LPS로 염증 유도된 RAW 264.7세포에 대한 참콩풍뎅이(Popillia flavosellata) 에탄올 추출물의 항염증 효과



Yoon, Young-Il;Hwang, Jae-Sam;Kim, Mi-Ae;Ahn, Mi Young;Lee, Young-Bo;Han, Myung Sae;Goo, Tae-Won;Yun, Eun-Young

  • 투고 : 2015.07.29
  • 심사 : 2015.08.11
  • 발행 : 2015.09.30


본 연구에서는 참콩풍뎅이(Popillia flavosellata) 에탄올 추출물(PFE)의 항염증 효능을 분석하기 위해 PFE를 농도별(500, 1,000, 2,000 μg/ml)로 대식세포인 RAW 264.7에 처리 시 최고 처리농도인 2,000 μg/ml까지 통계적인 유의성 있는 독성이 없음을 확인하였다. LPS (100 ng/ml)로 염증 유도된 RAW 264.7 세포에 PFE를 농도별(500, 1,000, 2,000 μg/ml)로 동시 처리 시 농도 의존적으로 염증성사이토카인인 TNF-α와 IL-6의 단백질 생성을 통계적인 유의성(p<0.001)있게 억제함을 확인하였다. 또한 염증 유도된 RAW 264.7 세포에 PFE 동시 처리 시 NF-κB p65의 핵으로 이동이 차단됨과 iNOS와 COX-2의 단백질 발현을 감소시키는 것을 확인하였다. 이상의 연구결과를 통해 참콩 풍뎅이는 염증에 의해 활성화된 TLR-4 신호전달과정을 조절하는 NF-κB p65의 활성과 염증성사이토카인 TNF-α와 IL-6의 생성 및 염증성효소 iNOS와 COX-2의 생성을 억제하는 항염증 효능이 있음을 확인하였다.


Anti-inflammation;lipopolysaccharide;Popillia flavosellata;pro-inflammatory cytokine;RAW 264.7 cells


  1. Vane, J. R. 1971. Inhibition of prostaglandin synthesis as a mechanism of action for the aspirin-like drugs. Nature 231, 232-235.
  2. Vlassara, H. 2005. Advanced glycation in health and disease role of the modern environment. Ann. N. Y. Acad. Sci. 1043, 452-460. https://doi.org/10.1196/annals.1333.051
  3. Wang, X., Luo, Y., Liao, W. B., Zhang, J. and Chen, T. M. 2013. Effect of osteoprotegerin in combination with interleukin-6 on inhibition of osteoclast differentiation. Chin. J. Traumatol. 16, 277-280.
  4. Yoo, J. M., Hwang, J. S., Goo, T. W. and Yun, E. Y. 2013. Comparative analysis of nutritional and harmful components in Korean and Chinese mealworms (Tenebrio molitor). J. Kor. Soc. Food Sci. Nutr. 42, 249-254. https://doi.org/10.3746/jkfn.2013.42.2.249
  5. Yoon, Y. I., Chung, M. Y., Hwang, J. S., Goo, T. W., Ahn, M. Y., Lee, Y. B., Han, M. S. and Yun, E. Y. 2014. Anti-inflammatory effect of Oxya chinensis sinuosa ethanol extract in LPS-induced RAW 264.7 cells. J. Life Sci. 24, 370-376. https://doi.org/10.5352/JLS.2014.24.4.370
  6. Rao, C. V., Indranie, C., Simi, B., Manning, P. T., Connor, J. R. and Reddy, B. S. 2002. Chemopreventive properties of a selective inducible nitric oxide synthase inhibitor in colon carcinogenesis, administered alone or in combination with celecoxib, a selective cyclooxygenase-2 inhibitor. Cancer Res. 62, 165-170.
  7. Medzhitov, R. 2008. Origin and physiological roles of inflammation. Nature 454, 428-435. https://doi.org/10.1038/nature07201
  8. Salvemini, D., Milko, T. P., Masferrer, J. L., Seibert, K., Currie, M. G. and Needleman, P. 1993. Nitric oxide activates cyclooxygenase enzymes. Proc. Nat. Acad. Sci. USA 90, 7240-7244. https://doi.org/10.1073/pnas.90.15.7240
  9. Shafran, Y., Zurgil, N., Afrimzon, E., Tauber, Y., Sobolev, M., Shainberg, A. and Deutsch, M. 2012. Correlative analyses of nitric oxide generation rates and nitric oxide synthase levels in individual cells using a modular cell-retaining device. Anal. Chem. 84, 7315-7322. https://doi.org/10.1021/ac202741z
  10. Tak, P. P. and Firestein, G. S. 2001. NF-kappaB: a key role in inflammatory diseases. J. Clin. Invest. 107, 7-11. https://doi.org/10.1172/JCI11830
  11. Tracey, D., Klareskog, L., Sasso, E. H., Salfeld, J. G. and Tak, P. P. 2008. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol. Ther. 117, 244-279. https://doi.org/10.1016/j.pharmthera.2007.10.001
  12. Swierkosz, T. A., Mitchell, J. A., Warner, T. D., Botting, R. M. and Vane, J. R. 1995. Co-induction of nitric oxide synthase and cyclo-oxygenase: interactions between nitric oxide and prostanoids. Br. J. Pharmacol. 114, 1335-1342. https://doi.org/10.1111/j.1476-5381.1995.tb13353.x
  13. Van Huis, A., Van ltterbeeck, J., Klunder, H., Mertens, E., Halloran. A., Muir, G. and Vantomme, P. 2013. Edible in sects:future prospects for food and feed security. Food and agriculture Organization of the United Nations, Rome, Italy.
  14. Miyataka, M., Rich, K. A., Ingram, M., Yamamoto, T. and Bing, R. J. 2002. Nitric oxide, anti-inflammatory drugs on renal prostaglandins and cyclooxygenase-2. Hypertension 39, 785-789. https://doi.org/10.1161/hy0302.105689
  15. Mitchell, J. A., Akarasereenont, P., Thiemermann, C., Flower, R. J. and Vane, J. R. 1993. Selectivity of nonsteroid anti-inflammatory drugs as inhibitors of constitutive and inducible cyclo-oxygenase. Proc. Nat. Acad. Sci. USA 90, 11693-11697. https://doi.org/10.1073/pnas.90.24.11693
  16. Monaco, C., Andreakos, E., Kiriakidis, S., Mauri, C., Bicknell, C., Foxwell, B., Cheshire, N., Paleolog, E. and Feldmann, M. 2004. Canonical pathway of nuclear factor kappa B activation selectively regulates proinflammatory and prothrombotic responses in human atherosclerosis. Proc. Nat. Acad. Sci. USA 101, 5634-5639. https://doi.org/10.1073/pnas.0401060101
  17. Nakanishi, M. and Rosenberg, D. W. 2013. Multifaceted roles of PGE2 in inflammation and cancer. Semin. Immunopathol. 35, 123-137. https://doi.org/10.1007/s00281-012-0342-8
  18. Paek, M. K., Hwang, J. M., Jung, K. S., Kim, T. W., Kim, M. C., Lee, Y. J., Cho, Y. B., Park, S. W., Lee, H. S., Ku, D. S., Jeong, J. C., Kim, K. G., Choi, D. S., Shin, E. H., Jwang, J. H., Lee, J. S., Kim, S. S. and Bea, Y. S. 2010. Checklist of Korean insects. Nature & Ecology, pp. 113.
  19. Park, J. Y., Heo, J. C., Woo, S. U., Yun, C. Y., Kang S. W., Hwang, J. S. and Lee, S. H. 2006. Anti-inflammatory and cellular protective effects on hydrogen peroxide-induced cytotoxicity of grasshopper extracts. Kor. J. Food Preserv. 13, 796-802.
  20. Rajendram, R., Saraswathy, S. and Rao, N. A. 2007. Photoreceptor mitochondrial oxidative stress in early experimental autoimmune uveoretinitis. Br. J. Ophthalmol. 91, 531-537. https://doi.org/10.1136/bjo.2006.101576
  21. Hink, U. and Münzel, T. 2006. COX-2, another important player in the nitric oxide-endothelin cross-talk: good news for COX-2 inhibitors? Circ. Res. 98, 1344-1346. https://doi.org/10.1161/01.RES.0000228471.38761.93
  22. Howes, L. G. 2007. Selective COX-2 inhibitors, NSAIDs and cardiovascular events - is celecoxib the safest choice? Ther. Clin. Risk Manag. 3, 831-845.
  23. Iwalewa, E. O., McGaw, L. J., Naidoo, V. and Eloff, J. N. 2007. Inflammation: the foundation of diseases and disorders. A review of phytomedicines of south african origin used to treat pain and inflammatory conditions. Afr. J. Biotechnol. 6, 2868-2885.
  24. Kang, C. H., Choi, Y. H., Choi, I. W., Lee, J. D. and Kim, G. Y. 2011. Inhibition of lipopolysaccharide-induced iNOS, COX-2, and TNF-α expression by aqueous extract of Orixa Japonica in RAW 264.7 cells via suppression of NF-κB activity. Trop. J. Pharm. Res. 10, 161-168.
  25. Kim, J. J., Jang, B. K., Lee, S. M., Choo, H. Y., Zhu, M. and Lee, D. W. 2011. Investigation of host plants and seasonal occurrence of Popillia flavosellata (Coleoptera: Rutelidae) ingolf courses. Asian J. Turfgrass Sci. 25, 22-29.
  26. Lee, S. Y., Kwon, H. K. and Lee, S. M. 2011. SHINBARO, a new herbal medicine with multifunctional mechanism for joint disease: first therapeutic application for the treatment of osteoarthritis. Arch. Pharm. Res. 34, 1773-1777. https://doi.org/10.1007/s12272-011-1121-0
  27. Gabay, C. 2006. Interleukin-6 and chronic inflammation. Arthritis Res. Ther. 8, S3.
  28. Giuliani, C., Napolitano, G., Bucci, I., Montani, V. and Monaco, F. 2001. NF-κB transcription factor: role in the pathogenesis of inflammatory, autoimmune, and neoplastic diseases and therapy implications. Clin. Ter. 152, 249-253.
  29. Ahmadi-Ashtiani, H. R., Rastegar, H. and Arkam, M. 2013. The inhibitory effect of silymarin on cell viability and cellular COX-2 and iNOS level in HepG2 cell line. Health Med. 7, 2008-2014.
  30. Arora, R. B., Kapoor, V., Basu, N. and Jain, A. P. 1971. Anti-inflammatory studies on Curcuma longa (turmeric). Indian J. Med. Res. 59, 1289-1295.
  31. Baldwin, A. S. Jr. 1996. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu. Rev. Immunol. 14, 649-683. https://doi.org/10.1146/annurev.immunol.14.1.649
  32. Brennan, F. M., Chantry, D., Jackson, A., Maini, R. and Feldmann, M. 1989. Inhibitory effect of TNF alpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet 2, 244-247.
  33. Cerella, C., Sobolewski, C., Dicato, M. and Diederich, M. 2010. Targeting COX-2 expression by natural compounds:a promising alternative strategy to synthetic COX-2 inhibitors for cancer chemoprevention and therapy. Biochem. Pharmachol. 15, 1801-1815.
  34. Chung, M. Y., Hwang, J. S., Goo, T. W. and Yun, E. Y. 2013. Analysis of general composition and harmful material of Protaetia brevitarsis. J. Life Sci. 23, 664-668. https://doi.org/10.5352/JLS.2013.23.5.664
  35. Ferrero-Miliani, L., Nielsen, O. H., Andersen, P. S. and Girardin, S. E. 2007. Chronic inflammation: Importance of NOD2 and NALP3 in interleukin-1beta generation. Clin. Exp. Immunol. 147, 227-235.