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Anti-inflammatory mechanism of ginsenoside Rh1 in lipopolysaccharide- stimulated microglia: Critical role of the protein kinase A pathway and hemeoxygenase-1 expression
- Anti-inflammatory mechanism of ginsenoside Rh1 in lipopolysaccharide- stimulated microglia: Critical role of the protein kinase A pathway and hemeoxygenase-1 expression
- Jung J.-S.; Shin J.A.; Park E.-M.; Lee J.-E.; Kang Y.-S.; Min S.-W.; Kim D.-H.; Hyun J.-W.; Shin C.-Y.; Kim H.-S.
- Ewha Authors
- 김희선; 박은미
- SCOPUS Author ID
- 김희선; 박은미
- Issue Date
- Journal Title
- Journal of Neurochemistry
- vol. 115, no. 6, pp. 1668 - 1680
- SCI; SCIE; SCOPUS
- Microglia activation plays a pivotal role in neurodegenerative diseases, and thus controlling microglial activation has been suggested as a promising therapeutic strategy for neurodegenerative diseases. In the present study, we showed that ginsenoside Rh1 inhibited inducible nitric oxide synthase, cyclooxygenase-2, and pro-inflammatory cytokine expression in lipopolysaccharide (LPS)-stimulated microglia, while Rh1 increased anti-inflammatory IL-10 and hemeoxygenase-1 (HO-1) expression. Suppression of microglial activation by Rh1 was also observed in the mouse brain following treatment with LPS. Subsequent mechanistic studies revealed that Rh1 inhibited LPS-induced MAPK phosphorylation and nuclear factor-κB (NF-κB)-mediated transcription without affecting NF-κB DNA binding. As the increase of pCREB (cAMP responsive element-binding protein) is known to result in suppression of NF-κB-mediated transcription, we examined whether Rh1 increased pCREB levels. As expected, Rh1 increased pCREB, which was shown to be related to the anti-inflammatory effect of Rh1 because pre-treatment with protein kinase A inhibitors attenuated the Rh1-mediated inhibition of nitric oxide production and the up-regulation of IL-10 and HO-1. Furthermore, treatment of HO-1 shRNA attenuated Rh1-mediated inhibition of nitric oxide and reactive oxygen species production. Through this study, we have demonstrated that protein kinase A and its downstream effector, HO-1, play a critical role in the anti-inflammatory mechanism of Rh1 by modulating pro- and anti-inflammatory molecules in activated microglia. © 2010 The Authors. Journal of Neurochemistry © 2010 International Society for Neurochemistry.
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