Journal of Nutrition and Health

  • 제51권4호
  • /
  • Pages.323-329
  • /
  • 2018
  • /
  • 2288-3886(pISSN)
  • /
  • 2288-3959(eISSN)
한국영양학회 (The Korean Nutrition Society)
권호 표지
DOI QR코드

DOI QR Code

RAW 264.7 세포에서 왕지네 추출물의 항염 활성

Anti-inflammatory activities of Scolopendra subspinipes mutilans in RAW 264.7 cells

  • 투고 : 2018.07.24
  • 심사 : 2018.08.01
  • 발행 : 2018.08.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

만성 염증은 현대사회에서 다양한 질병을 유발하는 주요 원인으로 작용하기 때문에 항염증 활성을 가진 소재의 연구는 염증 관련 질병의 예방과 치료에 있어서 중요하다. 본 연구에서는 LPS에 의해 염증을 유도한 RAW 264.7 세포에서 제주왕지네 (Scolopendra subspinipes mutilans) 에탄올 추출물의 염증 조절 기전을 확인하여 항염증 소재로서의 가능성을 조사하였다. LPS에 의해 증가된 NO 생성과 iNOS 발현은 왕지네 추출물에 의해 감소되었고 pro-inflammatory cytokine으로 알려진 $IL-1{\beta}$, IL-6의 발현에서도 유사한 결과를 보였다. 왕지네 추출물은 LPS에 의해 유도된 $NF-{\kappa}B$의 핵으로의 전이와 $I{\kappa}B$의 분해를 동시에 억제하였고 $NF-{\kappa}B$ inhibitor의 처리는 NO 생성과 iNOS 발현을 더욱 억제하였다. 이상의 결과는 왕지네 추출물이 $NF-{\kappa}B$ 활성 조절을 통해 염증 반응의 지표로 사용되는 NO 생성 및 pro-inflammatory cytokine의 발현을 효과적으로 억제하여 항염 활성을 가진 소재로서의 가능성을 보여주는 것으로 염증에 의해 유발되는 다양한 질병을 효율적으로 제어하는 소재를 개발하는데 있어서 주요한 정보를 제공할 것으로 생각된다.

Purpose: The dried body of Scolopendra subspinipes mutilans has long been used as a traditional Korean medicinal food, but little is known about its mechanisms of action. In this study, we investigated the anti-inflammatory activities of Scolopendra subspinipes mutilans and possible mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Methods: Cytotoxicity of Scolopendra subspinipes mutilans extract (SSME) was measured by MTT assay, anti-inflammatory activities were analyzed by nitric oxide (NO) production, the expression of inducible NO synthase (iNOS) and the mRNA level of pro-inflammatory cytokines such as $interleukin-1{\beta}$ ($IL-1{\beta}$) and interleukin-6 (IL-6). Nuclear translocation of nuclear factor-kappa B ($NF-{\kappa}B$) p65 subunit and degradation of inhibitory kappa B ($I{\kappa}B$) were examined by western blot. Results: SSME inhibited LPS-induced NO production and iNOS expression without cytotoxicity. Up-regulation of LPS-induced pro-inflammatory cytokines, $IL-1{\beta}$ and IL-6 was dose dependently attenuated by SSME. Exposure of pyrrolidine dithiocarbamate, an $NF-{\kappa}B$ specific inhibitor, accelerated the inhibitory effects of SSME on NO production and iNOS expression in LPS-stimulated cells. Moreover, translocation of $NF-{\kappa}B$ from the cytosol to the nucleus and degradation of $I{\kappa}B$ were decreased by treatment with SSME in LPS-induced cells. Conclusion: These results suggest that the SSME might have the inhibitory effects on inflammation, partly through inhibition of the $NF-{\kappa}B$ signaling pathway.

키워드

참고문헌

  1. Ferrero-Miliani L, Nielsen OH, Andersen PS, Girardin SE. Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1$\beta$ generation. Clin Exp Immunol 2007; 147(2): 227-235. https://doi.org/10.1111/j.1365-2249.2006.03261.x
  2. Saha S, Shalova IN, Biswas SK. Metabolic regulation of macrophage phenotype and function. Immunol Rev 2017; 280(1): 102-111. https://doi.org/10.1111/imr.12603
  3. Aktan F. iNOS-mediated nitric oxide production and its regulation. Life Sci 2004; 75(6): 639-653. https://doi.org/10.1016/j.lfs.2003.10.042
  4. Gabay C. Interleukin-6 and chronic inflammation. Arthritis Res Ther 2006; 8 Suppl 2: S3.
  5. Meng XM, Tang PM, Li J, Lan HY. Macrophage phenotype in kidney injury and repair. Kidney Dis (Basel) 2015; 1(2): 138-146. https://doi.org/10.1159/000431214
  6. Alexander C, Rietschel ET. Bacterial lipopolysaccharides and innate immunity. J Endotoxin Res 2001; 7(3): 167-202. https://doi.org/10.1179/096805101101532675
  7. Limtrakul P, Yodkeeree S, Pitchakarn P, Punfa W. Antiinflammatoryeffects of proanthocyanidin-rich red rice extractvia suppression of MAPK, AP-1 and NF-$kappa$B pathways in Raw264.7 macrophages. Nutr Res Pract 2016; 10(3): 251-258. https://doi.org/10.4162/nrp.2016.10.3.251
  8. Doyle SL, O'Neill LA. Toll-like receptors: from the discovery of NF$kappa$B to new insights into transcriptional regulations in innate immunity. Biochem Pharmacol 2006; 72(9): 1102-1113. https://doi.org/10.1016/j.bcp.2006.07.010
  9. Pemberton RW. Insects and other arthropods used as drugs in Korean traditional medicine. J Ethnopharmacol 1999; 65(3): 207-216. https://doi.org/10.1016/S0378-8741(98)00209-8
  10. Kim SC, Seo GY, Lee SW, Park SJ, Kim JH, Ahn SH, Hwang SY. Biological activities of Scolopendrid Pharmacopuncture. J Pharmacopuncture 2010; 13(3): 5-13. https://doi.org/10.3831/KPI.2010.13.3.005
  11. Ding D, Guo YR, Wu RL, Qi WY, Xu HM. Two new isoquinoline alkaloids from Scolopendra subspinipes mutilans induce cell cycle arrest and apoptosis in human glioma cancer U87 cells. Fitoterapia 2016; 110: 103-109. https://doi.org/10.1016/j.fitote.2016.03.004
  12. Ma W, Liu R, Qi J, Zhang Y. Extracts of centipede Scolopendra subspinipes mutilans induce cell cycle arrest and apoptosis in A375 human melanoma cells. Oncol Lett 2014; 8(1): 414-420. https://doi.org/10.3892/ol.2014.2139
  13. Lee W, Hwang JS, Lee DG. A novel antimicrobial peptide, scolopendin, from Scolopendra subspinipes mutilans and its microbicidal mechanism. Biochimie 2015; 118: 176-184. https://doi.org/10.1016/j.biochi.2015.08.015
  14. Lee JH, Kim IW, Kim MA, Ahn MY, Yun EY, Hwang JS. Antimicrobial activity of the scolopendrasin V peptide identified from the centipede Scolopendra subspinipes mutilans. J Microbiol Biotechnol 2017; 27(1): 43-48. https://doi.org/10.4014/jmb.1609.09057
  15. Kim IW, Lee JH, Kwon YN, Kim SH, Yun EY, Nam SH, Ahn MY, Hwang JS. Inhibitory effect of melanin synthesis using organic solvent extracts from Scolopendra subspinipes mutilans. J Seric Entomol Sci 2014; 52(1): 1-5. https://doi.org/10.7852/jses.2014.52.1.1
  16. Hakim MA, Yang S, Lai R. Centipede venoms and their components: resources for potential therapeutic applications. Toxins (Basel) 2015; 7(11): 4832-4851. https://doi.org/10.3390/toxins7114832
  17. Blum-Degen D, Muller T, Kuhn W, Gerlach M, Przuntek H, Riederer P. Interleukin-1$\beta$ and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer's and de novo Parkinson's disease patients. Neurosci Lett 1995; 202(1-2): 17-20. https://doi.org/10.1016/0304-3940(95)12192-7
  18. Jiang Z, Li C, Arrick DM, Yang S, Baluna AE, Sun H. Role of nitric oxide synthases in early blood-brain barrier disruption following transient focal cerebral ischemia. PLoS One 2014; 9(3): e93134. https://doi.org/10.1371/journal.pone.0093134
  19. Sharma JN, Al-Omran A, Parvathy SS. Role of nitric oxide in inflammatory diseases. Inflammopharmacology 2007; 15(6): 252-259. https://doi.org/10.1007/s10787-007-0013-x
  20. Li M, Dai FR, Du XP, Yang QD, Chen Y. Neuroprotection by silencing iNOS expression in a 6-OHDA model of Parkinson's disease. J Mol Neurosci 2012; 48(1): 225-233. https://doi.org/10.1007/s12031-012-9814-5
  21. Yoon YI, Hwang JS, Kim MA, Ahn MY, Lee YB, Han MS, Goo TW, Yun EY. Inhibition of inflammation by Popillia flavosellata ethanol extract in LPS-induced RAW264.7 macrophages. J Life Sci 2015; 25(9): 993-999. https://doi.org/10.5352/JLS.2015.25.9.993
  22. Kim HJ, Kim DH, Lee JY, Hwang JS, Lee JH, Lee SG, Jeong HG, An BJ. Study of anti-inflammatory effect of CopA3 peptide derived from Copris tripartitus. J Life Sci 2013; 23(1): 38-43. https://doi.org/10.5352/JLS.2013.23.1.38
  23. Kim DH, Kim HJ, Lee JY, Hwang JS, Kim IW, Lee SG, Jeong HG, An BJ. Anti-inflammatory effect of HaGF peptide of Harmonia axyridis. J Life Sci 2013; 23(4): 495-500. https://doi.org/10.5352/JLS.2013.23.4.495
  24. Yoon YI, Chung MY, Hwang JS, Goo TW, Ahn MY, Lee YB, Han MS, Yun EY. Anti-inflammatory effect of Oxya chinensis sinuosa ethanol extract in LPS-induced RAW 264.7 cells. J Life Sci 2014; 24(4): 370-376. https://doi.org/10.5352/JLS.2014.24.4.370
  25. Kim JE, Kim SG, Kang SJ, Kim CS, Choi YS. Effect of antioxidation and antibacterial activity on crude extract and characterization of american cockroaches (Periplaneta americana L.) in Korea. J Seric Entomol Sci 2015; 53(2): 135-142. https://doi.org/10.7852/JSES.2015.53.2.135
  26. Park YJ, Kim HS, Lee HY, Hwang JS, Bae YS. A novel antimicrobial peptide isolated from centipede Scolopendra subspinipes mutilans stimulates neutrophil activity through formyl peptide receptor 2. Biochem Biophys Res Commun 2017; 494(1-2): 352-357. https://doi.org/10.1016/j.bbrc.2017.10.019
  27. Yoon CH, Kim DC, Ko WM, Kim KS, Lee DS, Kim DS, Cho HK, Seo J, Kim, SY, Oh H, Kim YC. Anti-neuroinflammatory effects of quercetin-3-O-glucuronide isolated from the leaf of Vitis labruscana on LPS-induced neuroinflammation in BV2 cells. Korean J Pharmacogn 2014; 45(1): 17-22.
  28. Park E, Chun HS. Green tea polyphenol epigallocatechine gallate (EGCG) prevented LPS-induced BV-2 microglial cell activation. J Life Sci 2016; 26(6): 640-645. https://doi.org/10.5352/JLS.2016.26.6.640
  29. Beinke S, Ley SC. Functions of NF-$\kappa$B1 and NF-$\kappa$B2 in immune cell biology. Biochem J 2004; 382(Pt 2): 393-409. https://doi.org/10.1042/BJ20040544
  30. Li X, Stark GR. NF$\kappa$B-dependent signaling pathways. Exp Hematol 2002; 30(4): 285-296. https://doi.org/10.1016/S0301-472X(02)00777-4

피인용 문헌

  1. 두충을 포함하는 한방추출물(Mix)의 항노화, 항염, 미백 효능 활성에 관한 연구 vol.45, pp.1, 2019, https://doi.org/10.15230/scsk.2019.45.1.37
  2. Toxic Animal-Based Medicinal Materials Can Be Effective in Treating Endometriosis: A Scoping Review vol.13, pp.2, 2021, https://doi.org/10.3390/toxins13020145
  3. Edible arachnids and myriapods worldwide - updated list, nutritional profile and food hygiene implications vol.7, pp.3, 2018, https://doi.org/10.3920/jiff2020.0046
  4. A Correlation Study on In Vitro Physiological Activities of Soybean Cultivars, 19 Individual Isoflavone Derivatives, and Genetic Characteristics vol.10, pp.12, 2021, https://doi.org/10.3390/antiox10122027