The Journal of Internal Korean Medicine (대한한방내과학회지)

The Society of Internal Korean Medicine (대한한방내과학회)
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Anti-inflammatory activity of the water extract of Polygala tenuifolia Willd

원지(遠志)의 항염증 작용에 대한 연구

  • Oh, Hyun-Suk (Dept. of Internal Medicine, College of Oriental Medicine, Sang-Ji University) ;
  • Kim, Byoung-Woo (Dept. of Internal Medicine, College of Oriental Medicine, Sang-Ji University)
  • 오현석 (상지대학교부속한방병원 내과) ;
  • 김병우 (상지대학교부속한방병원 내과)
  • Published : 2013.06.30
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Abstract

Objectives : This study was designed to investigate the cellular and molecular mechanisms of anti-inflammatory activity of the water extract of Polygala tenuifolia Willd. (Pt-WE). Methods : Using lipopolysaccharide (LPS)-stimulated murine RAW264.7 cells, we examined inflammatory mediators such as nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2 and prostaglandin $E_2$ ($PGE_2$). Also, the inhibitory effect of Pt-WE on the activity of activator protein 1 (AP-1) and upstream signaling molecules was evaluated. To assess the protective effect of Pt-WE on hydrochloride/ethanol (HCl/EtOH)-induced gastric ulcer in mice, we compared Pt-WE (200 mg/kg) with ranitidine (50 mg/kg) treated mice's gastric mucosa, based on gross observations. Results : Pt-WE inhibited LPS-induced production of NO, $PGE_2$ in a dose-dependent manner, without causing cytotoxicity. Pt-WE suppressed AP-1 activation by reducing generations of both c-Jun and c-Fos. In addition, Pt-WE inhibited the p-MKK 4/7 (mitogen-activated protein kinase kinase 4/7) and p-JNK (c-Jun N-terminal kinase) 1 in LPS-stimulated RAW264.7 cells. HCl/EtOH-induced gastric ulcer lesions were inhibited by pre-treatment of Pt-WE based on gross observations. In addition, Pt-WE decreased the phosphorylation level of JNK. Conclusions : These results demonstrate that Pt-WE has anti-inflammatory and gastroprotective effects. Thus, Pt-WE may be used widely in treatment of not only neurodegenerative diseases but also inflammatory diseases.

Keywords

References

  1. Woods JA, Vieira VJ, Keylock KT. Excercise, inflammation, and innate immunity. Neurol Clin 2006;24:585. https://doi.org/10.1016/j.ncl.2006.03.008
  2. Tetley TD. Inflammatory cells and chronic obstructive pulmonary disease. Current Drug Targets - Inflammation & Allergy 2005;4(6) :607-18. https://doi.org/10.2174/156801005774912824
  3. Newton K, Dixit VM.. Signaling in Innate Immunity and Inflammation. Cold Spring Harb Perspect Biol 2012;4:1-19.
  4. 전국한의과대학공동교재편찬위원회공저. 본초학 (本草學). 서울: 永林社; 2007, p. 532-3.
  5. 강병수, 김영판. 방제의 체계적 구성을 위한 임상 배합본초학. 2판. 서울: 永林社; 1996, p. 309-11.
  6. 황시영, 강형원, 류영수. 遠志에 의한 腦星狀細 胞로부터 炎症性細胞活性物質分泌의 抑制效 果에 關한 硏究. 동의신경정신과학회지 1999;10(1) :95-108.
  7. 이수배, 성낙술, 이영종. 遠志가 NMDA로 유발 된 신경세포 손상에 미치는 효과. 대한본초학회 지 2005;20(2):115-25.
  8. Cheong MH, Lee SR, Yoo HS, Jeong JW, Kim GY, Kim WJ, et al. Anti-inflammatory effects of Polygala tenuifolia root through inhibition of NF-kB activation in lipopolysacchraride-induced BV2 microglial cells. J Ethnopharmacol 2011; 137:1402-8. https://doi.org/10.1016/j.jep.2011.08.008
  9. Mosmaan T. Rapid colorimetric assay for cellular growth and survival : Application to proliferation and cytotoxicity assays. J Immunological Methods 1983;65:55-63. https://doi.org/10.1016/0022-1759(83)90303-4
  10. Cho JY, Baik KU, Jung JH, Park MH. In vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappa. Eur J Pharmacol 2000;398:399-407. https://doi.org/10.1016/S0014-2999(00)00337-X
  11. 센팅, 이용진, 조재열. 반지련(Scutellaria barbata D. Don) 추출물이 lipopolysaccharide에 의해 활 성화된 대식세포에 미치는 영향. 한국약용작물 학회지 2008;16(5):313-9.
  12. Lee YG, Lee WM, Kim JY, Lee JY, Lee IK, Yun BS, et al. Src kinase-targeted anti-inflammatory activity of davallialactone from Inonotus xeranticus in lipopolysaccharide-activated RAW264.7 cells. Br J Pharmacol 2008;154:852-63.
  13. Miernyk JA, Thelen JJ. Biochemical approaches for discovering protein-protein interactions. Plant J 2008;53:597-609. https://doi.org/10.1111/j.1365-313X.2007.03316.x
  14. Ren L, Emery D, Kaboord B, Chang E, Qoronfleh MW. Improved immunomatirx methods to detect protein: protein interactions. J Biochem Biophys Methods 2003;57:143-57. https://doi.org/10.1016/S0165-022X(03)00105-2
  15. Lal A, Haynes SR, Gorospe M. Clean western blot signals from immunoprecipitated samples. Mol Cell Probes 2005;19(6):385-8. https://doi.org/10.1016/j.mcp.2005.06.007
  16. Oyagi A, Ogawa K, Kakino M, Hara H. Protective effects of a gastrointestinal agent containing Korean red ginseng on gastric ulcer models in mice. BMC Complement Altern Med 2010;10:45. https://doi.org/10.1186/1472-6882-10-45
  17. Ganguly K, Swarnakar S. Chronic gastric ulceration causes matrix metalloproteinases-9 and -3 augmentation: Alleviation by melatonin. Biochimie 2012;94(12):2687-98. https://doi.org/10.1016/j.biochi.2012.08.004
  18. 이지혜, 이봉효, 김창열, 노성수. 遠志의 화학성 분과 약리효능에 대한 한의학적 고찰. 韓藥應 用學會誌2010;10(1):25-33.
  19. 신홍중, 조연행, 조창환, 오민석. 方藥合編 中 遠志및 石菖蒲를 포함한 處方에 대한 考察. 대 전대학교 한의학연구소 논문집 2006;15(2):231-8.
  20. 허준. 동의보감. 초판 4쇄. 경남 하동: 동의보감 출판사; 2010, p. 270, 896-7, 1545, 1550.
  21. Taylor EL, Megson IL, Haslett C, Rossi AG. Nitric oxide; a key regulator of myeloid inflammatory cell apoptosis. Cell Death Differ 2003;10:418-30. https://doi.org/10.1038/sj.cdd.4401152
  22. Udou T, Hachisuga T, Tsujioka H, Kawarabayashi T. The Role of c-Jun Protein in Proliferation and Apoptosis of the Endometrium throughout the Menstrual Cycle. Gynecol Obstet Invest 2004;57(3):121-6. https://doi.org/10.1159/000075701
  23. Monje P, Hernández-Losa J, Lyons RJ, Castellone MD, Gutkind JS. Regulation of the transcriptional activity of c-Fos by ERK. A novel role for the prolyl isomerase PIN1. J Bio Chem 2005;280(42): 35081-4. https://doi.org/10.1074/jbc.C500353200
  24. Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, et al. Mitogen -activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 2001;22(2):153-83.
  25. Waetzig V, Herdegen T. Context-specific inhibition of JNKs: overcoming the dilemma of protection and damage. Br J Pharmacol 2005;26(9):445-61.
  26. JM Kyriakis, J Avruch. Mammalian mitogenactivated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 2001;81:807-69.
  27. Ip YT, Davis RJ. Signal transduction by the c-Jun N-terminal kinase(JNK)-from inflammation to development. Curr Opin Cell Biol 1998;10(2) :205-19. https://doi.org/10.1016/S0955-0674(98)80143-9
  28. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, et al. Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2006;127(3):635-48. https://doi.org/10.1016/j.cell.2006.09.026
  29. Derijard B, Raingeaud J, Barrett T, Wu IH, Han J, Ulevitch RJ, et al. Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms. Science 1995; 269(5220):17.
  30. Kondo M, Osada H, Uchida K, Yanagisawa K, Masuda A, Takagi K,et al. Molecular cloning of human TAK1 and its mutational analysis in human lung cancer. Int J Cancer 1998;75(4) :559-63. https://doi.org/10.1002/(SICI)1097-0215(19980209)75:4<559::AID-IJC11>3.0.CO;2-4
  31. Akiyama S, Yonezawa T, Kudo TA, Li MG, Wang H, Ito M, et al. Activation Mechanism of c-Jun Amino-terminal Kinase in the Course of Neural Differentiation of P19 Embryonic Carcinoma Cells. J Biol Chem 2004;279(35) :36616-20. https://doi.org/10.1074/jbc.M406610200
  32. Kovalenko PL, Kunovska L, Chen J, Gallo KA, Basson MD. Loss of MLK3 signaling impedes ulcer healing by modulating MAPK signaling in mouse intestinal mucosa. Am J Physiol Gastrointest Liver Physiol 2012;303(8):G951-60. https://doi.org/10.1152/ajpgi.00158.2012