DOI QR코드

DOI QR Code

흰쥐에서 염산-에탄올로 유발된 위염에 대한 HEAC 추출물과 그 주성분의 억제효과

Protective Effects of HEAC and its Primary Active Compound on HCl-ethanol Induced Gastritis in Rats

  • 최원식 (순천향대학교 생명공학과) ;
  • 장도연 (동방 FTL 합성연구소) ;
  • 이경락 (순천향대학교 생명공학과) ;
  • 김승한 (순천향대학교 생명공학과)
  • Choi, Won-Sik (Department of Biotechnology, Soonchunhyang University) ;
  • Jang, Do-Yoen (Division of Synthesis Research Laboratory, Dongbang FTL) ;
  • Lee, Gyung-Rak (Department of Biotechnology, Soonchunhyang University) ;
  • Kim, Seung-Han (Department of Biotechnology, Soonchunhyang University)
  • 투고 : 2012.01.26
  • 심사 : 2012.04.29
  • 발행 : 2012.04.30

초록

노루궁뎅이 버섯 균사체를 인진쑥 배지에 배양시킨 배양물(HEAC)을 여러 농도의 에탄올-물의 용액으로 추출하고, 쥐에서 위염 유발시약(0.15 M 염산-에탄올 용액)에 의한 위점막 손상에 대하여 추출물들의 위염 억제효과실험을 실시하였다. 그 중 80% 에탄올 추출물은 위염에 대하여 67.7%로 우수한 억제효과를 나타내었다. 용매별 분획으로 HEAC의 80%에탄올 추출물을 노르말 헥산, 염화메틸렌, 초산에틸, 노르말 부탄올과 증류수를 이용하여 5가지 분획으로 분리하였다. 그 결과, 노르말 헥산과 염화메틸렌 분획들이 위염에 대하여 우수한 억제효과를 나타내었다. 이에 따라 염화메틸렌 추출물에 대하여 GC/MS, HPLC, IR and NMR($^1H$, $^{13}C$)을 이용하여 생리활성 주성분의 구조를 확인한 결과 ethyl linoleate임을 확인하였다. 또한, HEAC의 80% 에탄올 추출물과 ethyl linoleate의 $ED_{50}$값이 각각 22.6과 6.4 mg/kg을 나타내어 대조약제인 stillen (44.2 mg/kg)과 selbex (46.5 mg/kg) 보다 우수한 억제효과가 있음을 확인하였다. 그러므로, HEAC의 80% 에탄올 추출물과 ethyl linoleate는 염산-에탄올에 의하여 유발된 위염에 대하여 우수한 억제효과를 가지고 있으며, 새로운 위염, 위궤양 치료제로 개발될 수 있을 것으로 기대된다.

The purpose of this study is to evaluate the gastric mucosal damage effect by Hericium erinaceus cultibated with Artemisia capillaris (HEAC) with 0.15 M HCl in ethanol in rats. Among them, 80% ethanol extract showed potent inhibitory effect (67.7%) on gastritis. Using solvent fractionation, 80% ethanol extract of HEAC was separated into five fractions with $n$-hexane, methylene chloride, ethyl acetate, $n$-butanol and water. As a result, fractions obtained with methylene chloride exhibited strong inhibitory effects on gastritis. With this result, the methylene chloride extract was analyzed by GC/MS, HPLC, IR and NMR($^1H$, $^{13}C$) to identify primary active components and the main component in the extract was identified as ethyl linoleate. The effective does ($ED_{50}$) values of 80% ethanol extract of HEAC and ethyl linoleate showed 22.6 and 6.4 mg/kg, respectively and these values were higher than those of stillen (44.2 mg/kg) and selbex (46.5 mg/kg). Therefore, the administration of 80% ethanol extract of HEAC and ethyl linoleate have a strong protective effect agasint the gastritis induced by HCl-ethanol and may be promising new drug for treating gastritis and gastric ulcer.

키워드

참고문헌

  1. S. Choi, Y. J. Lim and S. K. Park, "Risk factor analysis for metaplastic gastritis in Koreans", World J. Gastroenterol., 12, pp. 2584-2587, 2006. https://doi.org/10.3748/wjg.v12.i16.2584
  2. H. S. Youn, G. H. Ko, M. H. Chung, W. K. Lee, M. J. Cho and K. H. Rhee, "Pathogenesis and prevention of stomach cancer", J. Korean Med. Sci., 11, pp. 373-385, 1996. https://doi.org/10.3346/jkms.1996.11.5.373
  3. K. Huh, T. H. Kwon, U. S. Shin, W. B. Kim, B. O. Ahn, T. Y. Oh and J. A. Kim, "Inhibitory effects of DA-9601 on ethanol-induced gastro-hemorrhagic lesions and gastric xanthine oxidase activity inrats", J. Ethnopharmacol., 88, pp. 269-273, 2003. https://doi.org/10.1016/S0378-8741(03)00235-6
  4. E. B. Lee, O. J. Kim, S. S. Kang and C. C. Jeong, "Araloside A, an antiulcer constituent from the root bark of Aralia elata", Biol. Pharmac. Bull., 28, pp. 523-526, 2005. https://doi.org/10.1248/bpb.28.523
  5. E. B. Lee, "The effect of Artemisia Herba on gastric lesion and ulcers in rats with isolation of eupatilin", Unesco Regional Seminar on the Chemistry, Pharmacology and clinical use of flavonoid compounds, pp. 13-20, 1995.
  6. S. E. Lee, J. H. Jeong, D. G. Kim and W. S. Choi, "Inhibitory effect on aflatoxin B1-8,9-epoxide formation and anti-complementary activity of methanol extract from Hericium erinaceus cultivated with Artemisia iwayomogi" Food Sci. Biotechnol., 12, pp. 183-186, 2003.
  7. W. S. Choi, C. J. Kim, B. S. Park, S. E. Lee, G. R. Takeoka, D. G. Kim, X. L. Piao and J. H. Kim, "Inhibitory effect on proliferation of vascular smooth muscle cells and protective effect on CCl4-induced hepatic damage of HEAC extract" J. Ethnopharmacol., 100, pp. 176-179, 2005. https://doi.org/10.1016/j.jep.2005.02.037
  8. G. Schmeda-Hirschmann, J. A. Rodriguez and L. Astudillo, "Gastroprotective activity of the diterpene solidagenone and its derivatives on experimentally induced gastric lesions in mice", J. Ethnopharmacol., 81, pp. 111-115, 2002. https://doi.org/10.1016/S0378-8741(02)00054-5
  9. S. K. Kim, C. G. Son, C. H. Yun and S. H. Han, "Hericium erinaceum induces maturation of dendritic cells derived from human peripheral blood monocytes", Phytother. Res., 24, pp. 14-17, 2010. https://doi.org/10.1002/ptr.2849
  10. M. H. Yim, J. W. Shin, J. Y. Son, S. M. Oh, S. H. Han, J. H. Cho, C. K. Cho, H. S. Yoo, Y. W. Lee and C. G. Son, "Soluble components of Herium erinaceum induced NK cell activation via production of interleukin-12 in mice splenocytes", Acta. pharmacol. Sinica., 28, pp. 901-907 2007. https://doi.org/10.1111/j.1745-7254.2007.00577.x
  11. H. Xu, H. R. Wu, Z. Y. Shen and X. D. Chen, "Chemical analysis of Hericium erinaceum polysaccharides and effect of the polysaccharides on derma antioxidant enzymes, MMP-1 and TIMP-1 activities", Int. J. Biol. macromol., 2010.
  12. H. Kenmoku, T. Shimai, T. Toyomasu, N. Katon and T. Sassa, "Erinacine Q, a new erinacine from Hericium erinaceum, and its biosynthetic route to erinacine C in the basidomycete", Biosci. Biotechnol. Biochem., 66, pp. 571-575, 2002. https://doi.org/10.1271/bbb.66.571
  13. E. W. Lee, K. Shizuki, S. Hosokawa, M. Suzuki, H. Suganuma, T. Inkauma, J. Li, M. Ohinishi-Kameyama, T. Nagata, S. Furukawa and H. Kawagishi, "Two novel diterpenoids, erinacines H and I from the mycelia of Hericium erinaceum", Biosci. Biotechnol. Biochem., 64, pp. 2402-2405, 2000. https://doi.org/10.1271/bbb.64.2402
  14. S. G. Lee, "The therapeutic effect of Artemisia capillaris extract on hepatic damage induced by carbon tetrachloride in rats", J. Vet., 22, pp. 206-213, 2005.
  15. B. Y. Ahn, H. S. Hwang, S. H. Baek, J. S. Kwak, D. S. Choi and J. H. Han, "Desmutagenic effect of water extract from Artemisia capillaries THUMB on the mutagenicity of benzo[a]pyrene. Korean J. Biotechnol. Bioeng., 15, pp. 331-336, 2000.
  16. D. Hollander, W. J. Krause and J. Stachura, "Is linoleic acid (diethyl essential fatty acid-EFA) cytoprotective for the gastric mucosa?", Gastroenterol., 88, pp. 610-614, 1985.
  17. D. Hollander, A. Tarnawski and K. J. Ivey, "Arachidonic acid protection of rat mucosa against ethanol-induced injury", J. Lab. Clin. Med., 100, pp. 296-307, 1982.
  18. M. H. Pillinger, N. Marjanovic, S. Y. Kim, J. U. Scher, P. Izmirly, S. Tolani, V. Dinsell, Y. C. Lee, M. J. Blaser and S. B. Avramson, "Matrix metalloproteinase secretion by gastric epithelial cells is regulated by E prostaglandins and MAPKs", The ournal of biological chemistrry, Vol. 280, No. 11, pp. 9937-9979, 2005.
  19. J. S. Kim, K. Okamoto, S. Arima and B. K. Rubin, "Vasoactive intestinal peptide stiulates mucus secretion, but nitric oxide has no effect on mucus secretion in the ferret trachea.", J. Appl. Physiol, 101(2), 486-91, 2006. https://doi.org/10.1152/japplphysiol.01264.2005
  20. J. I. Isenberg, D. L. Hogan, M. A. Koss and J. A. Selling, "Human duodenal mucosal bicarbonate secretion. Evidence for basal secretion and stimulation of hydrochloric acid and a synthetic prostaglandin E1", Gastroenterol., 91, pp. 370-378, 1986. https://doi.org/10.1016/0016-5085(86)90571-8
  21. B. M. Peskar, K. Ehrlich and B. A. Peskar, "Interaction of cyclooxygenase-2 inhibitors and salicylate in gastric mucosal damage.", European Journal of Pharmacology 434, pp. 65-70, 2002. https://doi.org/10.1016/S0014-2999(01)01524-2
  22. T. Matsuhisa and T. Rsukui, "Relation between reflux of bile acids into the stomach and gastric mucosal atrophy, intestinal metaplasia in biopsy specimens.", J. Clin. Biochem. Nutr, pp. 1-5, 2011.
  23. A. E. Ligha and H. B. Fawehinmi, "Protection by liquorice in alcohol induced gastric mucosa damage", Pak. J. Nutr., 8(10), pp. 1532-1536, 2009. https://doi.org/10.3923/pjn.2009.1532.1536
  24. A. M. nielsen, J. Hillingso, H. Frakiaer, K. Bukhave and J. R. madsen, "Gastric bicar-bonate secretion and release of prostaglandin E2 Are increased in duodenal ulcer patients but not on helicobacter pylori-positive healthy subjects.", Scand. J. Gastroenterol, Vol. 31, No. 1, pp. 38-43, 1996. https://doi.org/10.3109/00365529609031624
  25. S. M. Park, B. C. Yoo, H. R. Lee, H. Chung, Y. S. Lee, "Distribution of prostaglandin E2 in gastric and duodenal mucosa: possible role in the pathogenesis of peptic ulcer.", Korean J Intern. Med, 7(1), pp. 1-8, 1992. https://doi.org/10.3346/jkms.1992.7.1.1
  26. T. K. Razdan, B. Qadri, S. Harkar and E. S. Waight, "Chromenes and coumarins from Skimmia laureola", Phytochem., 26, pp. 2063-2069, 1987. https://doi.org/10.1016/S0031-9422(00)81759-8