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Lancemaside A inhibits microglial activation via modulation of JNK signaling pathway

Title
Lancemaside A inhibits microglial activation via modulation of JNK signaling pathway
Authors
Jeong Y.-H.Jung J.-S.Le T.K.V.Kim D.-H.Kim H.-S.
Ewha Authors
김희선
SCOPUS Author ID
김희선scopus
Issue Date
2013
Journal Title
Biochemical and Biophysical Research Communications
ISSN
0006-291XJCR Link
Citation
vol. 431, no. 3, pp. 369 - 375
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Microglial activation plays an important role in neurodegenerative diseases. Thus, controlling microglial activation is considered to be a promising therapeutic target for neurodegenerative diseases. In the present study, we found that lancemaside A, a triterpenoid saponin isolated from Codonopsis lanceolata, inhibited iNOS and proinflammatory cytokines in LPS-stimulated BV2 microglial cells. By analyzing molecular mechanisms underlying the anti-inflammatory effects of lancemaside A, we found that lancemaside A selectively inhibited LPS-induced JNK phosphorylation among the three types of MAP kinases. A JNK-specific inhibitor, SP600125, like lancemaside A, significantly inhibited not only NO, TNF-α, and IL-6 productions, but also NF-κB and AP-1 activities, suggesting that JNK inhibition is largely involved in the anti-inflammatory mechanism of lancemaside A. Interestingly, both the lancemaside A and SP600125 inhibited ROS production by suppressing the expression and/or phosphorylation of NADPH oxidase subunit proteins, such as p47phox, p67phox, and gp91phox. The antioxidant effects of lancemaside A and SP600125 appear to be related with an increase of hemeoxygenase-1 expression by both agents. Finally, we demonstrated the neuroprotective effects of lancemaside A and SP600125 in microglia-neuron coculture systems. Collectively, our data suggest that JNK pathway plays a key role mediating anti-inflammatory effects of lancemaside A in LPS-stimulated microglia. © 2013 Elsevier Inc.
DOI
10.1016/j.bbrc.2013.01.049
Appears in Collections:
의과대학 > 의학과 > Journal papers
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