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Non-saponin fraction of red ginseng inhibits monocyte-to-macrophage differentiation and inflammatory responses in vitro

홍삼 비사포닌 분획의 단핵세포 분화와 염증반응에 대한 억제효과

  • Kang, Bobin (Department of Integrated Biomedical and Life Science, Graduate School, Korea University) ;
  • Kim, Chae Young (Department of Integrated Biomedical and Life Science, Graduate School, Korea University) ;
  • Hwang, Jisu (Department of Integrated Biomedical and Life Science, Graduate School, Korea University) ;
  • Choi, Hyeon-Son (Department of Food Science and Technology, College of Natural Science, Seoul Women's University)
  • 강보빈 (고려대학교 보건과학대 의생명융합과학과) ;
  • 김채영 (고려대학교 보건과학대 의생명융합과학과) ;
  • 황지수 (고려대학교 보건과학대 의생명융합과학과) ;
  • 최현선 (서울여자대학교 식품공학과)
  • Received : 2018.11.11
  • Accepted : 2018.12.27
  • Published : 2019.02.28

Abstract

The aim of this study was to investigate the effects of red ginseng-derived non-saponin fraction (NSF) on inflammatory responses and monocyte-to-macrophage differentiation in RAW264.7 and THP-1. NSF effectively inhibited inflammatory responses by downregulating nitric oxide (NO) production and protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). NSF ($2000{\mu}g/mL$) decreased the levels of NO, iNOS, and COX-2 by 33, 83, and 64%, respectively. NSF inhibited the differentiation of monocyte-to-macrophage by decreasing cell adherence along with downregulation of the cluster of differentiation molecule $11{\beta}$ ($CD11{\beta}$) and CD36. In addition, pro-inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin 6, and monocyte chemoattractant protein 1 (MCP-1), were significantly reduced with NSF treatment. The NSF-mediated inhibition of inflammatory responses was due to the regulation of nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). NSF effectively suppressed the translocation of $NF-{\kappa}B$ into the nucleus, while nuclear Nrf2 and its target protein, heme oxygenase-1, levels were significantly increased.

본 연구에서는 홍삼 비사포닌 분획(NSF)의 항 염증 효과를 마우스 대식세포와 인간유래 단핵세포에서 확인하였다. NSF는 마우스 대식세포에서 LPS로 유도된 NO, iNOS 그리고 COX-2의 양 뿐만 아니라 IL-6, $TNF-{\alpha}$, MCP-1과 같은 염증성 싸이토카인의 생성량을 유의적으로 감소시켰다. 인간 유래 단핵세포에서는 PMA에 의해 유도되는 대식세포로의 분화를 효과적으로 억제하면서 분화인자인 $CD11{\beta}$와 CD36의 발현을 유의적으로 감소시켰다. 마우스 대식세포에서와 마찬가지로 염증성 싸이토카인들의 생성량 또한 감소하였는데, 이러한 NSF의 항 염증 효과는 두 전사인자의 조절작용에 의한 것으로 사료된다. 즉 NSF는 $NF-{\kappa}B$의 핵으로 이동을 감소시킴으로써 전사활성을 억제하여 염증성 싸이토카인들의 발현을 저해하고 이와 반대로 Nrf2의 발현과 핵으로의 이동을 증가시켜 항산화 효소이면서 항 염증 작용을 나타내는 HO-1의 발현을 촉진하는 것으로 관찰되었다. 따라서 NSF는 $NF-{\kappa}B$와 Nrf2의 두 가지 신호전달체계를 조절함으로써 항 염증 작용을 나타냈으며 이를 홍삼 NSF의 항 염증 기작으로 보고하는 바이다.

Keywords

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Fig. 1. Effect of NSF on viability of RAW264.7 and THP-1 cells.

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Fig. 2. Effect of NSF on inflammatory responses in RAW264.7 cells.

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Fig. 3. Effect of NSF on monocyte-to-macrophage differentiation and differentiation factors in THP-1 cells.

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Fig. 4. Effect of NSF on inflammatory cytokines in RAW264.7 (A) and THP-1 (B) cells.

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Fig. 5. Effect of NSF on NF-κB translocation into nucleus in RAW264.7 cells.

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Fig. 6. Effect of NSF on the protein expression level of Nrf2, Keap1, and HO-1, and Nrf2 nuclear translocation in RAW264.7 cells.

Table 1. Total polyphenol contents (TPC), total flavonoid contents (TFC) and radical scavenging activities of NSF

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