A Comparative Study of Pyeongwi-san, Ijin-tang and Pyeongjintang Extracts on Indomethacin-Induced Gastric Mucosal Lesions in Mice

Indomethacin으로 유발된 생쥐의 위점막 손상에 대한 평위산(平胃散), 이진탕(二陳湯) 및 평진탕(平陳湯)의 비교연구

  • Ji, Hyeon-Chyol (Dept. of Internal Medicine, College of Korean Medicine, Sangji University) ;
  • Baek, Tae-Hyeun (Dept. of Internal Medicine, College of Korean Medicine, Sangji University)
  • 지현철 (상지대학교 부속한방병원 내과학교실) ;
  • 백태현 (상지대학교 부속한방병원 내과학교실)
  • Received : 2011.02.21
  • Accepted : 2011.03.16
  • Published : 2011.03.30

Abstract

Objectives: This study was performed to investigate the protective and treating efficacy of Pyeongwi-san, Ijin-tang, and Pyeongjin-tang extracts to the mice with gastric mucosal lesions induced from indomethacin. Methods: In order to verify protective and treating efficacy of Pyeongwi-san, Ijin-tang, and Pyeongjin-tang extracts to the mice with gastric mucosal lesions induced from indomethacin, I administered the extracts of these prescriptions to three group, and induced gastric mucosal lesion by indomethacin, and then I observed the gastric mucosal morphology of stomach, changes from stress resulting from HSP70, changes of gastro-protection (mucous barrier, COX-1). After I observed the anti-oxidant effect, and anti-inflammation effect (IKK mRNA, iNOS mRNA, COX-2 mRNA) in vitro, I induced gastric mucosal lesion by indomethacin, and administered the extracts of each prescriptions to three group, and then I observed the gastric mucosal morphology, anti-inflammation effect to mucosa (NF-${\kappa}$B, iNOS, COX-2) in vivo. Results & Conclusions: 1. Hemorrhagic erosion and damaged mucus secreting cell, positive responses to HSP70 were decreased in all the before-gastric-mucosal-lesion-induced groups, compared to non-extract administered group. The effects were good in the order of Pyeongwi-san extracts administered group, Pyeongjin-tang extracts administered group and Ijin-tang extracts administered group. 2. In all the before-gastric-mucosal-lesion-induced groups, gastro- protection functions (mucous barrier, COX-1) were significant. The effects were good in the order of Pyeongwi-san extracts administered group, Pyeongjin-tang extracts administered group and Ijin-tang extracts administered group. 3. Anti-oxidant effect was significant in Pyeongwi-san extracts, Ijin-tang extracts and Pyeongjin-tang extracts. The effects were good in the order of Pyeongjin-tang extracts, Pyeongwi-san extracts and Ijin-tang extracts. 4. The anti-inflammation effects in vitro were good in Pyeongwi-san extracts, Ijin-tang extracts and Pyeongjin-tang extracts. Especially Pyeongjin-tang extracts showed the most prominent results. Damaged mucus secreting cells and the positive reactions of NF-${\kappa}$B, iNOS, COX-2 in vivo were decreased in after-gastric-mucosal-lesion-induced groups compared to non-extract administered group. The effects were good in the order of Pyeongjin-tang extracts administered group, Pyeongwi-san extracts administered group and Ijin-tang extracts administered group. These results show that Pyeongwi-san, Ijin-tang and Pyeongjin-tang are effective on both in protecting and treating the gastric mucosal membrane. Pyeongwi-san is more effective than other prescriptions, in protecting gastric mucosal membrane, and Pyeongjin-tang is more effective in treating gastric mucosal lesion.

Keywords

References

  1. 김정룡. 소화기계 질환. 서울:일조각. 2005:206-14.
  2. 순천향대학교 의과대학 소화기연구소. 소화기학. 서울:고려의학. 2004:225-28.
  3. 대한소화기학회. 소화성궤양. 서울:군자출판사. 2002:19-32
  4. 전국한의과대학 비계내과학교실. 脾係內科學. 서울:군자출판사. 2008:333-39.
  5. 危北海, 越榮萊, 李乾构. 中醫脾胃學說應用硏究. 北京:北京出版社. 1993:203-10.
  6. 陳貴廷, 楊思澍. 實用中西醫結合診斷治療學. 北京:中醫藥科技出版社. 1991:437-41.
  7. 전국한의과대학 병리학교실. 한방병리학. 서울: 일중사. 2004:69-71, 150-2, 173-4.
  8. 김갑성, 김명동, 김윤범, 김장현, 김중호, 이원철 외. 東西醫學臨床總書. 서울:정담. 2001:495-500.
  9. 尹吉榮. 東醫臨床方劑學. 서울:成輔社. 2002:58-9, 72, 85-90.
  10. 배병철. 표준임상방제학. 서울:成輔社. 1995:19, 211-3, 411.
  11. 배동주. 생쥐의 위점막 손상에 대한 이진탕 사군 자탕 및 육군자탕의 비교 연구[박사학위논문]. 원주:상지대학교대학원. 2005.
  12. 박정한. Indomethacin으로 유발된 생쥐의 위점막 손상에 대한 이진탕 향사이진탕 및 내소산의 비교연구[박사학위논문]. 원주:상지대학교대학원. 2008.
  13. Kong KH, Baik. TH. .Effects of Hyangsayukgunjatang Extract on Indomethacin-Induced Gastric Lesions. Journal of korean internal medicine. 2001;22(4):589-99.
  14. 이재준. Indomethacin으로 損傷된 생쥐의 胃粘膜에 對한 平胃散 香 砂平胃散 大和中飮의 效果[박사학위논문]. 원주:상지대학교 대학원. 2005.
  15. Park JH, Baik TH. Effects of Pyungjintang Extract on Indomethacin-induced gastric mucosal lesions in mice. Journal of korean oriental medicine. 2005;26(3):215-27.
  16. 黃度淵. 方藥合編. 서울:南山堂. 2001:142, 190, 212.
  17. 張介賓. 景岳全書. 上卷. 서울:大星文化社. 1998: 355, 635.
  18. Choi HM, Lim SW. Effects of Hyangsapyeongwisan on Gastric Mucosal Lesions Induced by Indomethacin. Journal of korean internal medicine. 2004;25(3):518-28.
  19. Baik TH. Effects of Pyeongwibunsoeum Extract on Indomethacin-induced Gastric Mucosal lesions. Journal of korean oriental medicine. 2003;24(2): 94-108.
  20. David Y. Graham : NSAID ulcers : prevalence and prevention. Mod Rheumatol. 2000;10:2-7. https://doi.org/10.1007/s101650070031
  21. Tetsuo Arakawa, Kazuhide Higuchi, Takashi Fukuda, Yasuhiro Fujiwara, Kenzo Kobayashi, d Tetsuo kuroki. Prostaglandins in the stomach; an update. J. Clin. Gastroenterol. 1998;27:1-11.
  22. Schoen R. T, Vender R. J. Mechanism of NASID induced gastric damage. AM, J. Med. 1989;86: 449-58. https://doi.org/10.1016/0002-9343(89)90344-6
  23. Byron Crye, Michael B. Kimmey. Gastrointestinal side effects of nonsteroidal antiinflammatory drug. Am J med. 1998;105:20s-30s.
  24. Lee S. Siomon. Biology and toxic effects of nonsteroidal anti-inflammatory drugs. Current Opinion in Rheumatology. 1998;10:153-58. https://doi.org/10.1097/00002281-199805000-00001
  25. Byron Cryer, Andre Dubois. The advent of highly selective inhibitors of cyclooxygenase-a review. Prostaglandins & other Lipid Mediators. 1998;56:341-61. https://doi.org/10.1016/S0090-6980(98)00064-1
  26. Choitsu Sakamoto. Roles of COX-1 and COX-2 in gastrointestinal pathophysiology. J Gastroenterol. 1998;33:618-24. https://doi.org/10.1007/s005350050147
  27. De Maio A. The heat-shock response. New Horiz. 1995;2:198-207.
  28. Gonzalez M. F., Shiraishi K., Hisanaga K., Sagar S. M., Mandabach M., Sharp F. R. Heat shock protein as markers of neuronal injury. Mol. Brain Res. 1989;6:93-100. https://doi.org/10.1016/0169-328X(89)90033-8
  29. Vass K., Beger M. L., Nowak T. S., Jr Lassmann H. Induction of stress protein HSP70 in nerve cell after status epilepticus in the rat. Neurosci Lett. 1989;100:259-64. https://doi.org/10.1016/0304-3940(89)90695-2
  30. Bergstedt K., Hu B. R., Weiloch T. Initiation of protein synthesis and heat shock protein-72 expression in the rat brain following sereve insulin induced hypoglycemia. Acta Neuropathol. 1989;86:259-64.
  31. Valazquez J. M. and Lindquist S. H. Hsp 70 - Nuclear concentration during enviromental stress and cytoplasmic stroage during recovery. Cell. 1984;36:655-622. https://doi.org/10.1016/0092-8674(84)90345-3
  32. Maulik N., Engelman R. M., Wei Z., Liu X., Rousou J. A., Flack J. E., et al. Drug-induced heat-shock preconditioning improves postischemic ventricular recovery after cardiopulmonary bypass. Circulation. 1995;92:381-88. https://doi.org/10.1161/01.CIR.92.9.381
  33. Maulik N., Wei Z., Liu X., Engelman R. M., Rousou J. A., Das D. K. Improvedpostischemic ventricular functional recovery by amphetamine is linked with its ability to induce heat shock. Mol. cell. Biochem. 1994;137:17-24. https://doi.org/10.1007/BF00926035
  34. Criag E. A., Gambill B. D., Nelson R. J. Heat shock protein: molecular chaperone of protein biogenesis. Microbiol Rev. 1993;57:402-14.
  35. Baeuerle P. A., Baltimore D. $NF{\kappa}B$ - Ten years after. 1996;Cell. 87:13-20. https://doi.org/10.1016/S0092-8674(00)81318-5
  36. Baeuerle P. A. : $I{\kappa}B-NF-{\kappa}B$ structure: at the interface of inflammation control. Cell. 1998;95: 729-31. https://doi.org/10.1016/S0092-8674(00)81694-3
  37. Anggard E. Nitric oxide: mediator, murderer, and medicine. Lancet. 1994;9:1199-206.
  38. Radi R., Beckman J. S., Bush K. M., Freeman B. A. Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys. 1991; 1;288(2):481-7.
  39. Villa L. M., Salas E., Darley-Usmar V. M., Radomski M. W., Moncada S. Peroxynitrite induces both vasodilatation and impaired vascular relaxation in the isolated perfused rat heart. Proc Natl Acad Sci USA. 1994;20;91(26):12383-7.
  40. Groszmann, R.J. Hyperdynamic state in chronic liver diseases. J Hepatol. 1993;17(2):S38-40.
  41. H. J. RothkӦtter, R. Pabst, M. Bailey. Lymphocyte migration in the intestinal mucosa : entry, transit and emigration of lymphoid cells and the influence of antigen. Vetrinary Immuno immunopath. 1999;72:157-65. https://doi.org/10.1016/S0165-2427(99)00128-2