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Int Immunopharmacol. 2018 Apr;57:72-81. doi: 10.1016/j.intimp.2018.02.014. Epub 2018 Feb 22.

XQ-1H protects against ischemic stroke by regulating microglia polarization through PPARγ pathway in mice.

Author information

1
State Key Laboratory of Natural Medicines, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
2
State Key Laboratory of Natural Medicines, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: yunmanli@cpu.edu.cn.
3
State Key Laboratory of Natural Medicines, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: weirongfang@cpu.edu.com.

Abstract

Cerebral ischemic and reperfusion injury often accompany with inflammation, and lead to severe neuronal damage, which further result in neurological disorders and memory disorders. In this study, we researched XQ-1H, a novel derivative of ginkgolide B, protecting against ischemic stroke in mice through regulation of microglia polarization. Middle cerebral artery occlusion (MCAO)/reperfusion in mice is applied to mimic ischemic stroke in vivo. Immediately after MCAO, mice are intragastric administrated with different dose (31 or 62 mg/kg) of XQ-1H for one or continuative three days. The in vivo experiments indicated that post-treatment with XQ-1H decreased cerebral infarction size, lessened brain edema, improved behavior and memory recover, inhibited pro-inflammatory and promoted anti-inflammatory cytokines expression and releasing in MCAO mice. Oxygen-glucose deprivation/reoxygenation (OGD/R) injury in BV-2 (microglia) cells is served in vitro. The in vitro findings revealed that incubation with XQ-1H protected against BV2 from OGD/R injury, regulated BV2 polarized from pro-inflammatory into anti-inflammatory phenotype, and promoted PPARγ mobilizing from nuclear to cytoplasm. In conclusion, the present study demonstrates that XQ-1H alleviated ischemic stroke by regulating balance of pro-/anti-inflammatory microglia polarization through PPARγ pathway both in vivo and in vitro, offering an alternative medication for stroke associated with inflammation.

KEYWORDS:

Inflammation; Ischemic stroke; Microglia; PPARγ; XQ-1H

PMID:
29475098
DOI:
10.1016/j.intimp.2018.02.014
[Indexed for MEDLINE]

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