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Ischaemic stroke possesses the characteristics of high incidence, high disability and high mortality. Icariin (ICA) is a flavonoid extracted from the traditional Chinese medicine Epimedium. The protective effect of ICA on ischaemic stroke is worthy of further study. In this study, male Sprague-Dawley rats were randomly divided into the following seven groups: sham, model, ICA low-dose (10 mg/kg), ICA medium-dose (20 mg/kg), ICA high-dose (40 mg/kg), positive control drug (12 mg/kg nimodipine) and endoplasmic reticulum stress induction (0.16 mg/kg tunicamycin) groups. The model of cerebral ischaemia-reperfusion injury in the rats, including 2 h ischaemia and 24 h reperfusion, was accomplished by applying the method of transient middle cerebral artery occlusion (MCAO). At 24 h reperfusion, neurological deficits, brain water content, pathological damage of brain tissues, the expression of inflammation-related targets, and the signal pathway-related proteins were explored. Compared with the model group, ICA significantly improved neurological deficits, brain oedema and pathological damage after MCAO. In addition, ICA increased neuron survival, reduced microglial activation and expression of IL-1β, alleviating the inflammatory damage caused by ischaemic stroke. Moreover, ICA suppressed the expressions of glucose-regulated protein 78 (GRP78), inositol requiring enzyme-1 α (IRE1α), phospho-IRE1α (p-IRE1α), protein kinase RNA-like ER kinase (PERK), phospho-PERK (p-PERK), spliced XBP1 (XBP1s), unspliced XBP1 (XBP1u), thioredoxin-interacting protein (TXNIP), NLRP3, and caspase-1. These results suggested that ICA offers neuroprotection against ischaemic stroke by inhibiting ER stress-mediated inflammation.

Titel:	Icariin attenuates ischaemic stroke through suppressing inflammation mediated by endoplasmic reticulum stress signalling pathway in rats.
Autor/in / Beteiligte Person:	Zheng, J ; Liao, Y ; Xu, Y ; Mo, Z
Link:	Zum Volltext
Zeitschrift:	Clinical and experimental pharmacology & physiology, Jg. 49 (2022-07-01), Heft 7, S. 719-730
Veröffentlichung:	Oxford, England : Wiley-Blackwell ; <i>Original Publication</i>: Oxford, Blackwell Scientific Publications., 2022
Medientyp:	academicJournal
ISSN:	1440-1681 (electronic)
DOI:	10.1111/1440-1681.13645
Schlagwort:	Animals Apoptosis Cell Cycle Proteins metabolism Endoplasmic Reticulum Stress Endoribonucleases Flavonoids Infarction, Middle Cerebral Artery complications Infarction, Middle Cerebral Artery drug therapy Inflammation drug therapy Male Protein Serine-Threonine Kinases Rats Rats, Sprague-Dawley Signal Transduction Brain Ischemia metabolism Ischemic Stroke Stroke drug therapy
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Clin Exp Pharmacol Physiol] 2022 Jul; Vol. 49 (7), pp. 719-730. <i>Date of Electronic Publication: </i>2022 May 02. MeSH Terms: Brain Ischemia* / metabolism ; Ischemic Stroke* ; Stroke* / drug therapy ; Animals ; Apoptosis ; Cell Cycle Proteins / metabolism ; Endoplasmic Reticulum Stress ; Endoribonucleases ; Flavonoids ; Infarction, Middle Cerebral Artery / complications ; Infarction, Middle Cerebral Artery / drug therapy ; Inflammation / drug therapy ; Male ; Protein Serine-Threonine Kinases ; Rats ; Rats, Sprague-Dawley ; Signal Transduction References: Wu S, Wu B, Liu M, et al. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol. 2019;18(4):394-405. ; Zhang W, Tian T, Gong SX, et al. Microglia-associated neuroinflammation is a potential therapeutic target for ischemic stroke. 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Icariside II protects against cerebral ischemia-reperfusion injury in rats via nuclear factor-kappaB inhibition and peroxisome proliferator-activated receptor up-regulation. Neurochem Int. 2016;96:56-61. ; Sun X, Liu H, Sun Z, et al. Acupuncture protects against cerebral ischemia-reperfusion injury via suppressing endoplasmic reticulum stress-mediated autophagy and apoptosis. Mol Med. 2020;26(1):105. Contributed Indexing: Keywords: Icariin; endoplasmic reticulum stress; inflammation; ischaemic stroke Substance Nomenclature: 0 (Cell Cycle Proteins) ; 0 (Flavonoids) ; 0 (TXNIP protein, rat) ; EC 2.7.11.1 (Protein Serine-Threonine Kinases) ; EC 3.1.- (Endoribonucleases) ; VNM47R2QSQ (icariin) Entry Date(s): Date Created: 20220422 Date Completed: 20220616 Latest Revision: 20220821 Update Code: 20240513

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Icariin attenuates ischaemic stroke through suppressing inflammation mediated by endoplasmic reticulum stress signalling pathway in rats.