Journal of Applied Biological Chemistry

  • Volume 66
  • /
  • Pages.46-52
  • /
  • 2023
  • /
  • 1976-0442(pISSN)
  • /
  • 2234-7941(eISSN)
The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
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Anti-inflammatory effect of naringenin-7-O-phosphate in LPS-induced RAW 264.7 cells

LPS로 유도된 RAW 264. 7 대식세포에서 Naringenin-7-O-phosphate의 항염증 활성

  • Hyehyun Hong (Department of Pharmaceutical Engineering & Biotechnology, Sunmoon University) ;
  • Tae-Jin Park (Department of Pharmaceutical Engineering & Biotechnology, Sunmoon University) ;
  • Byeong Min Choi (Department of Pharmaceutical Engineering & Biotechnology, Sunmoon University) ;
  • Yu-Jung Yi (Department of Pharmaceutical Engineering & Biotechnology, Sunmoon University) ;
  • Seung-Young Kim (Department of Pharmaceutical Engineering & Biotechnology, Sunmoon University)
  • Received : 2023.01.03
  • Accepted : 2023.01.19
  • Published : 2023.12.31
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Abstract

The most abundant flavanone of grapefruits, naringenin (NN), is well known for its hepatoprotective, anti-lipid peroxidation and anti-carcinogenic effects. We generated three derivatives from NN using this technique in previous studies. Among them, it was confirmed that naringenin-7-O-phosphate (N7P), whose biological and physicochemical properties were not reported, showed a water solubility 45 times higher than that of NN. Therefore, in this study, the anti-inflammatory activity was evaluated in RAW 264.7 cells to investigate the potential physiological activity of N7P. As a result, N7P showed nitric oxide (NO) inhibitory activity at concentrations that did not show toxicity. In addition, prostaglandin E2 (PGE2) showed significant inhibitory activity from the lowest concentration of 12.5 μM and showed increased inhibitory activity compared to NN. In addition, as a result of western blot, N7P showed increased cyclooxygenase-2 (COX-2) inhibitory activity than NN, and effectively inhibited NO and PGE2 by significantly inhibiting their expression pathways. N7P also inhibited inflammatory cytokines, including tumor necrosis factor-α, interleukin-6. Based on these results, we propose that N7P can be used as a potent antiinflammatory agent.

플라보노이드는 광범위한 생물학적 활성을 가진 중요한 식물 2차 대사 산물로, 본 연구에서 사용된 naringenin (NN)은 자몽에 가장 풍부한 플라바논의 하나로 간 보호, 항지질 과산화 및 항암 활성에 관한 연구가 보고되었다. 우리는 이전 연구에서 biorenovation 기법을 NN에 적용하여 naringenin-7-O-Glucoside(prunin), naringenin-7-O-phosphate (N7P), 6''-O-Succinyl prunin과 같은 3가지 유도체를 합성하였으며 그 중 생물학적 및 물리화학적 특성이 보고되지 않은 N7P가 NN보다 45배 증가한 수용해도를 나타냄을 확인하였다. 따라서 본 연구에서는 N7P의 추가적인 생리활성 조사하고자 RAW 264.7 세포에서 항염증 활성을 평가하였으며 N7P는 세포 독성이 나타나지 않는 농도에서 유효한 inducible NO synthase (iNOS), cyclooxygenase-2(COX-2) 억제 활성을 보였으며 이들의 발현 경로를 유의하게 억제함으로써 nitric oxide (NO) 및 prostaglandin E2 (PGE2)를 효과적으로 억제하였다. 뿐만 아니라 pro-inflammatory cytokines인 tumor necrosis factor-α (TNF-α)와 interleukin-6 (IL-6)의 발현 또한 유의하게 억제하는 것으로 확인되었다. 이러한 결과를 근거로 N7P가 다양한 염증 인자를 표적으로 하는 항염증 소재로 적용될 수 있음을 제안한다.

Keywords

Acknowledgement

본 논문은 중소벤처기업부와 한국산업기술진흥원의 지역특화산업육성 +R&D 사업의 지원을 받아 수행된 연구결과입니다 (S3090174).

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