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Title 

Obovatol attenuates microglia-mediated neuroinflammation by modulating redox regulation

 

오보바톨에 의한 신경 염증 조절 기전규명

Authors 

J OckH S HanS H HongS Y LeeYoung Min HanByoung-Mog KwonK Suk

Publisher 

Wiley-Blackwell

Issue Date 

2010

Citation 

British Journal of Pharmacology, vol. 159, no. 8, pp. 1646-1662

Keywords 

Chemical geneticsMicrogliaNeuroinflammationNeuroprotectionObovatolPeroxiredoxin 2

Abstract 

Background and purpose: Obovatol isolated from the medicinal herb Magnolia obovata exhibits a variety of biological activities. Here, the effect of obovatol and its mechanism of action on microglial activation, neuroinflammation and neurodegeneration were investigated. Experimental approach: In microglial BV-2 cells stimulated with lipopolysaccharide (LPS), we measured nitric oxide (NO) and cytokine production, and activation of intracellular signalling pathways by reverse transcription-polymerase chain reaction and Western blots. Cell death was assayed in co-cultures of activated microglia (with bacterial LPS) and neurons and in LPS-induced neuroinflammation in mice in vivo. Key results: Obovatol inhibited microglial NO production with an IC50 value of 10 μM. Obovatol also inhibited microglial expression of proinflammatory cytokines and inducible nitric-oxide synthase, which was accompanied by the inhibition of multiple signalling pathways such as nuclear factor kappa B, signal transducers and activators of transcription 1, and mitogen-activated protein kinases. In addition, obovatol protected cultured neurons from microglial toxicity and inhibited neuroinflammation in mice in vivo. One molecular target of obovatol in microglia was peroxiredoxin 2 (Prx2), identified by affinity chromatography and mass spectrometry. Obovatol enhanced the reactive oxygen species (ROS)-scavenging activity of Prx2 in vitro, thereby suppressing proinflammatory signalling pathways of microglia where ROS plays an important role. Conclusions and implications: Obovatol is not only a useful chemical tool that can be used to investigate microglial signalling, but also a promising drug candidate against neuroinflammatory diseases. Furthermore, our results indicate that Prx2 is a novel drug target that can be exploited for the therapeutic modulation of neuroinflammatory signalling.

ISSN 

0007-1188

Link 

http://dx.doi.org/10.1111/j.1476-5381.2010.00659.x

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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