Anti-inflammatory mechanism of ginsenoside Rh1 in lipopolysaccharide-stimulated microglia: critical role of the protein kinase A pathway and hemeoxygenase-1 expression
- Authors
- Jung, Ji-Sun; Shin, Jin A.; Park, Eun-Mi; Lee, Jung-Eun; Kang, Young-Sook; Min, Sung-Won; Kim, Dong-Hyun; Hyun, Jin-Won; Shin, Chan-Young; Kim, Hee-Sun
- Issue Date
- Dec-2010
- Publisher
- WILEY
- Keywords
- CREB; ginsenoside Rh1; HO-1; neuroinflammation; PKA
- Citation
- JOURNAL OF NEUROCHEMISTRY, v.115, no.6, pp 1668 - 1680
- Pages
- 13
- Journal Title
- JOURNAL OF NEUROCHEMISTRY
- Volume
- 115
- Number
- 6
- Start Page
- 1668
- End Page
- 1680
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/13085
- DOI
- 10.1111/j.1471-4159.2010.07075.x
- ISSN
- 0022-3042
1471-4159
- Abstract
- P>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-kappa B (NF-kappa B)-mediated transcription without affecting NF-kappa B DNA binding. As the increase of pCREB (cAMP responsive element-binding protein) is known to result in suppression of NF-kappa B-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.
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