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Therapeutic hypothermia (TH) is a promising neuroprotective agent for treating stroke. However, its clinical application was limited by the impractical duration. Icariin (ICA) were reported to have therapeutic effect on cerebral ischemia. In this research, our aim was to investigate whether the combination of TH and ICA had better neuroprotective effects on ischemic stroke. An ischemia-reperfusion rat model was established and treated with mild hypothermia, ICA or JSH-23 (inhibitor of NF-κB). Thermistor probe, 2'3'5'-triphenyl tetrazolium chloride (TTC), 5/12-score system, and ELISA were used to detect temperature (rectum, cortex, striatum), infarct volume, neurological deficit, and cerebral cell death of these rats. The expressions of tumor necrosis factor (TNF)-α, Interleukin- 6 (IL-6), nuclear factor-kappa B (NF-κB), nuclear factor erythroid2-related factor (Nrf2), peroxisome proliferator activated receptor gamma (PPARα), PPARγ, Janus kinase 2 (JAK2), p-JAK2, signal transducers and activators of transduction-3 (STAT3), and p-STAT3 were detected by Western blot or q-PCR. Mild hypothermia, ICA, and JSH-23 reduced the cerebral infarct volume, neurological deficit, cerebral cell death of rats, downregulated the expressions of TNF-α, IL-6, C-Caspase 3 and Bax, and the activation of PPARs/Nrf2/NF-κB and JAK2/STAT3 pathways, but elevated the expression of Bcl-2. ICA promoted the effect of mild hypothermia on infarct volume, neurological deficit, and cerebral cell death. Moreover, ICA also enhanced the regulatory effect of mild hypothermia on apoptosis/inflammation factors expressions and activation of PPARs/Nrf2/NF-κB and JAK2/STAT3 pathways. ICA could promote mild hypothermia-induced neuroprotection by inhibiting the activation of NF-κB through the PPARs/Nrf2/NF-κB and JAK2/STAT3/NF-κB pathways in experimental stroke.

Titel:	Icariin enhance mild hypothermia-induced neuroprotection via inhibiting the activation of NF-κB in experimental ischemic stroke.
Autor/in / Beteiligte Person:	Dai, M ; Chen, B ; Wang, X ; Gao, C ; Yu, H
Link:	Zum Volltext
Zeitschrift:	Metabolic brain disease, Jg. 36 (2021-10-01), Heft 7, S. 1779-1790
Veröffentlichung:	2005- : Amsterdam : Springer ; <i>Original Publication</i>: New York : Plenum, c1986-, 2021
Medientyp:	academicJournal
ISSN:	1573-7365 (electronic)
DOI:	10.1007/s11011-021-00731-6
Schlagwort:	Animals Flavonoids NF-kappa B metabolism Neuroprotection Rats Hypothermia Ischemic Stroke Reperfusion Injury metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Metab Brain Dis] 2021 Oct; Vol. 36 (7), pp. 1779-1790. <i>Date of Electronic Publication: </i>2021 May 12. MeSH Terms: Hypothermia* ; Ischemic Stroke* ; Reperfusion Injury* / metabolism ; Animals ; Flavonoids ; NF-kappa B / metabolism ; Neuroprotection ; Rats References: Aljehani AA, Albadr NA, Eid BG, Abdel-Naim AB (2020) Icariin enhances AMP-activated protein kinase and prevents high fructose and high salt-induced metabolic syndrome in rats. Saudi Pharm J 28:1309–1316. https://doi.org/10.1016/j.jsps.2020.08.021. (PMID: 10.1016/j.jsps.2020.08.021332506407679472) ; An H et al (2017) Phenothiazines enhance mild hypothermia-induced Neuroprotection via PI3K/Akt regulation in experimental stroke. Sci Rep 7:7469. https://doi.org/10.1038/s41598-017-06752-5. 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(PMID: 10.1016/j.cbd.2020.10075633197858) Contributed Indexing: Keywords: Icariin; Ischemic stroke; JAK2/STAT3; Mild hypothermia; Nrf2/NF-κB Substance Nomenclature: 0 (Flavonoids) ; 0 (NF-kappa B) ; VNM47R2QSQ (icariin) Entry Date(s): Date Created: 20210512 Date Completed: 20220407 Latest Revision: 20220407 Update Code: 20231215

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Icariin enhance mild hypothermia-induced neuroprotection via inhibiting the activation of NF-κB in experimental ischemic stroke.