DOI QR코드

DOI QR Code

삼황사심탕(三黃瀉心湯) 추출물의 lipopolysaccharide 유도에 의한 염증 조절과 대식세포 활성에 대한 연구

Effect of Samhwangsashimtang Extract on Lipopolysaccharide-Stimulated Inflammatory Response and Macrophage Activity

  • 강희 (경희대학교 동서의학대학원) ;
  • 권한올 (경희대학교 동서의학대학원) ;
  • 소형진 (경희대학교 동서의학대학원) ;
  • 이정민 (경희대학교 동서의학대학원) ;
  • 류재환 (경희대학교 동서의학대학원) ;
  • 최호영 (경희대학교 한의과대학 본초학교실)
  • Kang, Hee (Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Kwon, Han-Al (Graduate School of East-West Medical Science, Kyung Hee University) ;
  • So, Hyung-Jin (Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Lee, Jeong-Min (Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Lew, Jae-Hwan (Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Choi, Ho-Young (Dept. of Herbology, College of Oriental Medicine, Kyung Hee University)
  • 투고 : 2012.10.26
  • 심사 : 2012.11.05
  • 발행 : 2012.11.30

초록

Objectives : Samhwangsashim-tang(SHSST), a mixture of Rhei radix et rhizoma, Scutellariae radix, and Coptidis rhizoma, has been regarded as being able to treat bleeding, gastric discomfort, dry mouth, insomnia and purpura due to Blood Heat. Currently, this herbal formula is applied to gastritis, gastric ulcer, hypertension, atherosclerosis or other types of vascular inflammatory disorders. Methods : We extracted this herbal mixture with 30% ethanol and examined for its effects on systemic inflammatory responses and in vitro macrophage activity. Mice were orally given to SHSST for 7 days and then lipopolysaccharide(LPS) was intraperitoneally injected. Tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) levels in serum were measured 1 h after LPS challenge. Peritoneal macrophages were isolated from thioglycollate-injected mice and used for in vitro cellular activity. Cell death was measured using the MTT method and annexin V/propidium iodide staining. LPS-stimulated signaling molecules necessary for TNF-${\alpha}$ expression were determined by Western blotting. Results : Oral administration of SHSST for 7 days resulted in a significant reduction in LPS-stimulated TNF-${\alpha}$ release into serum. In vitro treatment of SHSST was cytotoxic in a concentration-dependent manner. However, SHSST caused a concentration-dependent reduction in necrosis and increase in apoptosis in mouse peritoneal macrophages. SHSST inhibited the activation of NF-${\kappa}B$, p38 and JNK signaling molecules in response to LPS. Conclusion : Taken together, our results demonstrated that SHSST was effective in lowering LPS-stimulated TNF-${\alpha}$ serum levels, possibly through its modulation of NF-${\kappa}B$, p38 and JNK in macrophages.

키워드

참고문헌

  1. Kim JB. A treatise on Essential prescriptions of the Golden coffer (Gum-Gye-Yo-Rak-Byun-Suk). Hanyunmoonhwasa. 2003 : 449-50.
  2. Lin WC, Tan TW. The role of gastric muscle relaxation in cytoprotection induced by san-huang-xie-xin-tang in rats. J Ethnopharmacol. 1994 ; 44(3) : 171-9. https://doi.org/10.1016/0378-8741(94)01184-2
  3. Chung MH, Han SK. Effect of composite preparation of crude drugs on experimentally induced hyperlipidemia in rats - Sam Whang Sasim Tang and Whang Ryun Haedok Tang. Kor J Pharmacogn. 1996 ; 27(4) : 397-407.
  4. Onat A. Metabolic syndrome: nature, therapeutic solutions and options. Expert Opin Pharmacother. 2011 ; 12(12) : 1887-990. https://doi.org/10.1517/14656566.2011.585462
  5. Lundberg AM, Hanson GK. Innate immune signals in atherosclerosis. Clinical Immunol. 2010 ; 134 : 5-24. https://doi.org/10.1016/j.clim.2009.07.016
  6. Gordon S. The macrophage: past, present and future. Eur J Immmunol. 2007 ; 37 : S9-S17. https://doi.org/10.1002/eji.200737638
  7. Kim EJ, Kim HY, Lee JY, Lee JK, Kim SJ, Choi KM, Kang DA. Effect of Samhwangsasim-tang, Samigangap-tang and Bangtan-tang on blood pressure in strok prone spontaneously hypertensive rats. Korean J Herbol. 2011 ; 26(1) : 75-80.
  8. Kim JB, Kwon OK, Son CW, Shin HM. Vasodilatory effects of Samhwangsasim-tang on vascular smooth muscle. Korean J Oriental Physiology & Pathology. 2004 ; 8(5) : 1382-6.
  9. Lo YC, Tsai PL, Huang YB, Shen KP, Tsai YH, Wu YC, Lai YH, Chen IJ. San-Huang-Xie-Xin-Tang reduces lipopolysaccharide-induced hypotension and inflammatory mediators. J Ethnopharmacol. 2005 ; 96(1-2) : 99-106. https://doi.org/10.1016/j.jep.2004.09.023
  10. Lo YC, Lin YL, Yu KL, Lai YH, Wu YC, Ann LM, Chen IJ. San-Huang-Xie-Xin-Tang attenuates inflammatory responses in lipopolysaccharide-exposed rat lungs. J Ethnopharmacol. 2005 ; 101(1-3) : 68-74. https://doi.org/10.1016/j.jep.2005.03.015
  11. Tsai HH, Chen IJ, Lo YC. Effects of San-Huang-Xie-Xin-Tang on U46619-induced increase in pulmonary arterial blood pressure. J Ethnopharmacol. 2008 ; 117(3) : 457-62. https://doi.org/10.1016/j.jep.2008.02.024
  12. Wang YS, Lin RT, Cheng HY, Yang SF, Chou WW, Juo SH. Anti-atherogenic effect of San-Huang-Xie-Xin-Tang, a traditional Chinese medicine, in cultured human aortic smooth muscle cells. J Ethnopharmacol. 2011 ; 133(2) : 442-7. https://doi.org/10.1016/j.jep.2010.10.018
  13. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular Biology of the Cell (5th ed). Garland Science. 2008 : 1117.
  14. Hayden MS, Ghosh S. Signaling to NF-kappa B. Genes Dev. 2004 ; 18 : 2195-224. https://doi.org/10.1101/gad.1228704
  15. Medzhitov R, Horng T. Transcriptional control of the inflammatory response. Nat Rev Immuno. 2009 ; 9 : 692-703. https://doi.org/10.1038/nri2634
  16. Brook M, Sully G, Clark AR, Saklatvala J. Regulatin of tumour necrosis factor $\alpha$ mRNA stabilit by the mitogen-activated protein kinase p38 signalling cascade. FEBS Lett. 2000 ; 483 : 57-61. https://doi.org/10.1016/S0014-5793(00)02084-6
  17. Swantek JL, Cobb MH, Geppert TD. Jun N-terminal kinase/stress-activated kinase (JNK/SAPK) is required for lipopolysaccharide stimulation of tumor necrosis factor alpha(TNF-${\alpha}$) translation: Glucocorticoids inhibit TNF-${\alpha}$ translation by blocking JNK/SAPK. Mol Cell Biol. 1997 ; 17(11) : 6274-82. https://doi.org/10.1128/MCB.17.11.6274
  18. Abbas AK, Lichtman AH, Pillai S. Cellular and Molecular Immunology. Saunders. 2009 : 273-8.
  19. Liou SF, Hsu JH, Liang JC, Ke HJ, Chen IJ, Wu JR, Yeh JL. San-Huang-Xie-Xin Tang protects cardiomyocytes against hypoxia/reoxygenation injury via inhibition of oxidative stress-induced apoptosis. J Nat Med. 2012 ; 66(2) : 311-20. https://doi.org/10.1007/s11418-011-0592-0
  20. Shia CS, Hou YC, Juang SH, Tsai SY, Heish PH, Ho LC, Lee Chao PD. Metabolism and pharmacokinetics of San-Huang-Xie-Xin-Tang, a polyphenol-rich Chinese medicine formula, in rats and ex-vivo antioxidant activity. Evid Med complement Alternat Med. 2011 ; 2011 : 721293.