Generic placeholder image

Current Neurovascular Research

Editor-in-Chief

ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

Research Article

Curcumin Alleviates Cerebral Ischemia-reperfusion Injury by Inhibiting NLRP1-dependent Neuronal Pyroptosis

Author(s): Lifa Huang*, Xu Li, Yajun Liu, Xiaolong Liang, Hui Ye, Chao Yang, Lin Hua and Xin Zhang*

Volume 18, Issue 2, 2021

Published on: 07 June, 2021

Page: [189 - 196] Pages: 8

DOI: 10.2174/1567202618666210607150140

Price: $65

Abstract

Background: Cerebral ischemia-reperfusion injury is caused by a blood reperfusion injury in the ischemic brain and usually occurs in the treatment stage of ischemic disease, which can aggravate brain tissue injury.

Objective: Curcumin was reported to exert a good therapeutic effect on neural cells against ischemia- reperfusion injury, However, the mechanism is not clear.

Methods: In this study, Oxygen-Glucose Deprivation (OGD) model of fetal rat cerebral cortical neurons and the Middle Cerebral Artery Occlusion (MCAO) model of rats were employed to mimic cerebral ischemia-reperfusion injury in vitro and in vivo, respectively.

Results: We confirmed that curcumin has a promotive effect on neuronal proliferation and an inhibitory effect on neuronal pyroptosis. Furthermore, we found that curcumin could improve cerebral infarction. The results of western blotting showed that curcumin down-regulated the expression of nucleotide-binding oligomerization domain-containing protein-, leucine-rich repeats-, and pyrin domain-containing protein 1 (NLRP1), cysteinyl aspartate-specific protease 1 (caspase-1), gasdermin D (GSDMD), IL-1β, IL-6, TNF-α, and iNOS proteins in OGD and MCAO models. NLRP1- dependent neuronal pyroptosis played an important role in cerebral ischemia-reperfusion injury.

Conclusion: Curcumin could effectively inhibit NLRP1-dependent neuronal pyroptosis by suppressing the p38 MAPK pathway and therefore exerted neuroprotective effects against cerebral ischemia- reperfusion injury.

Keywords: Cerebral ischemia-reperfusion injury, curcumin, pyroptosis, NLRP1, blood reperfusion, brain.

[1]
Hsu CC, Kwan GNC, Hapugoda S, Craigie M, Watkins TW, Haacke EM. Susceptibility weighted imaging in acute cerebral ischemia: Review of emerging technical concepts and clinical applications. Neuroradiol J 2017; 30(2): 109-19.
[http://dx.doi.org/10.1177/1971400917690166] [PMID: 28424015]
[2]
Lo WL, Mao YR, Li L, et al. Prospective clinical study of rehabilitation interventions with multisensory interactive training in patients with cerebral infarction: Study protocol for a randomised controlled trial. Trials 2017; 18(1): 173.
[http://dx.doi.org/10.1186/s13063-017-1874-y] [PMID: 28399935]
[3]
Nanetti L, Raffaelli F, Vignini A, et al. Oxidative stress in ischaemic stroke. Eur J Clin Invest 2011; 41(12): 1318-22.
[http://dx.doi.org/10.1111/j.1365-2362.2011.02546.x] [PMID: 21623777]
[4]
Jin R, Yang G, Li G. Inflammatory mechanisms in ischemic stroke: Role of inflammatory cells. J Leukoc Biol 2010; 87(5): 779-89.
[http://dx.doi.org/10.1189/jlb.1109766] [PMID: 20130219]
[5]
Kristián T, Gidö G, Kuroda S, Schütz A, Siesjö BK. Calcium metabolism of focal and penumbral tissues in rats subjected to transient middle cerebral artery occlusion. Exp Brain Res 1998; 120(4): 503-9.
[http://dx.doi.org/10.1007/s002210050424] [PMID: 9655236]
[6]
Wang GH, Lan R, Zhen XD, Zhang W, Xiang J, Cai DF. An- Gong-Niu-Huang Wan protects against cerebral ischemia induced apoptosis in rats: Up-regulation of Bcl-2 and down-regulation of Bax and caspase-3. J Ethnopharmacol 2014; 154(1): 156-62.
[http://dx.doi.org/10.1016/j.jep.2014.03.057] [PMID: 24690773]
[7]
Yang J, Chen M, Cao RY, Li Q, Zhu F. The role of circular RNAs in cerebral ischemic diseases: Ischemic stroke and cerebral ischemia/reperfusion injury. Adv Exp Med Biol 2018; 1087: 309-25.
[http://dx.doi.org/10.1007/978-981-13-1426-1_25] [PMID: 30259377]
[8]
Langhauser F, Göb E, Kraft P, et al. Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis, blood-brain barrier damage, and inflammation. Blood 2012; 120(19): 4082-92.
[http://dx.doi.org/10.1182/blood-2012-06-440057] [PMID: 22936662]
[9]
Ye XH, Wu Y, Guo PP, et al. Lipoxin A4 analogue protects brain and reduces inflammation in a rat model of focal cerebral ischemia reperfusion. Brain Res 2010; 1323: 174-83.
[http://dx.doi.org/10.1016/j.brainres.2010.01.079] [PMID: 20138164]
[10]
Yin J, Zhao F, Chojnacki JE, et al. NLRP3 inflammasome inhibitor ameliorates amyloid pathology in a mouse model of Alzheimer’s disease. Mol Neurobiol 2018; 55(3): 1977-87.
[http://dx.doi.org/10.1007/s12035-017-0467-9] [PMID: 28255908]
[11]
Heneka MT, Kummer MP, Stutz A, et al. NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature 2013; 493(7434): 674-8.
[http://dx.doi.org/10.1038/nature11729] [PMID: 23254930]
[12]
Debye B, Schmülling L, Zhou L, Rune G, Beyer C, Johann S. Neurodegeneration and NLRP3 inflammasome expression in the anterior thalamus of SOD1(G93A) ALS mice. Brain Pathol 2018; 28(1): 14-27.
[http://dx.doi.org/10.1111/bpa.12467] [PMID: 27880990]
[13]
Miao EA, Andersen-Nissen E, Warren SE, Aderem A. TLR5 and Ipaf: dual sensors of bacterial flagellin in the innate immune system. Semin Immunopathol 2007; 29(3): 275-88.
[http://dx.doi.org/10.1007/s00281-007-0078-z] [PMID: 17690885]
[14]
Schroder K, Tschopp J. The inflammasomes. Cell 2010; 140(6): 821-32.
[http://dx.doi.org/10.1016/j.cell.2010.01.040] [PMID: 20303873]
[15]
Hornung V, Latz E. Intracellular DNA recognition. Nat Rev Immunol 2010; 10(2): 123-30.
[http://dx.doi.org/10.1038/nri2690] [PMID: 20098460]
[16]
Miao EA, Mao DP, Yudkovsky N, et al. Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome. Proc Natl Acad Sci USA 2010; 107(7): 3076-80.
[http://dx.doi.org/10.1073/pnas.0913087107] [PMID: 20133635]
[17]
Fink SL, Bergsbaken T, Cookson BT. Anthrax lethal toxin and Salmonella elicit the common cell death pathway of caspase-1-dependent pyroptosis via distinct mechanisms. Proc Natl Acad Sci USA 2008; 105(11): 4312-7.
[http://dx.doi.org/10.1073/pnas.0707370105] [PMID: 18337499]
[18]
Boyden ED, Dietrich WF. Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nat Genet 2006; 38(2): 240-4.
[http://dx.doi.org/10.1038/ng1724] [PMID: 16429160]
[19]
Ding J, Wang K, Liu W, et al. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature 2016; 535(7610): 111-6.
[http://dx.doi.org/10.1038/nature18590] [PMID: 27281216]
[20]
Sborgi L, Rühl S, Mulvihill E, et al. GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death. EMBO J 2016; 35(16): 1766-78.
[http://dx.doi.org/10.15252/embj.201694696] [PMID: 27418190]
[21]
Kummer JA, Broekhuizen R, Everett H, et al. Inflammasome components NALP 1 and 3 show distinct but separate expression profiles in human tissues suggesting a site-specific role in the inflammatory response. J Histochem Cytochem 2007; 55(5): 443-52.
[http://dx.doi.org/10.1369/jhc.6A7101.2006] [PMID: 17164409]
[22]
Fann DY-W, Lee SY, Manzanero S, et al. Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke. Cell Death Dis 2013; 4(9): e790-90.
[http://dx.doi.org/10.1038/cddis.2013.326] [PMID: 24008734]
[23]
Meng XF, Wang XL, Tian XJ, et al. Nod-like receptor protein 1 inflammasome mediates neuron injury under high glucose. Mol Neurobiol 2014; 49(2): 673-84.
[http://dx.doi.org/10.1007/s12035-013-8551-2] [PMID: 24014157]
[24]
Tian Y, Liu M, Mao-Ying Q-L, et al. Early single Aspirin-triggered Lipoxin blocked morphine anti-nociception tolerance through inhibiting NALP1 inflammasome: Involvement of PI3k/Akt signaling pathway. Brain Behav Immun 2015; 50: 63-77.
[http://dx.doi.org/10.1016/j.bbi.2015.06.016] [PMID: 26162710]
[25]
Huang Z, Ye B, Dai Z, et al. Curcumin inhibits autophagy and apoptosis in hypoxia/reoxygenation-induced myocytes. Mol Med Rep 2015; 11(6): 4678-84.
[http://dx.doi.org/10.3892/mmr.2015.3322] [PMID: 25673156]
[26]
Nehra S, Bhardwaj V, Bansal A, Saraswat D. Nanocurcumin accords protection against acute hypobaric hypoxia induced lung injury in rats. J Physiol Biochem 2016; 72(4): 763-79.
[http://dx.doi.org/10.1007/s13105-016-0515-3] [PMID: 27534650]
[27]
Hou Y, Wang J, Feng J. The neuroprotective effects of curcumin are associated with the regulation of the reciprocal function between autophagy and HIF-1α in cerebral ischemia-reperfusion injury. Drug Des Devel Ther 2019; 13: 1135-44.
[http://dx.doi.org/10.2147/DDDT.S194182] [PMID: 31040648]
[28]
Xie CJ, Gu AP, Cai J, Wu Y, Chen RC. Curcumin protects neural cells against ischemic injury in N2a cells and mouse brain with ischemic stroke. Brain Behav 2018; 8(2): e00921.
[http://dx.doi.org/10.1002/brb3.921] [PMID: 29484272]
[29]
Wu MY, Yiang GT, Liao WT, et al. Current mechanistic concepts in ischemia and reperfusion injury. Cell Physiol Biochem 2018; 46(4): 1650-67.
[http://dx.doi.org/10.1159/000489241] [PMID: 29694958]
[30]
Hewlings SJ, Kalman DS. Curcumin: A review of its effects on human health. Foods 2017; 6(10): E92.
[http://dx.doi.org/10.3390/foods6100092] [PMID: 29065496]
[31]
Daverey A, Agrawal SK. Curcumin alleviates oxidative stress and mitochondrial dysfunction in astrocytes. Neuroscience 2016; 333: 92-103.
[http://dx.doi.org/10.1016/j.neuroscience.2016.07.012] [PMID: 27423629]
[32]
Loganes C, Lega S, Bramuzzo M, et al. Curcumin anti-apoptotic action in a model of intestinal epithelial inflammatory damage. Nutrients 2017; 9(6): 578.
[http://dx.doi.org/10.3390/nu9060578] [PMID: 28587282]
[33]
Yin H, Guo Q, Li X, et al. Curcumin suppresses IL-1β secretion and prevents inflammation through inhibition of the NLRP3 inflammasome. J Immunol 2018; 200(8): 2835-46.
[http://dx.doi.org/10.4049/jimmunol.1701495] [PMID: 29549176]
[34]
Kovarova M, Hesker PR, Jania L, et al. NLRP1-dependent pyroptosis leads to acute lung injury and morbidity in mice. J Immunol 2012; 189(4): 2006-16.
[http://dx.doi.org/10.4049/jimmunol.1201065] [PMID: 22753929]
[35]
Tan CC, Zhang JG, Tan MS, et al. NLRP1 inflammasome is activated in patients with medial temporal lobe epilepsy and contributes to neuronal pyroptosis in amygdala kindling-induced rat model. J Neuroinflammation 2015; 12: 18.
[http://dx.doi.org/10.1186/s12974-014-0233-0] [PMID: 25626361]
[36]
An P, Xie J, Qiu S, et al. Hispidulin exhibits neuroprotective activities against cerebral ischemia reperfusion injury through suppressing NLRP3-mediated pyroptosis. Life Sci 2019; 232: 116599.
[http://dx.doi.org/10.1016/j.lfs.2019.116599] [PMID: 31247210]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy