Journal of the Korean Society of Food Science and Nutrition (한국식품영양과학회지)

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
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Anti-Inflammatory Effect of Hot Water Extract of Aronia Fruits in LPS-Stimulated RAW 264.7 Macrophages

LPS 자극 RAW 264.7 대식세포에 있어서 아로니아 열매 열수 추출물의 항염증 효과

  • Yang, Hui (Department of Microbiology, College of Medicine, Konyang University) ;
  • Oh, Kwang-Hoon (Department of Physical Education, College of Education, Kongju National University) ;
  • Yoo, Yung Choon (Department of Microbiology, College of Medicine, Konyang University)
  • 양혜 (건양대학교 의과대학 미생물학교실) ;
  • 오광훈 (공주대학교 사범대학 체육교육과) ;
  • 유영춘 (건양대학교 의과대학 미생물학교실)
  • Received : 2014.09.16
  • Accepted : 2014.11.20
  • Published : 2015.01.31
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Abstract

In this study, anti-inflammatory activity of hot water extract of Aronia fruits (AF-H) was examined. Pre-treatment with AF-H significantly inhibited production of nitric oxide (NO) and prostaglandin E-2 in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The inhibitory effect of AF-H on LPS-induced inflammation was also confirmed by down-regulation of inducible NO synthase as well as cyclooxygenase-2 protein expression. Furthermore, treatment with AF-H significantly inhibited secretion of inflammatory cytokines such as tumor-necrosis $factor-{\alpha}$ and interleukin-6. Signal transduction pathway studies further indicated that AF-H inhibited LPS-induced activation of nuclear $factor-{\kappa}B$, but not mitogen-activated protein kinase. Treatment with AF-H also partially protected against LPS-induced lethal shock in C57BL/6 mice, although its effect was not statistically significant. These results suggest that AF-H is a more promising nutraceutical or medicinal agent for inhibition of LPS-induced inflammation or inflammation-related diseases.

본 연구에서는 아로니아 열매 추출물(AF-H)의 항염증 활성을 조사하기 위하여 LPS 자극에 의해 유도된 RAW 264.7 macrophage의 염증반응에서 AF-H의 염증매개인자 및 염증성 사이토카인 분비 억제활성과 이에 관련된 세포 내 작용기전 해석을 수행하였다. LPS($1{\mu}g/mL$)로 RAW 264.7 세포를 24시간 자극하는 염증모델에서 세포독성을 나타내지 않는 안전한 농도의 AF-H($0{\sim}500{\mu}g/mL$)를 LPS 처리 12시간 전에 처리하여 NO 및 PGE2의 분비 억제활성을 측정하였다. 그 결과 AF-H 처리에 의해 NO와 PGE2의 생성이 처리 농도에 의존하여 유의하게 억제되었으며, 이들 염증매개인자의 생합성 효소인 iNOS 및 COX-2의 세포 내 발현도 현저하게 억제되는 것으로 관찰되었다. 또한 AF-H의 처리에 의해 염증성 사이토카인인 $TNF-{\alpha}$와 IL-6의 분비도 유의하게 억제되는 것으로 확인하였다. 이러한 AF-H에 의한 항염증 활성의 세포 내 기전을 해석하기 위하여 LPS 자극에 의해 유도되는 MAPK와 $NF-{\kappa}B$ 전사인자의 활성화에 대한 억제 효과를 조사하였다. 그 결과 AF-H는 MAPK의 인산화에는 별다른 영향을 미치지 않고 $NF-{\kappa}B$의 활성화($I{\kappa}B$ 인산화)를 효과적으로 억제하는 것으로 확인되었다. 한편 LPS에 의한 in vivo 패혈증 모델에서 AF-H에 의한 패혈증 억제활성을 측정한 결과 비록 통계학적으로 유의하지는 않으나 AF-H 투여에 의해 생존율과 50% 사망률의 연장 효과가 관찰되었다. 이들 결과를 종합해 보면 아로니아 열매 열수추출물은 $NF-{\kappa}B$의 활성화 억제를 통해 NO, PGE2, $TNF-{\alpha}$ 및 IL-6 등의 염증매개인자와 사이토카인의 생성을 억제하는 항염증 활성을 지니는 것으로 확인되었다.

Keywords

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