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KMID : 0352720080320040315
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Journal of Ginseng Research
2008 Volume.32 No. 4 p.315 ~ p.323
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Compound K Rich Fractions Regulate NF-xB-dependent Inflammatory Responses and Protect Mice from Endotoxin-induced Lethal Shock
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Yang Chul-Su
Do Jae-Ho
Wee Jae-Joon
Kim Young-Sook
Yuk Jae-Min
Ko Sung-Ryong
Sohn Hyun-Joo
Jo Eun-Kyeong
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Abstract
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In the previous studies, we isolated the compound K rich fractions (CKRF) and showed that CKRF inhibited Toll-like receptor (TLR) 4- or TLR9-induced inflammatory signaling. To extend our previous studies,1) we investigated the molecular mechanisms of CKRF in the TLR4-associated signaling via nuclear factor (NF)-xB, and in vivo role of CKRF for induction of tolerance in lipopolysaccharide (LPS)-induced septic shock. In murine bone marrow-dervied macrophages, CKRF significantly inhibited the induction of mRNA expression of proinflammatory mediators such as tumor necrosis factor-α, interleukin-6, cyclooxygenase-2, and inducible nitric oxide synthase. In addition, CKRF significantly attenuated the transcriptional activities of TLR4/LPS-induced NF-xB. Nuclear translocation of NF-xB in response to LPS stimulation was significantly abrogated by pre-treatment with CKRF. Furthermore, CKRF inhibited the recruitment of p65 to the interferon-sensitive response element flanking region in response to LPS. Finally, oral administration of CKRF significantly protected mice from Gram-negative bacterial LPS-induced lethal shock and inhibited systemic inflammatory cytokine levels. Together, these results demonstrate that CKRF modulates the TLR4-dependent NF- xB activation, and suggest a therapeutic role for Gram-negative septic shock.
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KEYWORD
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Compound K rich fractions, Toll-like receptor 4, nuclear factor xB, endotoxemia
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