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Obovatol attenuates microglia‐mediated neuroinflammation by modulating redox regulation
Author(s) -
Ock Jiyeon,
Han Hyung S,
Hong Su H,
Lee So Y,
Han YoungMin,
Kwon ByoungMog,
Suk Kyoungho
Publication year - 2010
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2010.00659.x
Subject(s) - neuroinflammation , microglia , proinflammatory cytokine , microbiology and biotechnology , nitric oxide , nitric oxide synthase , signal transduction , pharmacology , chemistry , reactive oxygen species , neurodegeneration , biology , biochemistry , inflammation , immunology , medicine , endocrinology , disease
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 IC 50 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.