Tetrandrine alleviates cerebral ischemia/reperfusion injury by suppressing NLRP3 inflammasome activation via Sirt-1.
Cerebral ischemia
Ischemia/reperfusion injury
NLRP3 inflammasome
Silent information regulator-1
Tetrandrine
Journal
PeerJ
ISSN: 2167-8359
Titre abrégé: PeerJ
Pays: United States
ID NLM: 101603425
Informations de publication
Date de publication:
2020
2020
Historique:
received:
06
01
2020
accepted:
01
04
2020
entrez:
19
5
2020
pubmed:
19
5
2020
medline:
19
5
2020
Statut:
epublish
Résumé
Tetrandrine (Tet) has been reported to have anti-inflammatory effects and protect from the ischemic strokes. The NLRP3 inflammasome plays a key role in cerebral ischemia/reperfusion (I/R)-induced inflammatory lesions. However, the molecular mechanisms of Tet related to the progression of cerebral ischemia are still unclear. Therefore, the aim of this study was to investigate the possible effects of Tet on cerebral ischemia and the related mechanisms involved in NLRP3 inflammasome. C57BL/6J mice used as a cerebral I/R injury model underwent middle cerebral artery occlusion (MCAO) for 2 h following reperfusion for 24 h. Tet (30 mg/kg/day, Tet significantly reduced the neurological deficits, infarction volume, and cerebral water content in MCAO mice. Moreover, it inhibited I/R-induced over expression of NLRP3, cleaved caspase-1, interleukin (IL)-1β, IL-18, and Sirt-1. Sirt-1 knockdown with siRNA greatly blocked the Tet-induced reduction of neurological severity score and infarct volume, and reversed the inhibition of NLRP3 inflammasome activation. Our results demonstrate that Tet has benefits for cerebral I/R injury, which are partially related to the suppression of NLRP3 inflammasome activation via upregulating Sirt-1.
Sections du résumé
BACKGROUND & AIMS
OBJECTIVE
Tetrandrine (Tet) has been reported to have anti-inflammatory effects and protect from the ischemic strokes. The NLRP3 inflammasome plays a key role in cerebral ischemia/reperfusion (I/R)-induced inflammatory lesions. However, the molecular mechanisms of Tet related to the progression of cerebral ischemia are still unclear. Therefore, the aim of this study was to investigate the possible effects of Tet on cerebral ischemia and the related mechanisms involved in NLRP3 inflammasome.
METHODS
METHODS
C57BL/6J mice used as a cerebral I/R injury model underwent middle cerebral artery occlusion (MCAO) for 2 h following reperfusion for 24 h. Tet (30 mg/kg/day,
RESULTS
RESULTS
Tet significantly reduced the neurological deficits, infarction volume, and cerebral water content in MCAO mice. Moreover, it inhibited I/R-induced over expression of NLRP3, cleaved caspase-1, interleukin (IL)-1β, IL-18, and Sirt-1. Sirt-1 knockdown with siRNA greatly blocked the Tet-induced reduction of neurological severity score and infarct volume, and reversed the inhibition of NLRP3 inflammasome activation.
CONCLUSION
CONCLUSIONS
Our results demonstrate that Tet has benefits for cerebral I/R injury, which are partially related to the suppression of NLRP3 inflammasome activation via upregulating Sirt-1.
Identifiants
pubmed: 32419986
doi: 10.7717/peerj.9042
pii: 9042
pmc: PMC7211409
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e9042Informations de copyright
©2020 Wang et al.
Déclaration de conflit d'intérêts
The authors declare there are no competing interests.
Références
Arch Toxicol. 2019 Apr;93(4):965-986
pubmed: 30796460
Inflamm Regen. 2017 Sep 11;37:18
pubmed: 29259717
Neurosci Lett. 2000 Jul 7;288(1):61-5
pubmed: 10869816
Int Immunopharmacol. 2016 Nov;40:492-500
pubmed: 27769021
Neurochem Res. 2013 Sep;38(9):1871-9
pubmed: 23780673
Inflamm Res. 2018 Jan;67(1):57-65
pubmed: 28956063
Neurosci Lett. 2015 Jul 23;600:182-7
pubmed: 26071904
Trends Pharmacol Sci. 2004 Mar;25(3):120-3
pubmed: 15058281
World J Gastroenterol. 2003 Jan;9(1):155-9
pubmed: 12508373
Int J Nurs Knowl. 2019 Nov 7;:
pubmed: 31697041
Molecules. 2011 Sep 16;16(9):8020-32
pubmed: 21926947
Autophagy. 2017 May 4;13(5):914-927
pubmed: 28318352
J Neuroinflammation. 2017 Jul 24;14(1):143
pubmed: 28738820
Anticancer Res. 2009 Aug;29(8):3163-71
pubmed: 19661330
Antioxid Redox Signal. 2018 Sep 10;29(8):749-791
pubmed: 29256638
Nature. 2018 Dec;564(7734):71-76
pubmed: 30487600
Int Immunopharmacol. 2018 Jan;54:78-85
pubmed: 29107864
J Surg Res. 2015 Jul;197(1):191-200
pubmed: 25930168
J Pediatr Surg. 2009 Nov;44(11):2145-52
pubmed: 19944224
J Neuroendocrinol. 2018 Feb;30(2):
pubmed: 28477436
Int J Cancer. 2009 May 15;124(10):2260-9
pubmed: 19165864
J Pineal Res. 2015 Jan;58(1):61-70
pubmed: 25401748
Life Sci. 2001 Aug 10;69(12):1429-39
pubmed: 11531166
Exp Ther Med. 2018 Sep;16(3):2670-2676
pubmed: 30186500
Int Immunopharmacol. 2019 Mar;68:234-241
pubmed: 30703695
J Ethnopharmacol. 2015 Aug 22;172:108-17
pubmed: 26117533
Zhongguo Yao Li Xue Bao. 1995 Mar;16(2):145-8
pubmed: 7597916
Lab Invest. 2014 Jan;94(1):52-62
pubmed: 24166187
Autophagy. 2019 Sep;15(9):1645-1647
pubmed: 31177914
J Stroke Cerebrovasc Dis. 2018 Jun;27(6):1697-1704
pubmed: 29525080
Front Neurol. 2017 Sep 07;8:467
pubmed: 28936196
Mol Neurobiol. 2016 Oct;53(8):5468-79
pubmed: 26452362
World J Surg. 2004 Jun;28(6):620-4
pubmed: 15366756
Int Immunopharmacol. 2017 Sep;50:208-215
pubmed: 28683365
Eur J Pharmacol. 2017 Oct 15;813:153-160
pubmed: 28822855
Brain Res. 2019 Nov 15;1723:146391
pubmed: 31421130
J Mol Neurosci. 2019 Nov;69(3):411-418
pubmed: 31267316