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

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
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Inhibitory Effects of Euphorbia supina Rafin on the Production of Pro-Inflammatory Mediator by LPS-Stimulated RAW 264.7 Macrophages

LPS로 활성화된 RAW 264.7 대식세포에서 애기땅빈대(Euphorbia supina Rafin)의 염증매개물질 억제효과

  • Park, Sung-Chul (Dept. of Herbal Food Science, Daegu Haany University) ;
  • Son, Dae-Yeul (Dept. of Herbal Food Science, Daegu Haany University)
  • 박성철 (대구한의대학교 한방식품약리학과) ;
  • 손대열 (대구한의대학교 한방식품약리학과)
  • Received : 2010.12.21
  • Accepted : 2011.01.26
  • Published : 2011.04.30
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Abstract

This study was designed to evaluate the effect of hot water extract (ESW) and 70% ethanol extract (ESE) from Euphorbia supina Rafin on LPS-stimulated inflammatory response in RAW 264.7 macrophages. Upon investigation at concentrations up to $1000\;{\mu}g$/mL, ESW and ESE did not have any cytotoxic effects on RAW 264.7 macrophages. ESW induced inhibition of 21.6%~54.8% of nitric oxide (NO) production at 100~1000${\mu}g$/mL, and $PGE_2$ production was inhibited up to 25.7%~38.2% at 250~1000${\mu}g$/mL, proportional to the ESW concentrations. ESW induced inhibition of 66.1% and 54.3% of IL-6 production at 250 and $1000\;{\mu}g$/mL, respectively. ESE (100~1000${\mu}g$/mL) induced inhibition of 38.3%~77.5% of NO, 40%~94.7% of $PGE_2$, and 43.9%~89.4% of IL-6 production, proportional to the ESE concentrations. Only 44.1% of IL-10 production was inhibited at a concentration of $500\;{\mu}g$/mL. ESE induced an increase in TNF-${\alpha}$ production at a concentration of 100 and $250\;{\mu}g$/mL, whereas at high concentrations (500 and $1000\;{\mu}g$/mL), ESE induced inhibition of 19.2% and 92.4% of TNF-${\alpha}$ production, respectively. In conclusion, concentrations of more than $500\;{\mu}g$/mL ESE demonstrated effective immune-modulating activity through inhibition of NO, $PGE_2$, IL-6, IL-10, or TNF-${\alpha}$ production, as it relates to the macrophage's immuno-activity; therefore, ESE has potential as a good candidate substance for reduction of inflammatory responses.

본 연구는 애기땅빈대(Euphorbia supina Rafin.) 열수(ESW) 및 에탄올 추출물(ESE)의 항염증 효과를 조사하기 위하여 RAW 264.7 세포에서 LPS에 의해 생성되는 염증매개물질에 대한 억제효과를 조사하였다. ESW와 ESE은 조사된 모든 농도에서 95% 이상의 생존율을 보여 세포독성이 없는 것으로 확인되었다. ESW의 경우, NO의 생성을 100, 250, 500, $1000\;{\mu}g$/mL 농도에서 각각 21.6%, 31.9%, 44.3%, 54.8% 억제하였고, PGE2의 생성은 250, 500, $1000\;{\mu}g$/mL 농도에서 각각 25.7%, 34%, 38.2% 억제하여 농도 의존적이고 유의적인 억제효과가 확인되었다. IL-6의 생성은 250, $1000\;{\mu}g$/mL 농도에서 각각 66.1%, 54.3% 억제하였다. IL-10, TNF-${\alpha}$의 생성은 $500\;{\mu}g$/mL 농도에서 유의적인 증가를 나타냈다. ESE의 경우, NO의 생성을 100, 250, 500, $1000\;{\mu}g$/mL 농도에서 각각 38.3%, 66%, 74.7%, 77.5%, $PGE_2$의 생성은 100, 250, 500, $1000\;{\mu}g$/mL 농도에서 각각 40%, 51.8%, 92.4%, 94.7% 농도 의존적이고 유의적으로 억제하였다. IL-6의 생성은 100, 250, 500, $1000\;{\mu}g$/mL 농도에서 각각 43.9%, 48.9%, 69.7%, 89.4% 억제하였다. IL-10의 생성은 $500\;{\mu}g$/mL 농도에서 44.1% 억제하였고, TNF-${\alpha}$의 생성은 $1000\;{\mu}g$/mL 농도에서 92.4% 억제하였다. 결과를 종합해 볼때, 애기땅빈대는 ESW보다는 ESE의 경우가 LPS로 활성화된 RAW 264.7 대식세포에서의 염증매개물질 억제효과가 좋은 것으로 나타났으며, ESE는 저농도보다는 $500\;{\mu}g$/mL 이상의 고농도에서 NO, $PGE_2$, IL-6, IL-10, TNF-${\alpha}$와 같은 염증매개물질 억제효과가 좋은 것으로 확인되었다. 따라서 애기땅빈대 ESE는 $500\;{\mu}g$/mL 농도 이상에서 염증매개물질 억제 보조제로서 활용될 수 있을 것으로 사료된다.

Keywords

References

  1. Lee CB. 1989. Coloured flora of Korea. Hyangmunsa, Seoul, Korea. p 511.
  2. Choi JG. 2004. The medicine of grasses, flowers and trees. Hanmunhwa, Seoul, Korea. p 193-201.
  3. National China Medical Administration. 1999. China medical herbs. Shanghai science technology publisher, Shanghai, China. p 789-792.
  4. Lee SH, Tanaka T, Nonaka G, Nishioka I. 1991. Tannins and related compounds. CV. Monomeric and dimeric hydrolyzable tannins having a dehydrohexahydroxydiphenoyl group, supinanin, euphorscopin, euphorhelin and jolkianin, from Euphorbia species. Chem Pharm Bull 39: 630-638. https://doi.org/10.1248/cpb.39.630
  5. Agata I, Hatano T, Nakaya Y, Sugaya T, Nishibe S, Yoshida T, Okuda T. 1991. Tannins and related polyphenols of Euphorbiaceous plants. VIII. Eumaculin A and eusupinin A, and accompanying polyphenols from Euphorbia maculata L. and E. supina Rafin. Chem Pharm Bull 39: 881-883. https://doi.org/10.1248/cpb.39.881
  6. Fang Z, Zeng X, Zhang Y, Zhou G. 1993. Chemical constituents of spottedleaf euphorbia (Euphorbia supina). Zhongcayao 24: 230-233.
  7. An RB, Kwon JW, Kwon TO, Chung WT, Lee HS, Kim YC. 2007. Chemical constituents from the whole plants of Euphorbia supina Rafin. Kor J Pharmacogn 38: 291-295.
  8. Tanaka R, Matsunaga S. 1999. Terpenoids and steroids from several Euphorbiaceae and Pinaceae plants. Yakugaku Zasshi 119: 319-339. https://doi.org/10.1248/yakushi1947.119.5_319
  9. Chung BS, Kim HG. 1985. Studies on the terpenoid constituents of Euphorbia supina Rafin. Kor J Pharmacogn 16: 155-159.
  10. Tanaka R, Kurimoto M, Yoneda M, Matsunaga S. 1990. 17$\beta$,21$\beta$-Epoxyhopan-3$\beta$-ol and $\beta$-alnincanol from Euphorbia supina. Phytochemistry 29: 2253-2256. https://doi.org/10.1016/0031-9422(90)83047-5
  11. Hong HK, Kwak JH, Kang SC, Lee JW, Park JH, Ahn JW, Kang HS, Choung ES, Zee OP. 2008. Antioxidative constituents from whole plants of Euphorbia supina. Kor J Pharmacogn 39: 260-264.
  12. Cho W, Nam JW, Kang HJ, Windono T, Seo EK, Lee KT. 2009. Zedoarondiol isolated from the rhizoma of Curcuma heyneana is involved in the inhibition of iNOS, COX-2 and pro-inflammatory cytokines via the downregulation of NF-${\kappa}B$ pathway in LPS-stimulated murine macrophages. Int Immunopharmacol 9: 1049-1057. https://doi.org/10.1016/j.intimp.2009.04.012
  13. Yun HJ, Hoe SK. 2008. Anti-inflammatory effect of Injinhotang in RAW 264.7 cells. Kor J Herbol 23: 169-178.
  14. Choi WY, Jo MJ, Kim SC, Jung JY. 2009. Aucklandiae Radix has inhibiory effects of pro-inflammatory mediator in LPS-induced RAW 264.7 cell. Journal of Jeahan Oriental Medical Academy 7: 1-12.
  15. Lee YS, Kim HS, Kim SK, Kim SD. 2000. IL-6 mRNA expression in mouse peritoneal macrophages and NIH3T3 fibroblasts in response to Candida albicans. J Microbiol Biotechnol 10: 8-15
  16. Higuchi M, Higashi N, Taki H, Osawa T. 1990. Cytolytic mechanism of activated macrophages. Tumor necrosis fac tor and L-arginine-dependent mechanism act as synergistically as the major cytolytic mechanism of activated macrophages. J Immunol 144: 1425-1431.
  17. McDaniel ML, Kwon G, Hill JR, Marshall CA, Corbett JA. 1996. Cytokines and nitric oxides in islet inflammation and diabetes. Proc Soc Exp Biol Med 211: 24-32. https://doi.org/10.3181/00379727-211-43950D
  18. Kim DH, Park SJ, Jung JY, Kim SC, Byun SH. 2009. Antiinflammatory effects of the aqueous extract of Hwangnyenhaedok- tang in LPS-activated macrophage cells. Kor J Herbol 24: 39-47.
  19. Willeaume V, Kruys V, Mijatovic T, Huez G. 1996. Tumor necrosis factor-alpha production induced by viruses and by lipopolysaccharides in macrophages: similarities and differences. J Inflamm 46: 1-12
  20. McCartney-Francis N, Allen JB, Mizel DE, Albina JE, Xie QW, Nathan CF, Wahl SM. 1993. Suppression of arthritis by an inhibitor of nitric oxide synthase. J Exp Med 178: 749-754. https://doi.org/10.1084/jem.178.2.749
  21. Choi YJ, Jo WS, Kim HJ, Nam BH, Kang EY, Oh SJ, Lee GA, Jeong MH. 2010. Anti-inflammatory effect of Chlorella ellipsoidea extracted from seawater by organic solvents. Kor J Fish Aquat Sci 43: 39-45. https://doi.org/10.5657/kfas.2010.43.1.039
  22. Desai A, Vyas T, Amiji M. 2008. Cytotoxicity and apoptosis enhancement in brain tumor cells upon coadministration of paclitaxel and ceramide in nanoemulsion formulations. J Pharm Sci 97: 2745-2756. https://doi.org/10.1002/jps.21182
  23. Kim PJ, Yun HJ, Heo SK, Kim KA, Kim DW, Kim JE, Park SD. 2009. Anti-inflammatory effect of Bodusan. Kor J Herbol 24: 49-56.
  24. Jeoung YJ, Choi SY, An CS, Jeon YH, Park DK, Lim BO. 2009. Comparative effect on anti-inflammatory activity of the Phellinus linteus and Phellinus linteus grown in germinated brown rice extracts in murine macrophage RAW 264.7 cells. Kor J Medicinal Crop Sci 17: 97-101
  25. Lowenstein CJ, Snyder SH. 1992. Nitric oxide, a novel biologic messenger. Cell 70: 705-707. https://doi.org/10.1016/0092-8674(92)90301-R
  26. Sunyer T, Rothe L, Jiang X, Anderson F, Osdoby P, Collin- Osdoby P. 1997. $Ca^{2+}$ or phorbol ester but not inflammatory stimuli elevate inducible nitric oxide synthase messenger ribonucleic acid and nitric oxide (NO) release in avian osteoclasts: autocrine NO mediates $Ca^{2+}$-inhibited bone resorption. Endocrinology 138: 2148-2162. https://doi.org/10.1210/en.138.5.2148
  27. Weisz A, Cicatiello I, Esumi H. 1996. Regulation of the mouse inducible-type nitric oxide synthase gene promoter by interferon-gamma, bacterial lipopolysaccharide and NG-monomethyl-L-arginene. Biochem J 316: 209-215 https://doi.org/10.1042/bj3160209
  28. Kim PJ, Yun HJ, Heo SK, Kim KA, Kim DW, Kim JE, Park SD. 2009. Anti-inflammatory effect of Bodusan. Kor J Herbol 24: 49-56.
  29. Rocca B, FitzGerald GA. 2002. Cyclooxygenases and prostaglandins: shaping up the immune response. Int Immunopharmacol 2: 603-630. https://doi.org/10.1016/S1567-5769(01)00204-1
  30. Park JY, Pillinger MH, Abramson SB. 2006. Prostagladin $E_2$ synthesis and secretion: the role of $PGE_2$ synthases. Clin Immunol 119: 229-240. https://doi.org/10.1016/j.clim.2006.01.016
  31. Bhattacharyya A, Pathak S, Datta S, Chattopadhyay S, Basu J, Kundu M. 2002. Mitogen-activated protein kinases and NF-kappaB regulate H. pylori-mediated IL-8 release from macrophages. Biochem J 366: 376-382.
  32. Binetruy B, Smeal T, Kariu M. 1991. Ha-Ras augments c-Jun activity and stimulates phosphoylation of its activation domain. Nature 351: 122-127. https://doi.org/10.1038/351122a0
  33. Kindt TJ, Goldsby RA, Osborne. 2008. Kuby immunology. 6th ed. The Korean Society for Microbiology, E Public, Seoul, Korea. p 600-623.
  34. Yoon KR, Kim YJ, Lee E, Lee JM. 2009. Anti-inflammatory effect of Coptidis Rhizoma. Kor J Herbol 24: 79-86.

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