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 language | English |
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Pages (from-to) | 369-375 |
Number of pages | 7 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 431 |
Issue number | 3 |
DOIs | |
State | Published - 15 Feb 2013 |
Bibliographical note
Funding Information:This work was supported by the National Research Foundation (NRF) grant funded by the Korean government [Grant 2012-0009853 ].
Keywords
- JNK signaling pathway
- Lancemaside A
- Microglia
- Neuroinflammation
- Neuroprotection