Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Anti-Inflammmatiry Effects of Nerium indicum Ethanol Extracts through Suppression of NF-kappaB Activation

NF-κB 활성 저해를 통한 협죽도 에탄올 추출물의 항염증 효능

  • Kim, Tae-Hwan (Departments of Internal Oriental Medicine Dongeui University College of Oriental Medicine) ;
  • Ko, Seog-Soon (Gaya Middle School) ;
  • Park, Cheol (Blue-Bio Industry Regional Innovation Center, Dong-Eui University) ;
  • Park, Sang-Eun (Departments of Internal Oriental Medicine Dongeui University College of Oriental Medicine) ;
  • Hong, Sang-Hoon (Departments of Internal Oriental Medicine Dongeui University College of Oriental Medicine) ;
  • Kim, Byung-Woo (Department of Biomaterial Control, Graduate School, Dong-Eui University) ;
  • Choi, Yung-Hyun (Biochemistry, and Research Institute of Oriental Medicine, Dongeui University College of Oriental Medicine)
  • 김태환 (동의대학교 한의과대학 내과학교실) ;
  • 고석순 (가야여자중학교) ;
  • 박철 (블루바이오소재 개발센터) ;
  • 박상은 (동의대학교 한의과대학 내과학교실) ;
  • 홍상훈 (동의대학교 한의과대학 내과학교실) ;
  • 김병우 (동의대학교 대학원 바이오물질제어학과) ;
  • 최영현 (동의대학교 한의과대학 생화학교실 및 한의학연구소)
  • Received : 2010.05.30
  • Accepted : 2010.07.19
  • Published : 2010.08.30
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Abstract

Nerium indicum, an India-Pakistan-originated shrub belonging to the oleander family, is reported to possess many pharmacological activities including cardiac muscle stimulation, and anti-diabetes, anti-angiogenesis, anti-cancer and neuro-protective activities. However, the anti-inflammatory properties of N. indicum were unclear. In this study, we investigated the effects of ethanol extract of the N. indicum leaf and stem (ENIL and ENIS) on the expression of anti-inflammatory mediators in U937 human pre-monocytic cell models. In U937 cells stimulated with phorbol 12-myristate-13-acetate (PMA), pre-treatment with ENIS significantly inhibited the expression of both cyclooxygenase-2 (COX-2) mRNA and protein, which are associated with inhibition of the release of prostaglandin $E_2\;(PGE_2)$, whereas the inhibitory effects appeared weakly in ENIL. Moreover, ENIS significantly attenuated PMA-induced IkappaB ($I{\kappa}B$) degradation and suppressed elevated nuclear factor kappa B (NF-${\kappa}B$) nuclear translocation. Taken together, these findings provide important new insights that N. indicum exhibits anti-inflammatory properties by suppressing the transcription of pro-inflammatory cytokine genes through the NF-kB signaling pathway.

정상세포뿐 만 아니라 형질 전환된 세포의 증식조절에 중요한 역할을 하는 것으로 알려진 COX-2는 전사조절인자인 NF-${\kappa}B$에 의해서 조절되며, 염증반응에 있어서 중요한 역할을 하는 PGE2의 생성에 관여하는 것으로 알려져 있다. 본 연구에서는 U937 인체혈구세포에서 염증유발인자인 PMA에 의해서 유발되는 염증반응에 있어서 중요한 역할을 하는 COX-2 및 COX-2의 산물인 PGE2와 COX-2의 발현에 영향을 미치는 전사조절인자인 NF-${\kappa}B$의 발현에 협죽도 잎 및 줄기의 에탄올 추출물인 ENIL 및 ENIS가 어떠한 영향을 미치는 지를 조사하였다. PMA가 처리된 U937 세포에서 COX-1의 발현에는 아무런 영향을 미치지 못하였지만 COX-2의 발현 증가가 유도되었고 이에 따른 PGE2의 생성이 증가되었다. PMA에 의해서 증가된 COX-2의 발현이 ENIS 선처리에 의하여 거의 완벽하게 억제되었고 그에 따른 PGE2의 생성도 현저하게 감소되었다. ENIS에 의한 COX-2의 발현 및 PGE2의 생성억제가 전사조절인자인 NF-${\kappa}B$와 상관성이 있는지를 조사한 결과, 핵 내로의 NF-${\kappa}B$ 이동이 ENIS 선처리에 의하여 억제되는 것으로 나타났다. 이는 ENIS가 NF-${\kappa}B$의 활성 억제를 통하여 COX-2의 발현 및 PGE2의 생성을 효과적으로 억제함으로서 항염증 효능을 가진다는 것을 의미하는 결과이다. 하지만 ENIL의 경우에는 이상에서와 같은 이러한 변화들이 매우 약하게 나타나는 것으로 조사되어 ENIS와 비교해서 항염증 효능이 낮은 것으로 나타났다. 본 연구 결과는 협죽도의 항염증기전에 대한 생화학적 해석 및 이를 활용한 향후 지속적인 연구를 위한 귀중한 자료가 될 것으로 생각된다.

Keywords

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