Lancemaside A inhibits microglial activation via modulation of JNK signaling pathway

Yeon Hui Jeong, Ji Sun Jung, Thi Kim Van Le, Dong Hyun Kim, Hee Sun Kim

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish
Pages (from-to)369-375
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume431
Issue number3
DOIs
StatePublished - 15 Feb 2013

Keywords

  • JNK signaling pathway
  • Lancemaside A
  • Microglia
  • Neuroinflammation
  • Neuroprotection

Fingerprint

Dive into the research topics of 'Lancemaside A inhibits microglial activation via modulation of JNK signaling pathway'. Together they form a unique fingerprint.

Cite this