included in this systematic review. CUR exerts several beneficial effects against the damage caused by both ischemic and hemorrhagic stroke, via different pathways. However, because of its low bioavailability, Free-form CUR only exerted significant effects when it was administered at high concentrations. In contrast, when CUR was administered using nanostructured systems, positive responses were observed even at low concentrations. The mechanisms of action of CUR, free or in nanostructure, are extremely important for the recovery of injured brain tissue after a stroke; CUR has neuroprotective, antioxidant, anti-inflammatory, and anti-apoptotic effects and helps to maintain the integrity of the blood-brain barrier. Finally, we concluded that CUR presents an extremely important and significant response profile against the damage caused by stroke, making it a possible therapeutic candidate for individuals affected by this disease.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Curcumin; Neuroprotective Agents; Stroke

Despite being a major global health concern, cerebral ischemia/stroke has limited therapeutic options. Tissue plasminogen activator (tPA) is the only available medication to manage acute ischemic stroke, but this medication is associated with adverse effects and has a narrow therapeutic time window. Curcumin, a polyphenol that is abundantly present in the rhizome of the turmeric plant (

Topics: Animals; Brain Ischemia; Curcumin; Neuroprotective Agents; Stroke; Tissue Plasminogen Activator

Curcumin is widely consumed in Asia either as turmeric directly or as one of the culinary ingredients in food recipes. The benefits of curcumin in different organ systems have been reported extensively in several neurological diseases and cancer. Curcumin has got its global recognition because of its strong antioxidant, anti-inflammatory, anti-cancer, and antimicrobial activities. Additionally, it is used in diabetes and arthritis as well as in hepatic, renal, and cardiovascular diseases. Recently, there is growing attention on usage of curcumin to prevent or delay the onset of neurodegenerative diseases. This review summarizes available data from several recent studies on curcumin in various neurological diseases such as Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Huntington's disease, Prions disease, stroke, Down's syndrome, autism, Amyotrophic lateral sclerosis, anxiety, depression, and aging. Recent advancements toward increasing the therapeutic efficacy of curcuma/curcumin formulation and the novel delivery strategies employed to overcome its minimal bioavailability and toxicity studies have also been discussed. This review also summarizes the ongoing clinical trials on curcumin for different neurodegenerative diseases and patent details of curcuma/curcumin in India.

Topics: Alzheimer Disease; Amyotrophic Lateral Sclerosis; Animals; Anxiety; Autistic Disorder; Biological Availability; Curcuma; Curcumin; Dementia; Depression; Drug Delivery Systems; Glioma; Humans; Huntington Disease; Multiple Sclerosis; Muscular Atrophy, Spinal; Neuroprotective Agents; Parkinson Disease; Patents as Topic; Prion Diseases; Stroke

The epigenetic impact of curcumin in stroke and neurodegenerative disorders is curiosity-arousing. It is derived from Curcuma longa (spice), possesses anti-oxidative, anti-inflammatory, anti-lipidemic, neuro-protective and recently shown to exhibit epigenetic modulatory properties. Epigenetic studies include DNA methylation, histone modifications and RNA-based mechanisms which regulate gene expression without altering nucleotide sequences. Curcumin has been shown to affect cancer by altering epigenetic changes but its role as an epigenetic agent in cerebral stroke has not been much explored. Although curcumin possesses remarkable medicinal properties, the bioavailability of curcumin has limited its success in epigenetic studies and clinical trials. The present review is therefore designed to look into epigenetic mechanisms that could be induced with curcumin during stroke, along with its molecular designing with different moieties that may increase its bioavailability. Curcumin has been shown to be encapsulated in exosomes, nano-vesicles (<200 nm), thereby showing its therapeutic effects in brain diseases. Curcumin delivered through nanoparticles has been shown to be neuroregenerative but the use of nanoparticles in brain has limitations. Hence, curcumin-encapsulated exosomes along with curcumin-primed exosomes (exosomes released by curcumin-treated cells) are much needed to be explored to broadly look into their use as a novel therapy for stroke.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Epigenesis, Genetic; Exosomes; Humans; Neuroprotective Agents; Stroke

Curcumin has been investigated in preclinical and translational stroke models because of its pleiotropic 'neuroprotective' activities. Since curcumin has poor blood-brain barrier (BBB) penetration following acute administration, creative medicinal chemistry has been used to modify the parent curcumin molecule, resulting in second generation curcuminoids, which have enhanced BBB penetration, improved pharmacokinetics and interact with multiple viable targets to treat stroke.. This review covers epidemiological, preclinical and translational data published between 2002 and 2010.. There are two main goals: First, epidemiological data comparing the incidence of stroke in North America to that of India, a country where curcumin is a main-stay of the diet is presented. Second, the pharmacological characteristics of curcuminoids are detailed to determine if they should be further studied in translational stroke models for safety and efficacy prior to initiating clinical trials.. Curcumin and curcuminoids are neuroprotective in a variety of preclinical stroke models. The novel multi-target curcuminoid, CNB-001, has a superior safety and pharmacokinetic profile and should be further developed as an acute monotherapy or to be used in conjunction with thrombolytics for acute ischemic stroke.

Topics: Animals; Blood-Brain Barrier; Brain Ischemia; Curcumin; Drug Delivery Systems; Humans; India; Neuroprotective Agents; North America; Permeability; Pyrazoles; Stroke

Topics: Anti-Inflammatory Agents; Anticoagulants; Clinical Trials as Topic; Curcumin; Humans; Hypolipidemic Agents; Neuroprotective Agents; Stroke

Oxidative stress and inflammation are two key pathophysiological mechanisms that lead to neuronal apoptosis and brain damage following ischemia/reperfusion (I/R) injury. Because of their complex pathological mechanisms and the presence of the blood-brain barrier, the treatment of I/R is severely limited. Inspired by the fact that Macrophage membranes (MM) can cross the blood-brain barrier, we have developed a new multifunctional bionic particle (MSAOR@Cur). The modification of Sialic acid (SA) on the surface of Angelica polysaccharides (APS), the attachment of Resveratrol (Res) using the ROS-responsive bond oxalate bond as a linker arm, constitutes amphiphilic nanoparticles with an inner core encapsulated with curcumin (SAOR@Cur), and finally the use of MM camouflage to integrate the neuroprotection of APS, the free radical scavenging of Res, and the anti-inflammation of curcumin (Cur) in one strategy. Interestingly, the experimental results show that MSAOR@Cur can successfully deliver curcumin to the area of ischemia-reperfusion injury.

Topics: Curcumin; Humans; N-Acetylneuraminic Acid; Nanoparticles; Oxidative Stress; Polysaccharides; Reperfusion Injury; Resveratrol; Stroke

Curcumin (Cur) is widely used as an anti-inflammation agent and has anti-depression potential. Neuroinflammation mediated by Ca

Topics: Animals; Calcium; Calcium Signaling; Curcumin; Depression; Male; Microglia; Purinergic P2X Receptor Agonists; Purinergic P2X Receptor Antagonists; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P2X7; Stroke

Topics: Animals; Blood-Brain Barrier; Brain; Brain Ischemia; Curcumin; Infarction, Middle Cerebral Artery; Male; Mice, Inbred C57BL; Mitochondria; Reperfusion Injury; Stroke

Ischemic stroke is an acute neurodegenerative disease that is extremely devastating to patients, their families and society. Stroke is inadequately treated even with endovascular procedures and reperfusion therapy. Using an extensive translational screening process, we have developed a pleiotropic cytoprotective agent with the potential to positively impact a large population of brain ischemia patients and revolutionize the process used for the development of new drugs to treat complex brain disorders. In this unique translational study article, we document that the novel curcumin-based compound, CNB-001, when administered as a single intravenous dose, has significant efficacy to attenuate clinically relevant behavioral deficits following ischemic events in agyrencephalic rabbits when administered 1 h post-embolization and reduces infarct growth in gyrencephalic non-human primates, when administered 5 min after initiation of middle cerebral artery occlusion. CNB-001 is safe and does not increase morbidity or mortality in either research species. Mechanistically, CNB-001 inhibits human 5- and 15-lipoxygenase in vitro, and can attenuate ischemia-induced inflammatory markers, and oxidative stress markers, while potentially promoting synaptic plasticity mediated by enhanced brain-derived neurotrophic factor (BDNF).

Topics: Administration, Intravenous; Animals; Behavior, Animal; Brain Ischemia; Curcumin; Disease Progression; Infarction, Middle Cerebral Artery; Lipoxygenase Inhibitors; Macaca fascicularis; Magnetic Resonance Imaging; Male; Neuroprotective Agents; Pyrazoles; Rabbits; Stroke

The safe and effective delivery of drugs is a major obstacle in the treatment of ischemic stroke. Exosomes hold great promise as an endogenous drug delivery nanosystem for the treatment of cerebral ischemia given their unique properties, including low immunogenicity, innate stability, high delivery efficiency, and ability to cross the blood-brain barrier (BBB). However, exosome insufficient targeting capability limits their clinical applications. In this study, the c(RGDyK) peptide has been conjugated to the exosome surface by an easy, rapid, and bio-orthogonal chemistry. In the transient middle cerebral artery occlusion (MCAO) mice model, The engineered c(RGDyK)-conjugated exosomes (cRGD-Exo) target the lesion region of the ischemic brain after intravenous administration. Furthermore, curcumin has been loaded onto the cRGD-Exo, and administration of these exosomes has resulted in a strong suppression of the inflammatory response and cellular apoptosis in the lesion region. The results suggest a targeting delivery vehicle for ischemic brain based on exosomes and provide a strategy for the rapid and large-scale production of functionalized exosomes.

Topics: Animals; Cell Line, Tumor; Curcumin; Disease Models, Animal; Exosomes; HeLa Cells; Humans; Infarction, Middle Cerebral Artery; Injections, Intravenous; Male; Mice; Mice, Inbred C57BL; Peptides; Pharmaceutical Vehicles; Stroke

Curcumin, a natural antioxidant isolated from Curcuma longa, has been reported to exert neuroprotective effect in animal models of ischemic stroke. However, the underlying mechanism is still not fully understood. The purpose of this study was to investigate the effect of curcumin treatment on neuronal apoptosis in the periinfarct cortex after cerebral ischemia/reperfusion (I/R) injury and in mouse N2a cells after oxygen-glucose deprivation/reoxygenation (OGD/R) injury and its underlying mechanism.. The cerebral I/R injury was established by 1-hr middle cerebral artery occlusion (MCAO) and reperfusion in mice. Infarct volume was determined by TTC staining, and neurological score was evaluated by mNSS. Cell morphology in the ischemic boundary zone were detected by HE staining. The number and apoptotic rate of neurons in ischemic boundary zone were assayed by immunohistochemistry and TUNEL, respectively. Mouse neuroblastoma N2a cells were subjected to OGD/R. Cell viability was assessed with CCK-8. The mitochondrial membrane potential was measured using JC-1 staining. The expression of Bax, Bcl-2, and caspase-3 was detected using Western blotting. Besides, cellular distribution of Bax was determined by immunofluorescence assays.. Curcumin promotes neuron survival

Topics: Animals; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Brain Ischemia; Caspase 3; Cell Line, Tumor; Cell Survival; Cells, Cultured; Curcumin; Disease Models, Animal; Mice; Neurons; Neuroprotective Agents; Proto-Oncogene Proteins c-bcl-2; Reperfusion Injury; Stroke

Antioxidants have shown great promise in stroke prevention. Diarylheptanoids (also known as diphenylheptanoids) are a small class of plant secondary metabolites that possess antioxidant activity greater than that of α-tocopherol. Curcumin is the best known member and is mainly extracted from turmeric. This study aimed to explore whether curcumin has a preventive effect on stroke.. Stroke-prone spontaneously hypertensive rats (SHRsp) were randomly divided into control group (n = 10) and curcumin group (n = 10), and saline or curcumin (100 mg/kg/day) was administrated daily. Vascular endothelial function was examined by the relaxation of the artery in response to acetylcholine (ACH). The levels of reactive oxygen species (ROS) and nitric oxide (NO) were measured by using dihydroethidium (DHE) and 4, 5-diaminofluorescein (DAF-2 DA), respectively. The expression of uncoupling protein 2 (UCP2) was examined by RT-PCR and immunoblotting.. Administration of curcumin significantly delayed the onset of stroke and increased the survival of SHRsp, which was ascribed to decreased ROS and improved endothelial dependent relaxation of carotid arteries. In the presence of UCP2 inhibitor genipin, both curcumin-mediated decrease of ROS and increase of NO production were blocked.. Our study suggests that curcumin exerts a stroke preventive effect by attenuating oxidative stress to improve vascular endothelial function, which might be associated with UCP2 signaling.

Topics: Animals; Antioxidants; Carotid Arteries; Cells, Cultured; Curcumin; Disease Models, Animal; Endothelium, Vascular; Human Umbilical Vein Endothelial Cells; Humans; Hypertension; Male; Nitric Oxide; Oxidative Stress; Rats, Inbred SHR; Reactive Oxygen Species; Signal Transduction; Stroke; Uncoupling Protein 2; Vasodilation

The role of Peroxiredoxin 6 (Prdx6) in brain ischemia remains unclear. Curcumin (Cur) treatment elicits neuroprotective effects against cerebral ischemic injury, and the associated mechanisms may involve Prdx6. In this study, we investigated whether Prdx6 and the transcription factor specific protein 1 (SP1) were involved in the antioxidant effect of Cur after stoke.. Focal cerebral ischemic injury was induced by transient middle cerebral artery occlusion for 2 hours in male Sprague-Dawley rats treated with or without Prdx6 siRNA. Expression of Prdx6 in the penumbra was assessed by Real-Time PCR (RT-PCR), Western blot analysis, and immunoflourescent staining. In addition, infarct volume, neurological deficit score, and oxidative stress were evaluated. Prdx6 levels were also determined in the presence and absence of SP1 antagonist mithramycin A (MTM-A).. Cur treatment upregulated Prdx6 protein expression and the number of Prdx6-positive neuronal cells 24 hours after reperfusion. Cur treatment also attenuated oxidative stress and induced neuroprotective effects against ischemic damage, whereas the beneficial effects of Cur treatment were lost in animals treated with Prdx6-siRNA. Prdx6 upregulation by Cur treatment was abolished by SP1 antagonists MTM.. Prdx6 upregulation by Cur treatment attenuates ischemic oxidative damage through SP1 induction in rats after stroke. This represents a novel mechanism of Cur-induced neuroprotection against cerebral ischemia.

Topics: Animals; Brain; Brain Ischemia; Curcumin; Gene Expression Regulation, Enzymologic; Male; Neuroprotective Agents; Oxidation-Reduction; Peroxiredoxin VI; Rats; Rats, Sprague-Dawley; Sp1 Transcription Factor; Stroke; Up-Regulation

The present study was carried out to understand the therapeutic effect of curcumin (CUR) against stroke in the experimental animal model. The study investigates the healing effect of CUR on mitochondrial dysfunction and inflammation.. Male albino, Wistar strain rats were used for the induction of middle cerebral artery occlusion (MCAO), and reperfusion. Enzyme-linked immunosorbent assay (ELISA) was used for the determination of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the brain region. Western blot analysis was used to determine the protein expression levels of Bax, Bcl-2, p53, and Sirt1.. The water level was determined in brain region by using standard method. Experimental results indicated that the use of CUR significantly reduced brain edema and water content. IL-6 and TNF-α were significantly reduced in the brain region following use of CUR. Mitochondrial membrane potential (MMP) also reduced significantly after CUR treatment. Protein expression of p53 and Bax were significantly reduced, whereas Bcl-2 and Sirt1 were increased following CUR treatment.. Taking all these data together, it is suggested that the use of CUR may be a potential therapeutic agent for the treatment of stroke.

Topics: Animals; Brain Edema; Curcumin; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; Infarction, Middle Cerebral Artery; Inflammation; Interleukin-6; Male; Membrane Potential, Mitochondrial; Mitochondria; Rats; Rats, Wistar; Stroke; Tumor Necrosis Factor-alpha

The pathogenesis of visual dysfunction in stroke remains unclear. The objective of this study was to explore retinal damage in stroke spontaneously hypertensive rats (SHR) and evaluate the role of curcumin in the retinal injury after stroke. Mature male SHR were used as the animal model for hypertension and age-matched male Wistar-Kyoto (WKY) rats as the normotensive controls. The rat model of stroke was made by bilateral vertebral artery electrocoagulation combined with transient bilateral common carotid artery ligation. The animals were randomly divided into sham group, ischemia/reperfusion group, solvent control group, and curcumin treatment group. Each group was subdivided into 2 h, 6 h, 24 h, 72 h, and 7 day after reperfusion. Blood pressure was measured in SHR and WKY rats. Eye fundus was examined in living animals, and then, tissue specimens were collected for histologic examination, terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling, and immunohistochemistry. Retinopathy, induced by I/R, was more serious in rats with hypertension than that in normotensive rats (retinal thickness index, p = 0.004). The number of apoptosis in retinal capillary cells and neurons reduced significantly in the curcumin-treated groups. Curcumin treatment inhibited phosphorylated c-Jun N-terminal kinase (JNK) expression in SHR after retinal I/R injury. Thus, hypertension aggravated retinal I/R injury after stroke. Curcumin, a specific inhibitor of JNK, can prevent the development of hypertensive retinopathy after I/R injury by inhibiting apoptosis in retinal capillary cells and neurons.

Topics: Animals; Apoptosis; Blood Pressure; Brain Ischemia; Capillaries; Curcumin; Disease Models, Animal; Enzyme Inhibitors; Hypertension; Hypertensive Retinopathy; JNK Mitogen-Activated Protein Kinases; Male; Neurons; Protective Agents; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reperfusion Injury; Retina; Stroke

The purpose of the present experiment was to investigate whether hexahydrocurcumin (HHC) attenuates brain damage and improves functional outcome via the activation of antioxidative activities, anti-inflammation, and anti-apoptosis following cerebral ischemia/reperfusion (I/R). In this study, rats with cerebral I/R injury were induced by a transient middle cerebral artery occlusion (MCAO) for 2 h, followed by reperfusion. The male Wistar rats were randomly divided into five groups, including the sham-operated, vehicle-treated, 10 mg/kg HHC-treated, 20 mg/kg HHC-treated, and 40 mg/kg HHC-treated I/R groups. The animals were immediately injected with HHC by an intraperitoneal administration at the onset of cerebral reperfusion. After 24 h of reperfusion, the rats were tested for neurological deficits, and the pathology of the brain was studied by 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, and terminal deoxynucleotidyltransferase UTP nick end labeling (TUNEL) staining. In addition, the brain tissues were prepared for protein extraction for Western blot analysis, a malondialdehyde (MDA) assay, a nitric oxide (NO) assay, a superoxide dismutase (SOD) assay, a glutathione (GSH) assay, and a glutathione peroxidase (GSH-Px) assay. The data revealed that the neurological deficit scores and the infarct volume were significantly reduced in the HHC-treated rats at all doses compared to the vehicle group. Treatment with HHC significantly attenuated oxidative stress and inflammation, with a decreased level of MDA and NO and a decreased expression of NF-κB (p65) and cyclooxygenase-2 (COX-2) in the I/R rats. HHC also evidently increased Nrf2 (nucleus) protein expression, heme oxygenase-1 (HO-1) protein expression, the antioxidative enzymes, and the superoxide dismutase (SOD) activity. Moreover, the HHC treatment also significantly decreased apoptosis, with a decrease in Bax and cleaved caspase-3 and an increase in Bcl-XL, which was in accordance with a decrease in the apoptotic neuronal cells. Therefore, the HHC treatment protects the brain from cerebral I/R injury by diminishing oxidative stress, inflammation, and apoptosis. The antioxidant properties of HHC may play an important role in improving functional outcomes and may offer significant neuroprotection against I/R damage.

Topics: Animals; Antioxidants; Curcumin; Disease Models, Animal; Inflammation; Rats; Reperfusion Injury; Stroke

To investigate the neuroprotective effect of chronic curcumin supplementation on the rat forebrain prior to ischemia and reperfusion.. Forebrain ischemia was induced by bilateral common carotid artery occlusion for 1/2 hour, followed by reperfusion for 72 hours. Older rats were divided into five groups: Group I received 300 mg/kg oral curcumin for 21 days before ischemia and 300 mg/kg intraperitoneal curcumin after ischemia; Group II received 300 mg/kg intraperitoneal curcumin after ischemia; Group III received 300 mg/kg oral curcumin for 21 days before ischemia; Group IV had only ischemia; Group V was the sham-operated group. The forebrain was rapidly dissected for biochemical parameter assessment and histopathological examination.. In forebrain tissue, enzyme activities of superoxide dismutase, glutathione peroxidase, and catalase were significantly higher in Group I than Groups II or III (p < 0.05) while xanthine dehydrogenase and malondialdehyde enzyme activities and concentrations of interleukin-6 and TNF-alpha were significantly lower in Group I when compared to Groups II and III (p < 0.05). A significant reduction in neurological score was observed after 24 and 72 hours in the curcumin-treated groups compared with the ischemic group. We also found a marked reduction in apoptotic index after 72 hours in the groups receiving curcumin. Significantly more TUNEL-positive cells were observed in the ischemic group compared to those treated with curcumin.. We demonstrated the neuroprotective effect of chronic curcumin supplement on biochemical parameters, neurological scores and apoptosis following ischemia and reperfusion injury in rats.

Topics: Animals; Apoptosis; Catalase; Curcumin; Glutathione Peroxidase; Interleukin-6; Ischemia; Male; Malondialdehyde; Neuroprotective Agents; Prosencephalon; Rats; Reperfusion Injury; Stroke; Superoxide Dismutase; Tumor Necrosis Factor-alpha; Xanthine Dehydrogenase

Stroke is a one of the leading causes of disease and deaths worldwide, which causes irreversible deterioration of the central nervous system. Curcuminoids are reported to have a potential role in the amelioration of cerebral ischemia but they exhibit low serum and tissue levels due to low solubility and poor absorption. Curcumin (CUR), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC)-loaded PNIPAM nanoparticles (NPs) were prepared by free radical polymerization and characterized for particles size, entrapment efficiency, zeta potential, in vitro release and ex vivo permeation study. Optimized CUR, DMC and BDMC-loaded NPs had the mean size of 92.46 ± 2.8, 91.23 ± 4.2 and 94.28 ± 1.91 nm; zeta potential of -16.2 ± 1.42, -15.6 ± 1.33 and -16.6 ± 1.21 mV; loading capacity of 39.31 ± 3.7, 38.91 ± 3.6 and 40.61 ± 3.6% and entrapment efficiency of 84.63 ± 4.2, 84.71 ± 3.99 and 85.73 ± 4.31%, respectively. Ultra-performance liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectroscopy based bioanalytical method was developed and validated for pharmacokinetics, biodistribution, brain-targeting efficiency and brain drug-targeting potential studies post-intranasal (i.n.) administration which showed enhanced bioavailability of curcuminoids in brain as compared to intravenous administration. Improved neurobehavioural activity (locomotor and grip strength) and reduced cytokines levels (TNF-α and IL-1β) was observed in middle cerebral artery occlusion induced cerebral ischemic rats after i.n. administration of curcuminoids NPs. Finally, the toxicity study was performed which revealed safe nature of developed NPs.

Topics: Acrylic Resins; Administration, Intranasal; Animals; Biological Availability; Brain; Brain Ischemia; Chromatography, High Pressure Liquid; Curcumin; Diarylheptanoids; Drug Delivery Systems; Nanoparticles; Nasal Mucosa; Particle Size; Rats; Rats, Wistar; Spectrometry, Mass, Electrospray Ionization; Stroke; Tandem Mass Spectrometry; Tissue Distribution

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

We sought to test the hypothesis that turmeric-derived curcuminoids limit reperfusion brain injury in an experimental model of stroke via blockade of early microvascular inflammation during reperfusion.. Male Sprague Dawley rats subjected to MCAO/R were treated with turmeric-derived curcuminoids (vs. vehicle) 1 hour prior to reperfusion (300 mg/kg ip). Neutrophil adhesion to the cerebral microcirculation and measures of neutrophil and endothelial activation were assayed during early reperfusion (0-4 hours); cerebral infarct size, edema, and neurological function were assessed at 24 hours. Curcuminoid effects on TNFα-stimulated human brain microvascular endothelial cell (HBMVEC) were assessed.. Early during reperfusion following MCAO, curcuminoid treatment decreased neutrophil rolling and adhesion to the cerebrovascular endothelium by 76% and 67% and prevented >50% of the fall in shear rate. The increased number and activation state (CD11b and ROS) of neutrophils were unchanged by curcuminoid treatment, while increased cerebral expression of TNFα and ICAM-1, a marker of endothelial activation, were blocked by >30%. Curcuminoids inhibited NF-κB activation and subsequent ICAM-1 gene expression in HBMVEC.. Turmeric-derived curcuminoids limit reperfusion injury in stroke by preventing neutrophil adhesion to the cerebrovascular microcirculation and improving shear rate by targeting the endothelium.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; CD11b Antigen; Cells, Cultured; Curcumin; Endothelial Cells; Endothelium, Vascular; Humans; Leukocyte Rolling; Male; Neutrophil Activation; Neutrophils; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury; Stroke

Oxidative stress and inflammatory damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The development of new strategies for enhancing drug delivery to the brain is of great importance in diagnostics and therapeutics of central nervous diseases. The present study examined the hypothesis that intranasal delivery of nanoformulation of curcuminoids would reduce oxidative stress-associated brain injury after middle cerebral artery occlusion (MCAO). The rats were subjected to 2 h of MCAO followed by 22 h reperfusion, after which the grip strength, locomotor activity was performed. The effects of treatment in the rats were assessed by grip strength, locomotor activity and biochemical studies (glutathione peroxidase, glutathione reductase, lipid peroxidation, superoxide dismutase, and catalase) in the brain. Pretreatment with polymeric N-isopropyl acryl amide (PNIPAM) nanoparticles formulation of all three curcuminoids (curcumin (Cur), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC)) at doses (100 μg/kg body weight) given intranasally was effective in bringing significant changes on all the parameters. While nanoformulation of curcumin at a dose of 100 μg/kg body weight was most active in the treatment of cerebral ischemia as compared to others nanoformulation of curcuminoids. The potency of antioxidant activity significantly decreased in the order of PNIPAM nanoformulation of Cur > DMC >> BDMC, thus suggesting the critical role of methoxy groups on the phenyl ring.

Topics: Acrylic Resins; Animals; Antioxidants; Biomarkers; Curcumin; Diarylheptanoids; Hand Strength; Light; Motor Activity; Nanoparticles; Oxidative Stress; Particle Size; Rats; Rats, Wistar; Scattering, Radiation; Stroke; Thiobarbituric Acid Reactive Substances

Acute ischemic stroke is a major risk for morbidity and mortality in our aging population. Currently only one drug, the thrombolytic tissue plasminogen activator, is approved by the US Food and Drug Administration to treat stroke. Therefore, there is a need to develop new drugs that promote neuronal survival following stroke. We have synthesized a novel neuroprotective molecule called CNB-001 (a pyrazole derivative of curcumin) that has neurotrophic activity, enhances memory, and blocks cell death in multiple toxicity assays related to ischemic stroke. In this study, we tested the efficacy of CNB-001 in a rigorous rabbit ischemic stroke model and determined the molecular basis of its in vivo activity. CNB-001 has substantial beneficial properties in an in vitro ischemia assay and improves the behavioral outcome of rabbit ischemic stroke even when administered 1 h after the insult, a therapeutic window in this model comparable to tissue plasminogen activator. In addition, we elucidated the protein kinase pathways involved in neuroprotection. CNB-001 maintains the calcium-calmodulin-dependent kinase signaling pathways associated with neurotrophic growth factors that are critical for the maintenance of neuronal function. On the basis of its in vivo efficacy and novel mode of action, we conclude that CNB-001 has a great potential for the treatment of ischemic stroke as well as other CNS pathologies.

Topics: Animals; Brain Ischemia; Cells, Cultured; Curcumin; Disease Models, Animal; Male; Mice; Mice, Inbred BALB C; Motor Activity; Neuroprotective Agents; Pyrazoles; Rabbits; Stroke; Time Factors; Treatment Outcome