Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Compound K (CK) Rich Fractions from Korean Red Ginseng Inhibit Toll-like Receptor (TLR) 4- or TLR9-mediated Mitogen-activated Protein Kinases Activation and Pro-inflammatory Responses in Murine Macrophages

고려홍삼으로부터 분리한 compound K 함유분획에 의한 대식세포의 toll-like receptor-의존성 신호전달로 활성조절 분석

  • Yang, Chul-Su (Department of Microbiology, College of Medicine, Chungnam National University) ;
  • Ko, Sung-Ryong (Ginseng Research Group, KT&G Central Research Institute) ;
  • Cho, Byung-Goo (Ginseng Research Group, KT&G Central Research Institute) ;
  • Lee, Ji-Yeon (Department of Microbiology, College of Medicine, Chungnam National University) ;
  • Kim, Ki-Hye (Department of Microbiology, College of Medicine, Chungnam National University) ;
  • Shin, Dong-Min (Department of Microbiology, College of Medicine, Chungnam National University) ;
  • Yuk, Jae-Min (Department of Microbiology, College of Medicine, Chungnam National University) ;
  • Sohn, Hyun-Joo (Ginseng Research Group, KT&G Central Research Institute) ;
  • Kim, Young-Sook (Ginseng Research Group, KT&G Central Research Institute) ;
  • Wee, Jae-Joon (Ginseng Research Group, KT&G Central Research Institute) ;
  • Do, Jae-Ho (Ginseng Research Group, KT&G Central Research Institute) ;
  • Jo, Eun-Kyeong (Department of Microbiology, College of Medicine, Chungnam National University)
  • 양철수 (충남대학교 의과대학 미생물학교실) ;
  • 고성룡 (KT&G 중앙연구소) ;
  • 조병구 (KT&G 중앙연구소) ;
  • 이지연 (충남대학교 의과대학 미생물학교실) ;
  • 김기혜 (충남대학교 의과대학 미생물학교실) ;
  • 신동민 (충남대학교 의과대학 미생물학교실) ;
  • 육재민 (충남대학교 의과대학 미생물학교실) ;
  • 손현수 (KT&G 중앙연구소) ;
  • 김영숙 (KT&G 중앙연구소) ;
  • 위재준 (KT&G 중앙연구소) ;
  • 도재호 (KT&G 중앙연구소) ;
  • 조은경 (충남대학교 의과대학 미생물학교실)
  • Published : 2007.12.31
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Abstract

Compound K (CK), a protopanaxadiol ginsenoside metabolite, was previously shown to have immunomodulatory effects. In this study, we isolated the CK rich fractions (CKRF) from Korean Red Ginseng and investigated the regulation of CKRF-mediated inflammatory signaling during Toll-like receptor (TLR)-mediated cellular activation. Among various TLR ligands, CKRF considerably abrogated TLR4- or TLR9-induced inflammatory signaling. Both LPS and CpG-containing oligodeoxynucleotides (CpG-ODN) stimulation rapidly activates mitogen-activated protein kinases [MAPKs; extracellular signal-regulated kinases 1/2 and p38], NF-${\kappa}B$, and expression of pro-inflammatory cytokines tumor necrosis factor-${\alpha}$, and interleukin-6 in murine bone marrow-derived macrophages (BMDMs) in a time- and dose-dependent manner. Of interest, pre-treatment of CKRF in either LPS/TLR4- or CpG-ODN/TLR9-stimulated macrophages substantially attenuated the LPS-induced inflammatory cytokine production and mRNA expressions, as well as MAPK and NF-${\kappa}B$ activation. To our knowledge, this is the first description of the inhibitory roles for CKRF in TLR4- or TLR9-associated signaling in BMDMs. Collectively, these results demonstrate that CKRF specifically modulates distinct TLR4 and TLR9-mediated inflammatory responses, and further studies are urgently needed for their in vivo roles for potential therapeutic uses, such as in systemic inflammatory syndromes.

본 연구에서는 고려홍삼으로부터 새로 분리한 CK 함유분획을 이용하여 마우스 대식세포에 대한 선천면역반응 조절에 미치는 영향을 조사하였다. 본 연구에서 사용된 농도의 CK 함유분획에서는 세포독성 효과가 관찰되지 않았으며 CK함유 분획의 전처리에 의하여 그람음성세균의 LPS, 또는 CpG-ODN에 의해 유도되는 NF-${\kappa}B$와 MAPK 활성 및 전염증성 사이토카인, NO의 분비가 TLR4 및 TLR9 특이적으로 억제되었다. 이와 같은 결과는 CK 함유분획이 TLR4을 매개로하는 염증반응뿐만 아니라 TLR9을 통한 염증반응에도 영향을 미치는 것으로 해석된다. 따라서 앞으로 CK 함유 분획에 포함된 개별 사포닌 등 시료 성분에 대한 면밀한 분석, 그리고 이들 개별 물질이 각각의 신호전달 체계에 미치는 영향과 그 기작에 대한 연구가 더욱 필요할 것으로 사료되며 염증억제제로서의 개발 가능성을 탐구하기 위한 생체 내에서의 효능 및 작용기전 분석이 요구된다.

Keywords

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