curcumin has been researched along with Infarction--Middle-Cerebral-Artery* in 27 studies
1 review(s) available for curcumin and Infarction--Middle-Cerebral-Artery
1 trial(s) available for curcumin and Infarction--Middle-Cerebral-Artery
26 other study(ies) available for curcumin and Infarction--Middle-Cerebral-Artery
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High-throughput Sequencing and Bioinformatics Analysis Reveals the Neurogenesis Key Targets of Curcumin Action in Mouse Brain with MCAO.
Experimental studies have shown that curcumin exerts neuroprotective effects in animal models with middle cerebral artery occlusion (MCAO). However, the mechanisms of protective effects of curcumin in MCAO are not fully understood.. This study aims to investigate the key neurogenesis targets of curcumin action in mouse brain with MCAO.. The MCAO models were established in mice. High-throughput sequencing was used to identify differentially expressed mRNA, lncRNA, and circRNA. The reverse expressed mRNAs, lncRNA, and circRNA in sham vs. MCAO and MCAO vs. curcumin were identified. Biological functions were determined by gene ontology (GO) analyses. The protein-protein interaction (PPI) network of neurogenesis-related genes was constructed. Next, neurogenesis-related lncRNA/ circRNA-miRNA-mRNA ceRNA networks were constructed.. The total of reverse expressed 1215 mRNAs, 32 lncRNAs, and 43 circRNAs were filtered based on the 2 series (sham vs. MCAO and MCAO vs. Curcumin). The functional enrichment analysis of 1215 reverse expressed mRNAs found that they were involved in neurogenesis, neuron generation, neurogenesis regulation, and others. The PPI network of neurogenesis-related genes consisted of 115 nodes, including 27 down-regulated genes and 36 up-regulated genes. Furthermore, the neurogenesis-related lncRNA/circRNA-miRNA-mRNA ceRNAs networks were constructed, and 5 lncRNA ceRNA networks and 3 circRNA ceRNA networks were explored.. Our study revealed that curcumin exerts neuroprotective effects by regulating neurogenesis. The neurogenesis-related lncRNA/circRNA-miRNA-mRNA ceRNA networks are potential therapeutic targets of curcumin in MCAO. This study provided a theoretical basis for curcumin exerting neuroprotective effects in MCAO. Topics: Animals; Brain; Computational Biology; Curcumin; Gene Regulatory Networks; High-Throughput Nucleotide Sequencing; Infarction, Middle Cerebral Artery; Mice; MicroRNAs; Neuroprotective Agents; RNA, Circular; RNA, Long Noncoding; RNA, Messenger | 2023 |
Human umbilical cord-derived mesenchymal stem cell transplantation supplemented with curcumin improves the outcomes of ischemic stroke via AKT/GSK-3β/β-TrCP/Nrf2 axis.
Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) engraftment is a promising therapy for acute ischemic stroke (AIS). However, the harsh ischemic microenvironment limits the therapeutic efficacy of hUC-MSC therapy. Curcumin is an anti-inflammatory agent that could improve inflammatory microenvironment. However, whether it enhances the neuroprotective efficacy of hUC-MSC transplantation is still unknown. In the present study, we investigated the therapeutic efficacy and the possible mechanism of combined curcumin and hUC-MSC treatment in AIS.. Middle cerebral artery occlusion (MCAO) mice and oxygen glucose deprivation (OGD) microglia were administrated hUC-MSCs with or without curcumin. Neurological deficits assessment, brain water content and TTC were used to assess the therapeutic effects of combined treatment. To elucidate the mechanism, MCAO mice and OGD microglia were treated with AKT inhibitor MK2206, GSK3β activator sodium nitroprusside (SNP), GSK3β inhibitor TDZD-8 and Nrf2 gene knockout were used. Immunofluorescence, flow cytometric analysis, WB and RT-PCR were used to evaluate the microglia polarization and the expression of typical oxidative mediators, inflammatory cytokines and the AKT/GSK-3β/β-TrCP/Nrf2 pathway protein.. Compared with the solo hUC-MSC-grafted or curcumin groups, combined curcumin-hUC-MSC therapy significantly improved the functional performance outcomes, diminished the infarct volumes and the cerebral edema. The combined treatment promoted anti-inflammatory microglia polarization via Nrf2 pathway and decreased the expression of ROS, oxidative mediators and pro-inflammatory cytokines, while elevating the expression of the anti-inflammatory cytokines. Nrf2 knockout abolished the antioxidant stress and anti-inflammation effects mediated with combined treatment. Moreover, the combined treatment enhanced the phosphorylation of AKT and GSK3β, inhibited the β-TrCP nucleus translocation, accompanied with Nrf2 activation in the nucleus. AKT inhibitor MK2206 activated GSK3β and β-TrCP and suppressed Nrf2 phosphorylation in nucleus, whereas MK2206 with the GSK3β inhibitor TDZD-8 reversed these phenomena. Furthermore, combined treatment followed by GSK3β inhibition with TDZD-8 restricted β-TrCP nucleus accumulation, which facilitated Nrf2 expression.. We have demonstrated that combined curcumin-hUC-MSC therapy exerts anti-inflammation and antioxidant stress efficacy mediated by anti-inflammatory microglia polarization via AKT/GSK-3β/β-TrCP/Nrf2 axis and an improved neurological function after AIS. Topics: Animals; Anti-Inflammatory Agents; Antioxidants; beta-Transducin Repeat-Containing Proteins; Curcumin; Cytokines; Glycogen Synthase Kinase 3 beta; Humans; Infarction, Middle Cerebral Artery; Ischemic Stroke; Mesenchymal Stem Cell Transplantation; Mice; NF-E2-Related Factor 2; Proto-Oncogene Proteins c-akt; Umbilical Cord | 2023 |
Curcumin nanoemulsion ameliorates brain injury in diabetic rats.
Diabetes mellitus has been implicated in the exacerbation of cerebral ischemic injuries. Among the most promising therapeutic approaches is the combination of nutraceuticals and nanotechnology. Curcumin has been termed "the magic molecule", and it was proven to exert several therapeutic actions. Therefore, the aim of the presented work was to investigate the therapeutic effects of curcumin nanoemulsion (NC) administered orally on the middle cerebral artery occlusion and reperfusion (MCAO/Re)-induced cerebral damage in rats with streptozotocin-induced diabetes. The cerebral injury was induced in rats by MCAO/Re 6 weeks after single intraperitoneal STZ injection (50 mg/kg; i.p.). MCAO/Re diabetic rats were then treated with NC (50 and 100 mg/kg; bw; p.o.) for two consecutive weeks. The results of the present study showed that oral treatment of MCAO/Re diabetic rats with NC was associated with a marked attenuation of the neurological deficit score as well as the brain imbalance of the redox homeostasis. NC treatment was also associated with decline in the brain expression of tumor necrosis factor, interleukin-1β, COX-2, cleaved caspase-3, and nuclear factor kappa B. In addition, the expression of glucose transporter 1 proteins upon treatment was restored. PRACTICAL APPLICATIONS: From all these results, it can be concluded that oral supplementation of curcumin nanoemulsion (NC) in diabetic rats reduced the brain injury via augmentation of the expression of glucose transporter 1, as well as its antioxidant and anti-inflammatory properties. Therefore, NC could be delineated as a promising treatment option for cerebral ischemia in diabetic patients. Topics: Animals; Brain Injuries; Curcumin; Diabetes Mellitus, Experimental; Glucose Transporter Type 1; Infarction, Middle Cerebral Artery; Rats; Reperfusion Injury | 2022 |
Design, green synthesis, antioxidant activity screening, and evaluation of protective effect on cerebral ischemia reperfusion injury of novel monoenone monocarbonyl curcumin analogs.
Topics: Animals; Antioxidants; Cells, Cultured; Curcumin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Design; Drug Evaluation, Preclinical; Green Chemistry Technology; Infarction, Middle Cerebral Artery; Male; Mice; Mice, Inbred C57BL; Molecular Structure; Oxidative Stress; PC12 Cells; Protective Agents; Rats; Reperfusion Injury; Structure-Activity Relationship | 2021 |
Hexahydrocurcumin alleviated blood-brain barrier dysfunction in cerebral ischemia/reperfusion rats.
Hexahydrocurcumin (HHC), a major metabolite of curcumin, has been reported to have protective effects against ischemic and reperfusion damage. The goal of the present research was to examine whether HHC could alleviate brain damage and ameliorate functional outcomes by diminishing the blood-brain barrier (BBB) damage that follows cerebral ischemia/reperfusion.. Middle cerebral artery occlusion was induced for 2 h in rats followed by reperfusion. The rats were divided into three groups: sham-operated, vehicle-treated, and HHC-treated groups. At the onset of reperfusion, the rats were immediately intraperitoneally injected with 40 mg/kg HHC. At 48 h after reperfusion, the rats were evaluated for neurological deficits and TTC staining. At 24 h and 48 h after reperfusion, animals were sacrificed, and their brains were extracted.. Treatment with HHC reduced neurological scores, infarct volume, morphological changes, Evans blue leakage and immunoglobulin G extravasation. Moreover, HHC treatment reduced BBB damage and neutrophil infiltration, downregulated myeloperoxidase, ICAM-1, and VCAM-1, upregulated tight junction proteins (TJPs), and reduced aquaporin 4 expression and brain water content.. These results revealed that HHC treatment preserved the BBB from cerebral ischemia/reperfusion injury by regulating TJPs, attenuating neutrophil infiltration, and reducing brain edema formation. Topics: Animals; Aquaporin 4; Blood-Brain Barrier; Brain; Brain Edema; Brain Ischemia; Curcumin; Infarction; Infarction, Middle Cerebral Artery; Male; Rats; Rats, Wistar; Reperfusion Injury; Zonula Occludens-1 Protein | 2020 |
Curcumin Prevents Brain Damage and Cognitive Dysfunction During Ischemic-reperfusion Through the Regulation of miR-7-5p.
This study was to investigate the potential protective effects of curcumin in cerebral ischemia-reperfusion (CIR) and its regulation of miR-7.. Rats were occluded by middle cerebral artery occlusion (MCAO) for 1.5 h and reperfused for 2 h to establish a local CIR model. After 24 hours of model establishment, MCAO rats were given curcumin for 3 days by intragastric administration. PC12 cells were cultured for 6 h in oxygen-glucose deprivation medium and then reoxygenated for 24 h to establish an oxygenglucose deprivation/reoxygenation (OGD/R) model. The OGD/R model cells were treated with curcumin for 48 h.. Curcumin inhibited the decrease of miR-7-5p expression and an increase of RelA p65 expression induced by CIR and ODG/R. RelA p65 was a target of miR-7-5p. MiR-7-5p antagonists were able to counteract the effect of curcumin on the expression of RelA p65 in ischemic brain tissue of MCAO rats and OGD/R model cells. Curcumin improved OGD/R-induced inhibition of cell activity, necrosis and apoptosis. Curcumin significantly reduced the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, reactive oxygen species (ROS) and malondialdehyde (MDA) and increased the activity of superoxide dismutases (SOD) and catalase (CAT) in OGD/R-induced cells. Curcumin may inhibit OGD/R-induced cell damage by regulating miR-7-5p. Curcumin improved cerebral infarction, nerve damage and cognitive dysfunction in rats with CIR, which may be related to the regulation of miR-7-5p/RelA p65 axis.. Curcumin exerts cerebral protection by attenuating cell necrosis and apoptosis, inflammatory response and oxidative stress following CIR, which may be related to its regulation of the miR-7/RELA p65 axis. Topics: Animals; Apoptosis; Cognition Disorders; Curcumin; Gene Expression Regulation; Infarction, Middle Cerebral Artery; Male; MicroRNAs; Neuroprotective Agents; Oxidative Stress; Rats; Reactive Oxygen Species; Reperfusion Injury | 2019 |
Tetrahydrocurcumin epigenetically mitigates mitochondrial dysfunction in brain vasculature during ischemic stroke.
Topics: Animals; Blood-Brain Barrier; Brain; Brain Ischemia; Curcumin; Infarction, Middle Cerebral Artery; Male; Mice, Inbred C57BL; Mitochondria; Reperfusion Injury; Stroke | 2019 |
CNB-001, a pleiotropic drug is efficacious in embolized agyrencephalic New Zealand white rabbits and ischemic gyrencephalic cynomolgus monkeys.
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 | 2019 |
Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy.
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 | 2018 |
Neuroprotective Effect of Curcumin Against Cerebral Ischemia-Reperfusion Via Mediating Autophagy and Inflammation.
Curcumin, a polyphenolic compound extracted from Curcuma longa, has drawn attention for its effective bioactivities against ischemia-induced injury. This study aimed to evaluate the neuroprotective effect of curcumin and investigate the underlying mechanism that mediates autophagy and inflammation in an animal model of middle cerebral artery occlusion (MCAO) in rats. Curcumin was delivered to Sprague Dawley male rats at a dose of 200 mg/kg curcumin by intraperitoneal injection 30 min after ischemia-reperfusion (I/R). LY294002, a specific inhibitor of the PI3K/Akt/mTOR pathway, as well as anisomycin, an activator of TLR4/p38/MAPK, was administered by ventricle injection 30 min before MCAO. The same volume of saline was given as a control. Brain infarction and neurological function were determined 24 h post-MCAO. Immunoblotting and immunofluorescence were used to detect alterations in autophagy-relevant proteins Akt, p-Akt, mTOR, p-mTOR, LC3-II, and LC3-I, and inflammation-related proteins TLR4, p-38, p-p38, and IL-1 in the ipsilateral hemisphere. Cerebral I/R injury resulted in significant alterations of LC3-II/LC3-I, IL-1, TLR4, and p-p38. Curcumin in MCAO rats significantly improved brain damage and neurological function by upregulating p-Akt and p-mTOR and downregulating LC3-II/LC3-I, IL-1, TLR4, p-38, and p-p38. However, these protective effects against ischemia could be suppressed when LY294002 or anisomycin was included. Curcumin exerts neuroprotective effects by attenuating autophagic activities through mediating the PI3K/Akt/mTOR pathway, while also suppressing an inflammatory reaction by regulating the TLR4/p38/MAPK pathway. Furthermore, this study indicates that curcumin could be an effective therapy for patients afflicted with ischemia. Topics: Animals; Anti-Inflammatory Agents; Autophagy; Autophagy-Related Proteins; Brain; Curcumin; Infarction, Middle Cerebral Artery; Interleukin-1; Male; MAP Kinase Signaling System; Neuroprotective Agents; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Toll-Like Receptor 4; TOR Serine-Threonine Kinases | 2018 |
Curcumin improves diabetes mellitus‑associated cerebral infarction by increasing the expression of GLUT1 and GLUT3.
Curcumin is characterized by anti‑inflammatory, anti‑oxidative, antiviral, antifibrotic, anticoagulation and glucose regulatory functions. However, whether it is protective in diabetes mellitus‑associated cerebral infarction remains to be fully elucidated. In the present study, it was demonstrated for the first time, to the best of our knowledge, that curcumin markedly improved neurological deficits, cerebral infarct volume and brain edema rate following middle cerebral artery occlusion (MCAO) surgery. It was also shown that the expression levels of glucose transporter (GLUT)1 and GLUT3 were reduced in the MCAO group. However, following curcumin treatment, the levels of GLUT1 and GLUT3 were markedly increased. In addition, curcumin markedly decreased cell apoptosis, indicating an anti‑apoptotic role of curcumin in the brain. To further evaluate whether curcumin prevented cell apoptosis by modulating the expression of GLUT1 and GLUT3, small interfering RNAs targeting GLUT1 and GLUT3 were selected. It was found that the knockdown of GLUT1 and GLUT3 inhibited the abundance of GLUT1, GLUT3 and B‑cell lymphoma 2, even following incubation with curcumin. These data showed that curcumin protected brain cells from apoptosis and cerebral infarction, predominantly by upregulating GLUT1 and GLUT3. Topics: Animals; Apoptosis; Brain; Curcumin; Diabetes Complications; Glucose Transporter Type 1; Glucose Transporter Type 3; Infarction, Middle Cerebral Artery; Male; Neuroprotective Agents; Rats, Sprague-Dawley; Up-Regulation | 2018 |
Potential therapeutic and protective effect of curcumin against stroke in the male albino stroke-induced model rats.
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 | 2017 |
Curcumin pretreatment attenuates inflammation and mitochondrial dysfunction in experimental stroke: The possible role of Sirt1 signaling.
The effects of curcumin (CCM) on cerebral ischemia/reperfusion injury are not well understood. The aim of this study was to investigate whether CCM attenuates inflammation and mitochondrial dysfunction in a rat model of cerebral ischemia/reperfusion injury and whether Sirt1 is involved in these potential protective effects. Sirtinol, a Sirt1 inhibitor, was used to elucidate the underlying mechanism. Rats were subjected to 2h of transient middle cerebral artery occlusion (MCAO), followed by reperfusion for 24h. Brain magnetic resonance imaging (MRI) was used to detect infarct volumes. Neurological scores and brain water content were also assessed. Levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in the brain were detected using commercial enzyme-linked immunosorbent assay (ELISA) kits. Expression of SIRT1, acetylated p53 (Ac-p53), Bcl-2, and Bax was measured by western blotting. Our results suggested that CCM exerted a neuroprotective effect, as shown by reduced infarct volumes and brain edema and improved neurological scores. CCM also exerted anti-inflammatory effects, as indicated by decreased TNF-α and IL-6 levels in the brain. CCM elevated mitochondrial membrane potential, mitochondrial complex I activity, and mitochondrial cytochrome c levels, but reduced cytosolic cytochrome c levels. Moreover, CCM upregulated SIRT1 and Bcl-2 expression and downregulated Ac-p53 and Bax expression. These effects of CCM were abolished by sirtinol. In conclusion, our results demonstrate that CCM treatment attenuates ischemic stroke-induced brain injury via activation of SIRT1. Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Brain Edema; Curcumin; Disease Models, Animal; Drug Administration Schedule; Gene Expression Regulation; Histocompatibility Antigens Class I; Infarction, Middle Cerebral Artery; Inflammation; Male; Membrane Potential, Mitochondrial; Mitochondrial Diseases; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury; Signal Transduction; Sirtuin 1 | 2016 |
Curcumin by down-regulating NF-kB and elevating Nrf2, reduces brain edema and neurological dysfunction after cerebral I/R.
Oxidation, inflammation, and apoptosis are three critical factors for the pathogenic mechanism of cerebral ischemia/reperfusion (I/R) injury. Curcumin exhibits substantial biological properties via anti-oxidation, anti-inflammation and anti-apoptotic effects; however, the molecular mechanism underlying the effects of curcumin against cerebral I/R injury remains unclear.. To investigate the effects of curcumin on cerebral I/R injury associated with water content, infarction volume, and the expression of nuclear factor-kappa-B (NF-κB) and nuclear factor-erythroid-related factor-2 (Nrf2).. Middle cerebral artery occlusion (MCAO, 1-hour occlusion and 24-hour reperfusion) was performed in male Wistar rats (n=64) as a cerebral I/R injury model. In the MCAO+CUR group, the rats were administered curcumin (300mg/kg BW, i.p.) at 30min after occlusion. The same surgical procedures were performed in SHAM rats without MCAO occlusion. At 24h post-operation, the parameters, including neurological deficit scores, blood brain barrier (BBB) disruption, water content, and infarction volume, were determined. Brain tissue NF-κB and Nrf2 expression levels were assayed through immunohistochemistry.. Compared with the SHAM group, BBB disruption, neurological deficit, and increased brain water content and infarction volume were markedly demonstrated in the MCAO group. NF-κB expression was enhanced in the MCAO group. However, in the MCAO+CUR group, the upregulation of Nrf2, an anti-oxidation related protein, was consistent with a significant decline in the water content, infarction volume, and NF-κB expression.. The protective effects of curcumin against cerebral I/R injury reflect anti-oxidation, anti-inflammation and anti-apoptotic activities, resulting in the elevation of Nrf2 and down-regulation of NF-κB. Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Blood-Brain Barrier; Brain Edema; Capillary Permeability; Curcumin; Disease Models, Animal; Down-Regulation; Infarction, Middle Cerebral Artery; Male; Motor Activity; Neuroprotective Agents; NF-E2-Related Factor 2; Oxidative Stress; Rats, Wistar; Reperfusion Injury; Signal Transduction; Time Factors; Transcription Factor RelA; Up-Regulation | 2016 |
Identification of proteins regulated by curcumin in cerebral ischemia.
Curcumin is known to have a neuroprotective effect against cerebral ischemia. The objective of this study was to identify various proteins that are differentially expressed by curcumin treatment in focal cerebral ischemia using a proteomic approach.. Adult male rats were treated with vehicle or curcumin 1 h after middle cerebral artery occlusion. Brain tissues were collected 24 h after the onset of middle cerebral artery occlusion, and cerebral cortices proteins were identified by two-dimensional gel electrophoresis and mass spectrometry.. We detected several proteins with altered expression levels between vehicle- and curcumin-treated animals. Among these proteins, ubiquitin carboxy-terminal hydrolase L1, isocitrate dehydrogenase, adenosylhomocysteinase, and eukaryotic initiation factor 4A were decreased in the vehicle-treated animal, and curcumin treatment attenuated the injury-induced decreases of these proteins. Conversely, pyridoxal phosphate phosphatase was increased in the vehicle-treated animal, and curcumin treatment prevented decreases in this protein. The identified altered proteins are associated with cellular metabolism and differentiation.. The results of this study suggest that curcumin exerts a neuroprotective effect by regulating the expression of various proteins in focal cerebral ischemia. Topics: Animals; Brain; Curcumin; Electrophoresis, Gel, Two-Dimensional; Gene Expression Regulation; Infarction, Middle Cerebral Artery; Male; Mass Spectrometry; Neuroprotective Agents; Phytotherapy; Plant Extracts; Random Allocation; Rats, Sprague-Dawley | 2016 |
Curcumin attenuates glutamate neurotoxicity in the hippocampus by suppression of ER stress-associated TXNIP/NLRP3 inflammasome activation in a manner dependent on AMPK.
Curcumin is a natural polyphenolic compound in Curcuma longa with beneficial effects on neuronal protection. This study aims to investigate the action of curcumin in the hippocampus subjected to glutamate neurotoxicity. Glutamate stimulation induced reactive oxygen species (ROS), endoplasmic reticulum stress (ER stress) and TXNIP/NLRP3 inflammasome activation, leading to damage in the hippocampus. Curcumin treatment in the hippocampus or SH-SY5Y cells inhibited IRE1α and PERK phosphorylation with suppression of intracellular ROS production. Curcumin increased AMPK activity and knockdown of AMPKα with specific siRNA abrogated its inhibitory effects on IRE1α and PERK phosphorylation, indicating that AMPK activity was essential for the suppression of ER stress. As a result, curcumin reduced TXNIP expression and inhibited NLRP3 inflammasome activation by downregulation of NLRP3 and cleaved caspase-1 induction, and thus reduced IL-1β secretion. Specific fluorescent probe and flow cytometry analysis showed that curcumin prevented mitochondrial malfunction and protected cell survival from glutamate neurotoxicity. Moreover, oral administration of curcumin reduced brain infarct volume and attenuated neuronal damage in rats subjected to middle cerebral artery occlusion. Immunohistochemistry showed that curcumin inhibited p-IRE1α, p-PERK and NLRP3 expression in hippocampus CA1 region. Together, these results showed that curcumin attenuated glutamate neurotoxicity by inhibiting ER stress-associated TXNIP/NLRP3 inflammasome activation via the regulation of AMPK, and thereby protected the hippocampus from ischemic insult. Topics: AMP-Activated Protein Kinases; Animals; Behavior, Animal; Carrier Proteins; Cell Line, Tumor; Curcumin; Endoplasmic Reticulum Stress; Glutamic Acid; Hippocampus; Humans; Infarction, Middle Cerebral Artery; Inflammasomes; Interleukin-1beta; Interleukin-6; Male; Membrane Potential, Mitochondrial; Mice, Inbred ICR; Motor Activity; Neuroprotective Agents; NLR Family, Pyrin Domain-Containing 3 Protein; Rats, Sprague-Dawley; Reactive Oxygen Species; Taurochenodeoxycholic Acid; Thioredoxins | 2015 |
Targets of vascular protection in acute ischemic stroke differ in type 2 diabetes.
Hemorrhagic transformation is an important complication of acute ischemic stroke, particularly in diabetic patients receiving thrombolytic treatment with tissue plasminogen activator, the only approved drug for the treatment of acute ischemic stroke. The objective of the present study was to determine the effects of acute manipulation of potential targets for vascular protection [i.e., NF-κB, peroxynitrite, and matrix metalloproteinases (MMPs)] on vascular injury and functional outcome in a diabetic model of cerebral ischemia. Ischemia was induced by middle cerebral artery occlusion in control and type 2 diabetic Goto-Kakizaki rats. Treatment groups received a single dose of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), the nonspecific NF-κB inhibitor curcumin, or the broad-spectrum MMP inhibitor minocycline at reperfusion. Poststroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated. All acute treatments reduced MMP-9 and hemorrhagic transformation in diabetic groups. In addition, acute curcumin and minocycline therapy reduced edema in these animals. Improved neurological function was observed in varying degrees with treatment, as indicated by beam-walk performance, modified Bederson scores, and grip strength; however, infarct size was similar to untreated diabetic animals. In control animals, all treatments reduced MMP-9 activity, yet bleeding was not improved. Neuroprotection was only conferred by curcumin and minocycline. Uncovering the underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies. Topics: Animals; Curcumin; Diabetes Mellitus, Type 2; Edema; Hemorrhage; Infarction, Middle Cerebral Artery; Locomotion; Male; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Metalloporphyrins; Minocycline; Neuroprotective Agents; NF-kappa B; Peroxynitrous Acid; Rats; Rats, Mutant Strains; Rats, Wistar | 2013 |
Effect of combined treatment with curcumin and candesartan on ischemic brain damage in mice.
The combined effects of curcumin and candesartan were investigated in brain ischemia induced by middle cerebral artery (MCA) occlusion (MCAO). Male mice were classified into 5 groups. The mice were killed 24 hours after MCAO, and each group was divided into 2 halves. In one half, brain homogenate was collected for antioxidant enzyme activity determination, and in the other half, samples were obtained for red color intensity determination in brain slices. The untreated group exhibited significantly reduced cerebral blood flow, increased lipid peroxide levels and heart rate, decreased superoxide dismutase (SOD) and glutathione-S-transferase (GST) activity, and reduced red color intensity compared with the sham group. Combination treatment with curcumin and candesartan significantly restored SOD and GST activity, thiobarbituric acid reactive substances, heart rate, blood flow, and red color intensity compared with the untreated group. The use of each drug alone significantly restored SOD and blood flow compared with the sham and untreated groups, heart rate decreased with curcumin alone, and red color intensity and nitric oxide level increased with candesartan alone. These results indicate that curcumin synergistically enhances the inhibitory action of candesartan on brain ischemia through suppression of blood flow changes and oxidative stress via antioxidant properties, suggesting beneficial combined effects of curcumin and candesartan on ischemic brain damage. Topics: Animals; Antioxidants; Benzimidazoles; Biphenyl Compounds; Blood Flow Velocity; Brain; Cerebrovascular Circulation; Curcumin; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Glutathione Transferase; Heart Rate; Infarction, Middle Cerebral Artery; Lipid Peroxidation; Male; Mice; Neuroprotective Agents; Regional Blood Flow; Superoxide Dismutase; Tetrazoles; Time Factors | 2011 |
Curcumin improves outcomes and attenuates focal cerebral ischemic injury via antiapoptotic mechanisms in rats.
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. In the present study, we tested the effects of curcumin in focal cerebral ischemia in rats and the possible mechanisms. Adult male Sprague-Dawley rats were treated with curcumin (100, 300 and 500 mg/kg) administered intraperitoneally after 60 min of occlusion (beginning of reperfusion). Neurological score and infarct volume were assessed at 24 and 72 h. Oxidative stress was evaluated by malondialdehyde assay and the apoptotic mechanisms were studied by Western blotting. Curcumin treatment significantly reduced infarct volume and improved neurological scores at different time points compared with the vehicle-treated group. Curcumin treatment decreased malondialdehyde levels, cytochrome c, and cleaved caspase 3 expression and increased mitochondrial Bcl-2 expression. Inhibition of oxidative stress with curcumin treatment improves outcomes after focal cerebral ischemia. This neuroprotective effect is likely exerted by antiapoptotic mechanisms. Topics: Animals; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Behavior, Animal; Blotting, Western; Cell Death; Curcumin; Dose-Response Relationship, Drug; Fluorescent Antibody Technique; Infarction, Middle Cerebral Artery; Injections, Intraperitoneal; Ischemic Attack, Transient; Male; Middle Cerebral Artery; Neurons; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Sprague-Dawley; Time Factors; Treatment Outcome | 2010 |
Curcumin upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia.
Oxidative and cytotoxic damage plays an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Curcumin is proved to elicit a vanity of biological effects through its antioxidant and anti-inflammatory properties. But the mechanisms underlying are poorly understood. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) coordinates expression of genes required for free radical scavenging, detoxification of xenobiotics, and maintenance of redox potential. This study evaluated the time course expression regularity of Nrf2, HO-1 and the curcumin's role in cerebral ischemia and its potential mechanism.. Male, Sprague-Dawley rats were subjected to permanent focal cerebral ischemia by right MCA occlusion. Experiment 1 was used to evaluate the expression of Nrf2 and HO-1 in the cerebral ischemia, 6 time points was included. Experiment 2 was used to detect curcumin's neuroprotection in cerebral ischemia. At 24 h neurological deficit was evaluated using a modified six point scale; brain water content was measured; infarct size was analysed with 2, 3, 5-triphenyltetrazolium chloride (TTC). Immunohistochemistry, RT-PCR, Western blot, and confocal microscope were used to analyse the expression of Nrf2 and HO-1.. Compared with sham-operated, Nrf2 and HO-1 were upregulated at gene and protein level in ischemic brain, beginning at 3 h and peaking at 24 h after MCAO (P<0.05). Curcumin high dose (100 mg/kg) upregulated Nrf2 and HO-1 in MCAO-affected brain tissue and reduced infarct volume (P<0.05), brain water content (P<0.05) and behavioral deficits (P<0.05) caused by MCAO.. Nrf2 and HO-1 were induced at the early stage after MCAO. Curcumin protected the brain from damage caused by MCAO, this effect may be through upregulation of the transcription factor Nrf2 expression. Nrf2 may be one of the strategic targets for cerebral ischemic therapies. Topics: Animals; Brain; Brain Edema; Brain Infarction; Brain Ischemia; Curcumin; Cytoprotection; Disease Models, Animal; Enzyme Inhibitors; Gene Expression Regulation; Heme Oxygenase-1; Infarction, Middle Cerebral Artery; Male; Neuroprotective Agents; NF-E2-Related Factor 2; Rats; Rats, Sprague-Dawley; RNA, Messenger; Time Factors; Up-Regulation | 2009 |
Dose dependence and therapeutic window for the neuroprotective effects of curcumin in thromboembolic model of rat.
Curcumin (diferuloylmethane), an active ingredient of turmeric, obtained from the powdered rhizomes of Curcuma longa Linn., has been traditionally recognized for treatment of several diseases. To evaluate the potential clinical use of curcumin, we determined the dose dependence of its effects in the therapeutic window and of the neuroprotective efficacy in a cerebral thromboembolic model of the rat. Rats were subjected to occlusion of the middle cerebral artery (MCAo) by a thrombus and treated with different doses of curcumin or the vehicle at 4h after ischemia. The animals were assessed after 24h for motor performance and neurological deficit. The rats were sacrificed immediately afterwards for evaluation of infarct, edema volume, estimation of nitrate and nitrite levels, neutrophil infiltration and levels of GSH and glutathione peroxidase (GSH-Px) in brain tissue. Curcumin reduced in a dose-dependent manner the ischemia-induced cerebral infarct and edema volume and attenuated neurological deficits observed after 24h. Curcumin reduced post-ischemic brain neutrophil infiltration, nitrate and nitrite levels and ameliorated the loss of GSH-Px and tends to increase the GSH levels but not significantly in the brain tissue. Neuronal levels of reactive oxygen species, peroxynitrite, and nitric oxide were lowered and in brain cryosections inducible nitric oxide synthase expression were significantly inhibited after treatment with curcumin. The present study is the first evidence of effectiveness of curcumin when given 4h post-ischemia in the rat thromboembolic stroke models, as it reduces infarct volume, ameliorates the sensory motor function and significantly attenuated the nitrosative stress. Topics: Animals; Behavior, Animal; Brain Edema; Brain Ischemia; Cerebrovascular Circulation; Curcumin; Disease Models, Animal; Dose-Response Relationship, Drug; Glutathione Peroxidase; Immunohistochemistry; Infarction, Middle Cerebral Artery; Male; Motor Activity; Neuroprotective Agents; Nitrates; Nitric Oxide; Nitrites; Peroxidase; Peroxynitrous Acid; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Treatment Outcome | 2008 |
Neuroprotective effect of curcumin on transient focal cerebral ischemia in rats.
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 | 2008 |
Anti-ischemic effect of curcumin in rat brain.
Turmeric has been in use since ancient times as a condiment and due to its medicinal properties. Curcumin, the yellow colouring principle in turmeric, is polyphenolic and major active constituent. Besides anti-inflammatory, thrombolytic and anticarcinogenic activities, curcumin also possesses strong antioxidant property. In view of the novel combination of properties, neuroprotective efficacy of curcumin was studied in rat middle cerebral artery occlusion (MCAO) model. Rats were subjected to 2 h of focal ischemia followed by 72 h of reperfusion. They were pre-treated with curcumin (100 mg/kg, po) for 5 days prior to MCAO and for another 3 days after MCAO. The parameters studied were behavioural, biochemical and histological. Treatment with curcumin could significantly improve neurobehavioral performance compared to untreated ischemic rats as judged by its effect on rota-rod performance and grid walking. A significant inhibition in lipid peroxidation and an increase in superoxide dismutase (SOD) activity in corpus striatum and cerebral cortex was observed following treatment with curcumin in MCAO rats as compared to MCAO group. Intracellular calcium levels were decreased following treatment with curcumin in MCAO rats. Histologically, a reduction in the infarct area from 33% to 24% was observed in MCAO rats treated with curcumin. The study demonstrates the protective efficacy of curcumin in rat MCAO model. Topics: Animals; Behavior, Animal; Brain; Brain Ischemia; Calcium; Curcumin; Enzyme Inhibitors; Humans; Infarction, Middle Cerebral Artery; Lipid Peroxidation; Male; Neuroprotective Agents; Rats; Rats, Wistar; Superoxide Dismutase | 2008 |
Neuroprotective efficacy and therapeutic window of curcuma oil: in rat embolic stroke model.
Among the naturally occurring compounds, turmeric from the dried rhizome of the plant Curcuma longa has long been used extensively as a condiment and a household remedy all over Southeast Asia. Turmeric contains essential oil, yellow pigments (curcuminoids), starch and oleoresin. The present study was designed for investigating the neuroprotective efficacy and the time window for effective therapeutic use of Curcuma oil (C. oil).. In the present study, the effect of post ischemic treatment of C.oil after ischemia induced by occlusion of the middle cerebral artery in the rat was observed. C.oil (500 mg/kg body wt) was given 4 hrs post ischemia. The significant effect on lesion size as visualized by using diffusion-weighted magnetic resonance imaging and neuroscore was still evident when treatment was started 4 hours after insult. Animals were assessed for behavioral deficit scores after 5 and 24 hours of ischemia. Subsequently, the rats were sacrificed for evaluation of infarct and edema volumes and other parameters.. C.oil ameliorated the ischemia induced neurological functional deficits and the infarct and edema volumes measured after 5 and 24 hrs of ischemia. After 24 hrs, immunohistochemical and Western blot analysis demonstrated that the expression of iNOS, cytochrome c and Bax/Bcl-2 were altered after the insult, and antagonized by treatment with C.oil. C.oil significantly reduced nitrosative stress, tended to correct the decreased mitochondrial membrane potential, and also affected caspase-3 activation finally apoptosis.. Here we demonstrated that iNOS-derived NO produced during ischemic injury was crucial for the up-regulation of ischemic injury targets. C.oil down-regulates these targets this coincided with an increased survival rate of neurons. Topics: Animals; Apoptosis; Behavior, Animal; Blotting, Western; Caspase 3; Curcuma; Enzyme Activation; Infarction, Middle Cerebral Artery; Intracranial Embolism; Neurons; Neuroprotective Agents; Nitric Oxide; Plant Oils; Rats; Rats, Sprague-Dawley | 2008 |
Curcuma oil: reduces early accumulation of oxidative product and is anti-apoptogenic in transient focal ischemia in rat brain.
Turmeric is a source of numerous aromatic compounds isolated from powdered rhizomes of Curcuma longa Linn. The constituents are present as volatile oil, the Curcuma oil (C.oil), semi-solid oleoresins and non-volatile compounds such as curcumin. A rapidly expanding body of data provides evidence of the anti-cancer action of Curcumin, and most importantly in the present context, its neuroprotective activity. Almost nothing is known about such activity of C.oil. We report that C.oil (500 mg Kg(-1) i.p.) 15 min before 2 h middle cerebral artery occlusion (MCAo) followed by 24 h reflow in rats significantly diminished infarct volume, improved neurological deficit and counteracted oxidative stress. The percent ischemic lesion volume on diffusion-weighted imaging was significantly attenuated. Mitochondrial membrane potential, reactive oxygen species, peroxynitrite levels, caspase-3 activities leading to delayed neuronal death were significantly inhibited after treatment with C.oil. These results suggest that the neuroprotective activity of C.oil against cerebral ischemia is associated with its antioxidant activities and further; there is attenuation of delayed neuronal death via a caspase-dependent pathway. C.oil appears to be a promising agent not only for the treatment of cerebral stroke, but also for the treatment of other disorders associated with oxidative stress. Topics: Animals; Antioxidants; Apoptosis; Behavior, Animal; Caspase 3; Catalase; Curcuma; Glutathione Peroxidase; Infarction, Middle Cerebral Artery; Ischemic Attack, Transient; Male; Malondialdehyde; Medicine, Ayurvedic; Motor Activity; Neurons; Neuropsychological Tests; Oxidation-Reduction; Oxidative Stress; Plant Oils; Rats; Rats, Sprague-Dawley; Superoxide Dismutase | 2008 |
Neuroprotective effect of curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in rats.
Free radical induced neuronal damage is implicated in cerebral ischemia reperfusion (IR) injury and antioxidants are reported to have neuroprotective activity. Several in vitro and in vivo studies have proved the antioxidant potential of curcumin and its metabolites. Hence, in the present study the neuroprotective potential of curcumin was investigated in middle cerebral artery occlusion (MCAO) induced focal cerebral IR injury. 2 h of MCAO and 22 h of reperfusion resulted in the infarct volume of 210.39 +/- 31.25 mm3. Administration of curcumin 100 and 300 mg/kg, i.p. 30 min. after MCAO produced 37.23 +/- 5.10% and 46.39 +/- 10.23% (p < 0.05) reduction in infarct volume, respectively. Ischemia induced cerebral edema was reduced in a dose dependent manner. Curcumin at 300 mg/kg, i.p. produced 50.96 +/- 6.04% reduction in edema (p < 0.05) volume. Increase in lipid peroxidation after MCAO in ipsilateral and contralateral hemisphere of brain was observed, which was reduced by curcumin (300 mg/kg, i.p.)-treatment. Decrease in superoxide dismutase and glutathione peroxidase activity was observed in ipsilateral hemisphere of MCAO animal. Curcumin-treatment (300 mg/kg, i.p.) prevented IR injury mediated fall in glutathione peroxide activity. Peroxynitrite measured using rhodamine123 fluorescence and anti-nitrotyrosine immunofluorescence indicated increased peroxynitrite formation after IR insult. Curcumin-treatment reduced peroxynitrite formation and hence the extent of tyrosine nitration in the cytosolic proteins. These results suggest the neuroprotective potential of curcumin in cerebral ischemia and is mediated through its antioxidant activity. Topics: Animals; Behavior, Animal; Body Temperature; Brain; Brain Edema; Brain Ischemia; Cerebrovascular Circulation; Curcumin; Fluorescent Antibody Technique; Glutathione Peroxidase; Infarction, Middle Cerebral Artery; Lipid Peroxidation; Male; Neuroprotective Agents; Peroxynitrous Acid; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Tyrosine | 2004 |