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Anti-inflammatory Mechanism of Ginseng Saponin Metabolite Rh3 in Lipopolysaccharide-Stimulated Microglia: Critical Role of 5′-Adenosine Monophosphate-Activated Protein Kinase Signaling Pathway

Title
Anti-inflammatory Mechanism of Ginseng Saponin Metabolite Rh3 in Lipopolysaccharide-Stimulated Microglia: Critical Role of 5′-Adenosine Monophosphate-Activated Protein Kinase Signaling Pathway
Authors
Lee Y.Y.Park J.-S.Lee E.-J.Lee S.-Y.Kim D.-H.Kang J.L.Kim H.-S.
Ewha Authors
이지희김희선박진선이은정
SCOPUS Author ID
이지희scopus; 김희선scopus; 박진선scopus; 이은정scopus
Issue Date
2015
Journal Title
Journal of Agricultural and Food Chemistry
ISSN
0021-8561JCR Link
Citation
vol. 63, no. 13, pp. 3472 - 3480
Keywords
AMPKGinsenoside Rh3MicrogliaNeuroinflammationSignaling molecules
Publisher
American Chemical Society
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Ginsenoside Rh3 is a bacterial metabolite of Rg5, which is the main constituent of heat-processed ginseng. The present study was undertaken to examine the anti-inflammatory effect of ginsenoside Rh3 in lipopolysaccharide (LPS)-stimulated microglia. Rh3 inhibits the expressions of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6, at mRNA and protein levels, while Rh3 enhanced anti-inflammatory hemeoxygenase-1 expression. Moreover, Rh3 inhibited nuclear factor-κB (NF-κB) by upregulation of sirtuin 1 (SIRT1) and enhanced Nrf2 DNA-binding activities. Analysis of signaling pathways revealed that Rh3 enhanced the phosphorylation of 5′-adenosine monophosphate-activated protein kinase (AMPK) and inhibited Akt and janus kinase 1 (JAK1)/signal transducer and activator of transcription 1 (STAT1) induced by LPS. By treatment of BV2 cells with AICAR (a pharmacological activator of AMPK), we found that AMPK is an upstream regulator of phosphatidylinositol 3-kinase (PI3K)/Akt and JAK1/STAT1. Furthermore, AMPK knockdown experiments demonstrated the anti-inflammatory role of AMPK in LPS/Rh3-treated BV2 microglia. Our data collectively suggest that Rh3 exerts an anti-inflammatory effect in microglia by modulating AMPK and its downstream signaling pathways. © 2015 American Chemical Society.
DOI
10.1021/jf506110y
Appears in Collections:
의과대학 > 의학과 > Journal papers
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