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

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
권호 표지
DOI QR코드

DOI QR Code

Anti-inflammatory Effects of Ethanol Extract from Bark of Acer barbinerve Maxim

청시닥나무 수피 에탄올 추출물의 항염증 효과

  • Lee, Han-Na (Dept. of Food Science and Nutrition, Hallym University) ;
  • Kim, Jin-Kyu (Natural Products Research Institute, Gyeonggi Institute of Science & Technology Promotion) ;
  • Kwon, Gyoo-Taik (Dept. of Food Science and Nutrition, Hallym University) ;
  • Shim, Jae-Hoon (Dept. of Food Science and Nutrition, Hallym University) ;
  • Kim, Jong-Dai (Dept. of Food Science and Biotechnology, College of Agriculture and Life Science, Kangwon National University) ;
  • YoonPark, Jung-Han (Dept. of Food Science and Nutrition, Hallym University)
  • 이한나 (한림대학교 식품영양학과) ;
  • 김진규 (경기과학기술진흥원 천연물신약 연구소) ;
  • 권규택 (한림대학교 식품영양학과) ;
  • 심재훈 (한림대학교 식품영양학과) ;
  • 김종대 (강원대학교 농업생명과학대학 식품생명공학과) ;
  • 윤정한 (한림대학교 식품영양학과)
  • Received : 2012.05.21
  • Accepted : 2012.07.12
  • Published : 2012.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Acer barbinerve Maxim belongs to the Aceraceae tree family and is often consumed as an Oriental medicine. In this study, we investigated whether or not ethanol extract from the bark of A. barbinerve Max. (EBA) inhibits lipopolysaccharide (LPS)-induced inflammatory responses in Raw264.7 macrophages. EBA was fractionated using n-hexane, $CH_2Cl_2$, ethyl acetate (EtOAc), and water. Raw264.7 cells were treated with 20 ${\mu}g/mL$ of EBA and the EBA fractions. EBA inhibited LPS-induced nitric oxide (NO) production. Among the three fractions, EtOAc fraction of EBA (EFEBA) was the most effective in inhibiting LPS-induced NO production without significant cytotoxicity in Raw264.7 cells. EFEBA futher reduced LPS-induced expression of inducible NO synthase (iNOS) proteins and its corresponding mRNA. Additionally, EFEBA decreased the mRNA levels of interleukin (IL)-6, IL-$1{\beta}$, and tumor necrosis factor-${\alpha}$ in LPS-treated Raw264.7 cells. Lastly, EFEBA inhibited LPS-induced degradation of the inhibitor of kappaBalpha ($I{\kappa}B{\alpha}$) as well as phosphorylation of p65 nuclear factor-${\kappa}B$ (NF-${\kappa}B$). These results indicate that EFEBA exhibits strong anti-inflammatory effects and can be developed as a potential anti-inflammatory agent.

본 연구를 통하여 청시닥나무의 에탄올 추출물은 쥐 대식세포인 Raw264.7 세포에 LPS로 유도된 염증반응에 미치는 효과가 있음을 확인하였다. 청시닥나무 목질부와 수피부에 에탄올을 가하여 추출한 뒤 그 추출물과 분획물의 NO 생성능 및 세포증식능을 실험한 결과 수피부의 EtOAc 분획이 세포증식능에 영향을 주지 않으면서 NO의 생성을 억제함을 확인하였다. 청시닥나무 수피부 에탄올 추출물 EtOAc 분획(EFEBA)은 Raw264.7 세포에서 LPS에 의해 생성된 NO의 분비와 iNOS의 단백질 및 mRNA의 발현을 농도 의존적으로 감소시켰고, 염증 반응 시 생성되는 IL-6, IL-$1{\beta}$ 그리고 TNF-${\alpha}$의 mRNA의 발현도 현저히 감소시켰다. 또한 $I{\kappa}B{\alpha}$의 degradation을 감소시키고 p65의 인산화를 감소시켜 NF-${\kappa}B$ signaling을 통해 염증작용을 조절함을 확인하였다.

Keywords

References

  1. Sadaki O. 1996. The development of functional and materials. Bioindustry 13: 44-50.
  2. Cadenas E, Davies KJ. 2000. Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 29: 222-230. https://doi.org/10.1016/S0891-5849(00)00317-8
  3. Cai Y, Luo Q, Sun M, Corke H. 2004. Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer. Life Sci 74: 2157-2184. https://doi.org/10.1016/j.lfs.2003.09.047
  4. Giles GI, Tasker KM, Jacob C. 2001. Hypothesis: The role of reactive sulfur species in oxidative stress. Free Radical Bio Med 31: 1279-1283. https://doi.org/10.1016/S0891-5849(01)00710-9
  5. Sohal RS, Weindruch R. 1996. Oxidative stress, caloric restriction, and aging. Science 273: 59-63. https://doi.org/10.1126/science.273.5271.59
  6. Fubini B, Hubbard A. 2003. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation by silica in inflammation and fibrosis. Free Radic Biol Med 34: 1507-1516. https://doi.org/10.1016/S0891-5849(03)00149-7
  7. Zedler S, Faist E. 2006. The impact of endogenous triggers on trauma-associated inflammation. Curr Opin Crit Care 12: 595-601. https://doi.org/10.1097/MCC.0b013e3280106806
  8. Mariathasan S, Monack DM. 2007. Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation. Nat Rev Immunol 7: 31-40. https://doi.org/10.1038/nri1997
  9. Zamora R, Vodovotz Y, Billiar TR. 2000. Inducible nitric oxide synthase and inflammatory diseases. Mol Med 6: 347-373.
  10. Hofseth LJ, Ying L. 2006. Identifying and defusing weapons of mass inflammation in carcinogenesis. Biochim Biophys Acta 1765: 74-84.
  11. Tamir S, Tannenbaum SR. 1996. The role of nitric oxide (NO) in the carcinogenic process. Biochim Biophys Acta 1288: F31-F36.
  12. Nathan C. 1992. Nitric oxide as a secretory product of mammalian cells. FASEB J 6: 3051-3064.
  13. Moncada S, Palmer RM, Higgs EA. 1991. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43: 109-142.
  14. Nathan C, Xie QW. 1994. Nitric oxide synthases: roles, tolls, and controls. Cell 78: 915-918. https://doi.org/10.1016/0092-8674(94)90266-6
  15. Ghosh S, Hayden MS. 2008. New regulators of NF-${\kappa}B$ in inflammation. Nat Rev Immunol 8: 837-848. https://doi.org/10.1038/nri2423
  16. Majdalawieh A, Ro HS. 2010. Regulation of $I{\kappa}B{\alpha}$ function and NF-${\kappa}B$ signaling: AEBP1 is a novel proinflammatory mediator in macrophages. Mediators Inflamm 2010: 823821.
  17. Kim TW. 2010. The Woody Plants of Korea. Kyo-Hak Publishing Co., Ltd, Seoul, Korea. p 465.
  18. Kwon DJ, Bae YS. 2009. Phenolic compounds from the bark of Acer Barbinerve Max. Mokcheae Konghak 37: 164-170.
  19. Lee HY, Jeong HS. 2005. Isolation and identification of antimicrobial substance from Canavalia gladiata. Food Sci Biotechnol 14: 268-274.
  20. Donà M, Dell'Aica I, Calabrese F, Benelli R, Morini M, Albini A, Garbisa S. 2003. Neutrophil restraint by green tea: inhibition of inflammation, associated angiogenesis, and pulmonary fibrosis. J Immunol 170: 4335-4341. https://doi.org/10.4049/jimmunol.170.8.4335
  21. Gorzalczany S, López P, Acevedo C, Ferraro G. 2011. Anti-inflammatory effect of Lithrea molleoides extracts and isolated compounds. J Ethnophamacol 133: 994-998. https://doi.org/10.1016/j.jep.2010.11.031
  22. Nakamura ES, Kurosaki F, Arisawa M, Mukainaka T, Takayasu J, Okuda M, Tokuda H, Nishino H, Pastore F. 2002. Cancer chemopreventive effects of a Brazilian folk medicine, Juca, on in vivo two-stage skin carcinogenesis. J Ethnophamacol 81: 135-137. https://doi.org/10.1016/S0378-8741(02)00047-8
  23. Lizarraga D, Touriño S, Reyes-Zurita FJ, de Kok TM, van Delft JH, Maas LM, Briede JJ, Centelles JJ, Torres JL, Cascante M. 2008. Witch hazel (Hamamelis virginiana) fractions and the importance of gallate moieties-electron transfer capacities in their antitumoral properties. J Agric Food Chem 56: 11675-11682. https://doi.org/10.1021/jf802345x
  24. Denizot F, Lang R. 1986. Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods 89: 271-277. https://doi.org/10.1016/0022-1759(86)90368-6
  25. Cho HJ, Kim WK, Kim EJ, Jung KC, Park S, Lee HS, Tyner AL, Park JH. 2003. Conjugated linoleic acid inhibits cell proliferation and ErbB3 signaling in HT-29 human colon cell line. Am J Physiol Gastrointest Liver Physiol 284: G996-G1005.
  26. Cho HJ, Seon MR, Lee YM, Kim J, Kim JK, Kim SG, Park JH. 2008. 3,3'-Diindolylmethane suppresses the inflammatory response to lipopolysaccharide in murine macrophages. J Nutr 138: 17-23.
  27. Laml PD, Mandal PK, Hak SY, Hwang SG. 2010. Study of the molecular mechanism of anti-inflammatory activity of Bee venom in lipopolysaccharide stimulated RAW 264.7 macrophages. Trop J Pharm Res 9: 19-26.
  28. Shin NR, Lee DY, Shin SJ, Kim KS, Yoo HS. 2004. Regulation of proinflammatory mediator production in RAW264.7 macrophage by Vibrio vulnificus luxS and smcR. FEMS Immunol Med Microbiol 41: 169-176. https://doi.org/10.1016/j.femsim.2004.03.001
  29. Laflamme N, Rivest S. 2001. Toll-like receptor 4: the missing link of the cerebral innate immune response triggered by circulating gram-negative bacterial cell wall components. FASEB J 15: 155-163. https://doi.org/10.1096/fj.00-0339com
  30. MacMicking J, Xie QW, Nathan C. 1997. Nitric oxide and macrophage function. Annu Rev Immunol 15: 323-350. https://doi.org/10.1146/annurev.immunol.15.1.323
  31. Iezzi A, Ferri C, Mezzetti A, Cipollone F. 2007. COX-2: friend or foe? Curr Pharm Des 13: 1715-1721. https://doi.org/10.2174/138161207780831293
  32. Kavya R, Saluja R, Singh S, Dikshit M. 2006. Nitric oxide synthase regulation and diversity: implications in Parkinson's disease. Nitric Oxide 15: 280-294. https://doi.org/10.1016/j.niox.2006.07.003
  33. Weigert A, Brüne B. 2008. Nitric oxide, apoptosis and macrophage polarization during tumor progression. Nitric Oxide 19: 95-102. https://doi.org/10.1016/j.niox.2008.04.021
  34. Delgado AV, McManus AT, Chambers JP. 2003. Production of tumor necrosis factor-alpha, interleukin 1-beta, interleukin 2, and interleukin 6 by rat leukocyte subpopulations after exposure to substance P. Neuropeptides 37: 355-361. https://doi.org/10.1016/j.npep.2003.09.005
  35. Hawiger J. 2001. Innate immunity and inflammation: a transcriptional paradigm. Immunol Res 23: 99-109. https://doi.org/10.1385/IR:23:2-3:099
  36. Nam NH. 2006. Naturally occurring NF-${\kappa}B$ inhibitors. Mini Rev Med Chem 6: 945-951. https://doi.org/10.2174/138955706777934937
  37. Schwabe RF, Sakurai H. 2005. $IKK{\beta}$ phosphorylates p65 at S468 in transactivaton domain 2. FASEB J 19: 1758-1760.
  38. Chae HS, Kang OH, Choi JG, Oh YC, Lee YS, Brice OO, Chong MS, Lee KN, Shin DW, Kwon DY. 2010. Methyl gallate inhibits the production of interleukin-6 and nitric oxide via down-regulation of extracellular-signal regulated protein kinase in RAW 264.7 cells. Am J Chin Med 38: 973-983. https://doi.org/10.1142/S0192415X10008391

Cited by

  1. Anti-Inflammatory Effects of Extracts from Caesalpinia sappan L. on Skin Inflammation vol.42, pp.3, 2013, https://doi.org/10.3746/jkfn.2013.42.3.384
  2. Anti-inflammatory Effect of Ethanol Extract from Sargassum fulvellum on Lipopolysaccharide Induced Inflammatory Responses in RAW 264.7 Cells and Mice Ears vol.43, pp.8, 2014, https://doi.org/10.3746/jkfn.2014.43.8.1158
  3. Anti-inflammatory Activity of Solvent Fractions from Ginseng Berry Extract in LPS-Induced RAW264.7 Cells vol.22, pp.6, 2014, https://doi.org/10.7783/KJMCS.2014.22.6.449
  4. Anti-Inflammatory Effect of Ethanol Extract from Grateloupia elliptica Holmes on Lipopolysaccharide-Induced Inflammatory Responses in RAW 264.7 Cells and Mice Ears vol.44, pp.8, 2015, https://doi.org/10.3746/jkfn.2015.44.8.1128
  5. Anti-inflammatory Activity of Sargassum micracanthum Water Extract vol.57, pp.3, 2014, https://doi.org/10.3839/jabc.2014.036
  6. Anti-inflammatory Activity of the Undaria pinnatifida Water Extract vol.55, pp.4, 2012, https://doi.org/10.3839/jabc.2012.035
  7. Effect of type II collagen extract on immunosuppression induced by methotrexate in rats vol.14, pp.5, 2018, https://doi.org/10.12965/jer.1836480.240