Login Register Cart 0
Generic placeholder image

Current Neurovascular Research

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

The Mechanism of Astragaloside IV in NOD-like Receptor Family Pyrin Domain Containing 3 Inflammasome-mediated Pyroptosis after Intracerebral Hemorrhage

Author(s): Honggang Wu, Shu Chen, Guoliang You, Bo Lei, Li Chen, Jiachuan Wu, Niandong Zheng and Chao You*

Volume 21, Issue 1, 2024

Published on: 22 February, 2024

Page: [74 - 85] Pages: 12

DOI: 10.2174/0115672026295640240212095049

Price: $65

conference banner
Abstract

Background: Intracerebral hemorrhage (ICH) is one of the most common subtypes of stroke.

Objectives: This study aimed to investigate the mechanism of Astragaloside IV (AS-IV) on inflammatory injury after ICH.

Methods: The ICH model was established by the injection of collagenase and treated with ASIV (20 mg/kg or 40 mg/kg). The neurological function, water content of the bilateral cerebral hemisphere and cerebellum, and pathological changes in brain tissue were assessed. The levels of interleukin-1 beta (IL-1β), IL-18, tumor necrosis factor-alpha, interferon-gamma, and IL-10 were detected by enzyme-linked immunosorbent assay. The levels of Kruppel-like factor 2 (KLF2), NOD-like receptor family pyrin domain containing 3 (NLRP3), GSDMD-N, and cleaved-caspase-1 were detected by reverse transcription-quantitative polymerase chain reaction and Western blot assay. The binding relationship between KLF2 and NLRP3 was verified by chromatin-immunoprecipitation and dual-luciferase assays. KLF2 inhibition or NLRP3 overexpression was achieved in mice to observe pathological changes.

Results: The decreased neurological function, increased water content, severe pathological damage, and inflammatory response were observed in mice after ICH, with increased levels of NLRP3/GSDMD-N/cleaved-caspase-1/IL-1β/IL-18 and poorly-expressed KLF2 in brain tissue. After AS-IV treatment, the neurological dysfunction, high brain water content, inflammatory response, and pyroptosis were alleviated, while KLF2 expression was increased. KLF2 bonded to the NLRP3 promoter region and inhibited its transcription. Down-regulation of KLF2 or upregulation of NLRP3 reversed the effect of AS-IV on inhibiting pyroptosis and reducing inflammatory injury in mice after ICH.

Conclusion: AS-IV inhibited NLRP3-mediated pyroptosis by promoting KLF2 expression and alleviated inflammatory injury in mice after ICH.

Keywords: KLF2, NLRP3, Intracerebral hemorrhage, astragaloside IV, pyroptosis, inflammatory injury, the promoter, hematoxylin and eosin.

« Previous
[1]
Wilkinson DA, Pandey AS, Thompson BG, Keep RF, Hua Y, Xi G. Injury mechanisms in acute intracerebral hemorrhage. Neuropharmacology 2018; 134(Pt B): 240.: 8.
[http://dx.doi.org/10.1016/j.neuropharm.2017.09.033] [PMID: 28947377]
[2]
Tschoe C, Bushnell CD, Duncan PW, Alexander-Miller MA, Wolfe SQ. Neuroinflammation after Intracerebral Hemorrhage and Potential Therapeutic Targets. J Stroke 2020; 22(1): 29-46.
[http://dx.doi.org/10.5853/jos.2019.02236] [PMID: 32027790]
[3]
Ekkert A, Šliachtenko A, Utkus A, Jatužis D. Intracerebral hemorrhage genetics. Genes (Basel) 2022; 13(7): 1250.
[http://dx.doi.org/10.3390/genes13071250] [PMID: 35886033]
[4]
Pinho J, Costa AS, Araújo JM, Amorim JM, Ferreira C. Intracerebral hemorrhage outcome: A comprehensive update. J Neurol Sci 2019; 398: 54-66.
[http://dx.doi.org/10.1016/j.jns.2019.01.013] [PMID: 30682522]
[5]
Al-Kawaz MN, Hanley DF, Ziai W. Advances in therapeutic approaches for spontaneous intracerebral hemorrhage. Neurotherapeutics 2020; 17(4): 1757-67.
[http://dx.doi.org/10.1007/s13311-020-00902-w] [PMID: 32720246]
[6]
Wang S, Yuan YH, Chen NH, Wang HB. The mechanisms of NLRP3 inflammasome/pyroptosis activation and their role in Parkinson’s disease. Int Immunopharmacol 2019; 67: 458-64.
[http://dx.doi.org/10.1016/j.intimp.2018.12.019] [PMID: 30594776]
[7]
Song D, Yeh CT, Wang J, Guo F. Perspectives on the mechanism of pyroptosis after intracerebral hemorrhage. Front Immunol 2022; 13: 989503.
[http://dx.doi.org/10.3389/fimmu.2022.989503] [PMID: 36131917]
[8]
Ran Y, Su W, Gao F, et al. Curcumin ameliorates white matter injury after ischemic stroke by inhibiting microglia/macrophage pyroptosis through NF-κB suppression and NLRP3 inflammasome inhibition. Oxid Med Cell Longev 2021; 2021: 1-25.
[http://dx.doi.org/10.1155/2021/1552127] [PMID: 34630845]
[9]
Shao BZ, Xu ZQ, Han BZ, Su DF, Liu C. NLRP3 inflammasome and its inhibitors: A review. Front Pharmacol 2015; 6: 262.
[http://dx.doi.org/10.3389/fphar.2015.00262] [PMID: 26594174]
[10]
Wang T, Nowrangi D, Yu L, et al. Activation of dopamine D1 receptor decreased NLRP3-mediated inflammation in intracerebral hemorrhage mice. J Neuroinflammation 2018; 15(1): 2.
[http://dx.doi.org/10.1186/s12974-017-1039-7] [PMID: 29301581]
[11]
Gu L, Sun M, Li R, et al. Didymin suppresses microglia pyroptosis and neuroinflammation through the Asc/Caspase-1/GSDMD pathway following experimental intracerebral hemorrhage. Front Immunol 2022; 13: 810582.
[http://dx.doi.org/10.3389/fimmu.2022.810582] [PMID: 35154128]
[12]
Xiao L, Wang M, Shi Y, et al. Secondary white matter injury mediated by neuroinflammation after intracerebral hemorrhage and promising therapeutic strategies of targeting the NLRP3 inflammasome. Curr Neuropharmacol 2023; 21(3): 669-86.
[http://dx.doi.org/10.2174/1570159X20666220830115018] [PMID: 36043798]
[13]
Kang X, Su S, Hong W, Geng W, Tang H. Research progress on the ability of astragaloside IV to protect the brain against ischemia-reperfusion injury. Front Neurosci 2021; 15: 755902.
[http://dx.doi.org/10.3389/fnins.2021.755902] [PMID: 34867166]
[14]
Huang K, Yu Y, Liu S, et al. A single, acute astragaloside iv therapy protects cardiomyocyte through attenuating superoxide anion-mediated accumulation of autophagosomes in myocardial ischemia-reperfusion injury. Front Pharmacol 2021; 12: 642925.
[http://dx.doi.org/10.3389/fphar.2021.642925] [PMID: 34349641]
[15]
Zhu Y, Qian X, Li J, et al. Astragaloside-IV protects H9C2(2-1) cardiomyocytes from high glucose-induced injury via miR-34a-mediated autophagy pathway. Artif Cells Nanomed Biotechnol 2019; 47(1): 4172-81.
[http://dx.doi.org/10.1080/21691401.2019.1687492] [PMID: 31713440]
[16]
Song Z, Wei D, Chen Y, et al. Association of astragaloside IV-inhibited autophagy and mineralization in vascular smooth muscle cells with lncRNA H19 and DUSP5-mediated ERK signaling. Toxicol Appl Pharmacol 2019; 364: 45-54.
[http://dx.doi.org/10.1016/j.taap.2018.12.002] [PMID: 30529164]
[17]
Shi YH, Zhang XL, Ying PJ, et al. Neuroprotective effect of astragaloside IV on cerebral ischemia/reperfusion injury rats through Sirt1/Mapt pathway. Front Pharmacol 2021; 12: 639898.
[http://dx.doi.org/10.3389/fphar.2021.639898] [PMID: 33841157]
[18]
Ma Y, Qiao G, Yin Y, Zhang Y, Yu Y, Yu X. Protective effects of astragaloside IV on delayed cerebral vasospasm in an experimental rat model of subarachnoid hemorrhage. World Neurosurg 2018; 118: e443-8.
[http://dx.doi.org/10.1016/j.wneu.2018.06.212] [PMID: 29981464]
[19]
Zheng Y, Li R, Zhou Y, Zhang S, Fan X. Investigation on the potential targets of Astragaloside IV against intracerebral hemorrhage based on network pharmacology and experimental validation. Bioorg Chem 2022; 127: 105975.
[http://dx.doi.org/10.1016/j.bioorg.2022.105975] [PMID: 35728292]
[20]
Su Y, Yin X, Huang X, Guo Q, Ma M, Guo L. The BCL2/BAX/ROS pathway is involved in the inhibitory effect of astragaloside IV on pyroptosis in human umbilical vein endothelial cells. Pharm Biol 2022; 60(1): 1812-8.
[http://dx.doi.org/10.1080/13880209.2022.2101668] [PMID: 36121248]
[21]
Turpaev KT. Transcription factor KLF2 and its role in the regulation of inflammatory processes. Biochemistry 2020; 85(1): 54-67.
[http://dx.doi.org/10.1134/S0006297920010058] [PMID: 32079517]
[22]
Lu T, Peng S, Wang J, et al. Fraxinellone ameliorates intracerebral hemorrhage-induced secondary brain injury by regulating Krüppel-like transcription factor 2 expression in rats. Brain Res Bull 2021; 177: 340-51.
[http://dx.doi.org/10.1016/j.brainresbull.2021.10.018] [PMID: 34717966]
[23]
Zhang X, Liu T, Xu S, et al. A pro-inflammatory mediator USP11 enhances the stability of p53 and inhibits KLF2 in intracerebral hemorrhage. Mol Ther Methods Clin Dev 2021; 21: 681-92.
[http://dx.doi.org/10.1016/j.omtm.2021.01.015] [PMID: 34141823]
[24]
Jin H, Zhu Y, Wang X, et al. BDNF corrects NLRP3 inflammasome-induced pyroptosis and glucose metabolism reprogramming through KLF2/HK1 pathway in vascular endothelial cells. Cell Signal 2021; 78: 109843.
[http://dx.doi.org/10.1016/j.cellsig.2020.109843] [PMID: 33253911]
[25]
Jones-Bolin S. Guidelines for the care and use of laboratory animals in biomedical research. Curr Protoc Pharmacol Appendix 2012; 4(Appendix): 4B.
[26]
Chen S, Peng J, Sherchan P, et al. TREM2 activation attenuates neuroinflammation and neuronal apoptosis via PI3K/Akt pathway after intracerebral hemorrhage in mice. J Neuroinflammation 2020; 17(1): 168.
[http://dx.doi.org/10.1186/s12974-020-01853-x] [PMID: 32466767]
[27]
Kopaladze RA. Methods for the euthanasia of experimental animals--the ethics, esthetics and personnel safety. Usp Fiziol Nauk 2000; 31(3): 79-90.
[PMID: 11042900]
[28]
Wang CJ, Qu CQ, Zhang J, Fu PC, Guo SG, Tang RH. Lingo-1 inhibited by RNA interference promotes functional recovery of experimental autoimmune encephalomyelitis. Anat Rec (Hoboken) 2014; 297(12): 2356-63.
[http://dx.doi.org/10.1002/ar.22988] [PMID: 25045138]
[29]
Li Z, Wang B, Kan Z, et al. Progesterone increases circulating endothelial progenitor cells and induces neural regeneration after traumatic brain injury in aged rats. J Neurotrauma 2012; 29(2): 343-53.
[http://dx.doi.org/10.1089/neu.2011.1807] [PMID: 21534727]
[30]
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Method Methods 2001; 25(4): 402-8.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[31]
Castro-Mondragon JA, Riudavets-Puig R, Rauluseviciute I, et al. JASPAR 2022: The 9th release of the open-access database of transcription factor binding profiles. Nucleic Acids Res 2022; 50(D1): D165-73.
[http://dx.doi.org/10.1093/nar/gkab1113] [PMID: 34850907]
[32]
Hostettler IC, Seiffge DJ, Werring DJ. Intracerebral hemorrhage: An update on diagnosis and treatment. Expert Rev Neurother 2019; 19(7): 679-94.
[http://dx.doi.org/10.1080/14737175.2019.1623671] [PMID: 31188036]
[33]
Zeng P, Wang XM, Su HF, et al. Protective effects of Da-cheng-qi decoction in rats with intracerebral hemorrhage. Phytomedicine 2021; 90: 153630.
[http://dx.doi.org/10.1016/j.phymed.2021.153630] [PMID: 34217968]
[34]
Jin ZL, Gao WY, Liao SJ, et al. Paeonol inhibits the progression of intracerebral haemorrhage by mediating the HOTAIR/UPF1/ACSL4 axis. ASN Neuro 2021; •••: 13.
[http://dx.doi.org/10.1177/17590914211010647] [PMID: 33906483]
[35]
Duan L, Zhang Y, Yang Y, et al. Baicalin inhibits ferroptosis in intracerebral hemorrhage. Front Pharmacol 2021; 12: 629379.
[http://dx.doi.org/10.3389/fphar.2021.629379] [PMID: 33815110]
[36]
Li Z, Li Y, Han J, et al. Formyl peptide receptor 1 signaling potentiates inflammatory brain injury. Sci Transl Med 2021; 13(605): eabe9890.
[http://dx.doi.org/10.1126/scitranslmed.abe9890] [PMID: 34349037]
[37]
Liu W, Rong Y, Wang J, et al. Exosome-shuttled miR-216a-5p from hypoxic preconditioned mesenchymal stem cells repair traumatic spinal cord injury by shifting microglial M1/M2 polarization. J Neuroinflammation 2020; 17(1): 47.
[http://dx.doi.org/10.1186/s12974-020-1726-7] [PMID: 32019561]
[38]
Wang X, Gao F, Xu W, Cao Y, Wang J, Zhu G. Depichering the effects of astragaloside IV on AD-like phenotypes: A systematic and experimental investigation. Oxid Med Cell Longev 2021; 2021: 1-21.
[http://dx.doi.org/10.1155/2021/1020614] [PMID: 34616501]
[39]
Qu S, Liu Z, Wang B. EZH2 is involved in psoriasis progression by impairing miR-125a-5p inhibition of SFMBT1 and leading to inhibition of the TGFβ/SMAD pathway. Ther Adv Chronic Dis 2021; •••: 12.
[http://dx.doi.org/10.1177/2040622320987348] [PMID: 33948156]
[40]
Jha P, Das H. KLF2 in regulation of NF-κB-mediated immune cell function and inflammation. Int J Mol Sci 2017; 18(11): 2383.
[http://dx.doi.org/10.3390/ijms18112383] [PMID: 29125549]
[41]
Wu F, Li C. KLF2 up-regulates IRF4/HDAC7 to protect neonatal rats from hypoxic-ischemic brain damage. Cell Death Discov 2022; 8(1): 41.
[http://dx.doi.org/10.1038/s41420-022-00813-z] [PMID: 35091544]
[42]
Lei L, Chen M, Wang C, et al. Trichostatin D as a novel KLF2 activator attenuates TNFα-induced endothelial inflammation. Int J Mol Sci 2022; 23(21): 13477.
[http://dx.doi.org/10.3390/ijms232113477] [PMID: 36362263]
[43]
Zhuang T, Liu J, Chen X, et al. Endothelial foxp1 suppresses atherosclerosis via modulation of Nlrp3 inflammasome activation. Circ Res 2019; 125(6): 590-605.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.314402] [PMID: 31318658]
[44]
Poznyak AV, Melnichenko AA, Wetzker R, Gerasimova EV, Orekhov AN. NLPR3 inflammasomes and their significance for atherosclerosis. Biomedicines 2020; 8(7): 205.
[http://dx.doi.org/10.3390/biomedicines8070205] [PMID: 32664349]
[45]
Chen Y, Meng J, Bi F, et al. NEK7 regulates NLRP3 inflammasome activation and neuroinflammation post-traumatic brain injury. Front Mol Neurosci 2019; 12: 202.
[http://dx.doi.org/10.3389/fnmol.2019.00202] [PMID: 31555089]
[46]
Fan Y-H, He Z-Y, Zheng W-X, Hu L-T, Wang B-Y. Exosomal miR-23b from bone marrow mesenchymal stem cells alleviates oxidative stress and pyroptosis after intracerebral hemorrhage. Neural Regen Res 2023; 18(3): 560-7.
[http://dx.doi.org/10.4103/1673-5374.346551] [PMID: 36018178]
[47]
Wang X, Huo R, Liang Z, et al. Simvastatin inhibits NLRP3 inflammasome activation and ameliorates lung injury in hyperoxia-induced bronchopulmonary dysplasia via the KLF2-mediated mechanism. Oxid Med Cell Longev 2022; 2022: 1-15.
[http://dx.doi.org/10.1155/2022/8336070] [PMID: 35509841]
[48]
Li M, Li H, Fang F, Deng X, Ma S. Astragaloside IV attenuates cognitive impairments induced by transient cerebral ischemia and reperfusion in mice via anti-inflammatory mechanisms. Neurosci Lett 2017; 639: 114-9.
[http://dx.doi.org/10.1016/j.neulet.2016.12.046] [PMID: 28011393]

Rights & Permissions Print Cite
Article Metrics
21
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy