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Inhibitory Effect of Water Extract from Dojuksan on LPS-induced Proinflammatory Cytokines Production in RAW 264.7 Cells

LPS로 자극한 RAW 264.7 세포에서 염증성세포활성물질 생산에 미치는 도적산(導赤散) 물 추출의 억제 효과

  • Kim, Ji-Eun (Department of Oriental Pharmacy, College of Pharmacy, Wonkwang Oriental Medicines Research Institute, and Institute of Biotechnology, Wonkwang University) ;
  • Kim, Sung-Bae (Department of Oriental Pharmacy, College of Pharmacy, Wonkwang Oriental Medicines Research Institute, and Institute of Biotechnology, Wonkwang University) ;
  • Kang, Ok-Hwa (Department of Oriental Pharmacy, College of Pharmacy, Wonkwang Oriental Medicines Research Institute, and Institute of Biotechnology, Wonkwang University) ;
  • Shin, In-Sik (Department of Oriental Pharmacy, College of Pharmacy, Wonkwang Oriental Medicines Research Institute, and Institute of Biotechnology, Wonkwang University) ;
  • Kang, Suk-Hoon (Department of Oriental Pharmacy, College of Pharmacy, Wonkwang Oriental Medicines Research Institute, and Institute of Biotechnology, Wonkwang University) ;
  • Lee, Seung-Ho (Department of Rehabilitative Therapy in Oriental Medicine, Gimcheon University) ;
  • Kwon, Dong-Yeul (Department of Oriental Pharmacy, College of Pharmacy, Wonkwang Oriental Medicines Research Institute, and Institute of Biotechnology, Wonkwang University)
  • 김지은 (원광대학교 약학대학 한약학과, 원광한약연구소, 원광생명공학연구소) ;
  • 김성배 (원광대학교 약학대학 한약학과, 원광한약연구소, 원광생명공학연구소) ;
  • 강옥화 (원광대학교 약학대학 한약학과, 원광한약연구소, 원광생명공학연구소) ;
  • 신인식 (원광대학교 약학대학 한약학과, 원광한약연구소, 원광생명공학연구소) ;
  • 강석훈 (원광대학교 약학대학 한약학과, 원광한약연구소, 원광생명공학연구소) ;
  • 이승호 (김천대학교 한방재활학과) ;
  • 권동렬 (원광대학교 약학대학 한약학과, 원광한약연구소, 원광생명공학연구소)
  • Received : 2013.04.22
  • Accepted : 2013.05.23
  • Published : 2013.05.30

Abstract

Objectives : DojukSan is known to be effective for treating a urinary diseases and stomatitis. However, there has been a lack of studies regarding the effects of Dojuksan on the inflammatory activities and effector inflammatory disease mechanism about macrophage before is not known. To elucidate the molecular mechanisms of Dojuksan water extract (DJS) on pharmacological and biochemical actions in inflammation, we examined the effect of DJS on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophages. Methods : In the present study, pro-inflammatory cytokine production was determined by performing enzyme-linked immunosorbent assay, reverse transcription polymerase chain reaction, and western blot analysis to measure the activation of MAPKs. Cells were treated with 200 ng/mL of LPS 1 h prior to the addition of DJS. Cell viability was measured by MTS assay. The investigation focused on whether DJS inhibited nitric oxide (NO) and prostaglandin E2 ($PGE_2$) productions, as well as the expressions of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6) and mitogen-activated protein kinases (MAPKs) in LPS-stimulated RAW 264.7 cells. Results : We found that DJS inhibited LPS-induced NO, $PGE_2$ and IL-6 productions as well as the expressions of iNOS and COX-2. Furthermore, DJS suppressed the LPS-induced phosphorylation of p38 MAPK and c-Jun NH2-protein kinase (JNK). Conclusions : These results suggest that DJS has inhibitory effects on LPS-induced $PGE_2$, NO, and IL-6 production, as well as the expressions of iNOS and COX-2 in the murine macrophage. These inhibitory effects occur through blockades on the MAPKs phosphorylation.

Keywords

References

  1. Qian Y. Xiaoeryaozhengzhijie. Taipei : Cosmos Medical Publishing Co. 1962 : 14-25.
  2. Dongeuigwahakwon. Dongeuicheobangdaejeon 2. Seoul : Yeogang Publishing Co. 1993 : 1082
  3. Professors of Oriental Pharmacy Prescription (co-authored). Bangjehak. Seoul : Younglimsa. 2008 : 191
  4. Yun HJ, Yun YG, Kang SS. Effects of Dojuksan on the Renal Function in Rats. J Oriental Med Surg Ophthalmol Otolaryngol. 1999 ; 12.
  5. Jin YS, Koo BH. A Study of the Antipyretic, Diuretic, and Anticonvulsive Effects of Kamidojeoksan Used in the Febrile Disease of Pediatrics. K. H. Univ. O MED J. 1981 ; 4 : 235-41.
  6. Sin HS, Oh YS, Kim YS, Seo lC. Effect of Gamidojeok-san on Hypertension. Korean J Oriental Physiol Palthol. 2004 ; 18 : 1710-13.
  7. Seo JY, Choi AR, Koo DM. Effect of Hyeongbangdojeok-san on Acute Cocaine-induced Behavioral Effect and Immediate Early Gene Expression in Rats. J of Sasang Const Med. 2010 ; 22 : 65-76.
  8. Kim EY, Kim JW. The Effect of Hyungbangdojucksan-Gami and Kamsuchunilhwan on the Obesity in the Rats. J of Sasang Const Med. 2000 ; 12 : 184-194.
  9. Ahn SH, Kim JT. Sopungdojeok-San Inhibits Atopy-liked Dermal Inflammation through Regulation of iNOS mRNA Expresssion & NO production. Korean J Oriental Med Prescription. 2007 ; 15 : 199-211.
  10. Park MC, Kwon J, Jung HS, Lee KG. Effects of Dojeokseungki-Tang on the apoptosis of leukemia cell. Korean J Oriental Physiol Palthol. 2003 ; 17 : 338-45.
  11. Cho W, Nam JW, Kang HJ, Windono T, Seo EK, Lee KT. Zedoarondiol isolated from the rhizoma of Curcuma heyneana is involved in the inhibition of iNOS, COX-2 and pro-inflammatory cytokines via the downregulation of NF-$\kappa B$ pathway in LPS-stimulated murine macrophages. Int Immunopharmacol. 2009 ; 9 : 1049-57. https://doi.org/10.1016/j.intimp.2009.04.012
  12. Nathan C. Inducible nitric oxide synthase: what difference does it make?. J Clin Invest. 1997 ; 94 : 5243-48.
  13. Seibert K, Zhang Y, Leahy K, Hauser S, Masferrer J, Perkins W, Lee L, Isakson P. Pharmacological and biochemical demonstration of the role of cyclooxygenase-2 in inflammation and pain. P Natl Acad Sci. 1994 ; 91 : 12013-7. https://doi.org/10.1073/pnas.91.25.12013
  14. Willoughby DA. Heberden Oration, 1974. Human arthritis applied to animal models. Towards a better therapy. Ann Rheum Dis. 1975 ; 34 : 471-8. https://doi.org/10.1136/ard.34.6.471
  15. McDaniel ML, Kwon G, Hill JR, Marshall CA, Corbett JA. Cytokines and nitric oxide in islet inflammation and diabetes. P Soc Exp Biol Med. 1996 ; 211 : 24-32. https://doi.org/10.3181/00379727-211-43950D
  16. Yun YG. Dongeuibangjeiwacheobanghaeseol, Seoul : Euiseongdang Publishing Co. 1998 : 554-61, 265-81.
  17. Shin MK. Clinical traditional herbalogy, Seoul : Younglimsa. 1997 : 172, 252, 678, 759.
  18. Doo HK. Dongeuishingeihak, Seoul : The Oriental Medicine Research Institute. 1993 : 1267-70.
  19. Association of Kyung Hee University korean medicine herbalogy. Systermatic considerations of herbology. 1988 : 108.
  20. Kim CM, Kim TH, Moon YH, Shin SW, Lee KS, Lee BK, Lee SY, Lee YS, Lee LJ, Lim KP. Hanyakbangjeihakjeongyuo, Seoul : Jungdam Publishing Co. 2011 : 114-50.
  21. Seo BI, Lee JH, Choi HY, Kwon DY, Bu YM. Hanyakbonchohak. 2nd ed. Younglimsa. 2006 : 166-540.
  22. Min HK. Endocrinology, Korea medical. 1999 : 980-2.
  23. Park YK. Longevity and life prevention in eastern medicine (translated), Seoul : Rebooks. 2009 : 199
  24. Ock ES. Bonchohak, Seoul : Shinkwang. 2004 : 91.
  25. Shin MK. New edition of Bangyakhappyeon. Seoul : Younglimsa. 2002 : 253-670.
  26. Kim CM, Shin MK, Ahn DK, Lee KS. (The)Encyclopedia of oriental herbal medicine, Seoul : Jungdam. 1999 : 193-332.
  27. Cho E, Kang JH, Lee H. Anti-inflammatory Effect of Akebiae Lignum Parmacopuncture at KI10 on LPS-induced Acute Nephritis in Rats. J Korean Acupuncture & Moxibustion Med Soc. 2012 : 41-52.
  28. Seo HS. The Experimental Study on Anti-inflammation and Anti-oxidation of Indigo Naturalis and Rehmanniae Radix. J Korean Oriental Med Ophthalmol Otolaryngol Dermatol. 2008 ; 21 : 104-10.
  29. Yoon TS, Cheon MS, Kim SJ, Lee AY, Moon BC, Chun JM, Choo BK, Kim HK. Evaluation of Solvent Extraction on the Anti-Inflammatory Efficacy of Glycyrrhiza uralensis. Korean J Medicinal Crop Sci. 2010 ; 18 : 28-33.
  30. Lee KH, Rhee KH. Anti-Inflammatory Effects of Glycyrrhiza glabra Linne Extract in a Dextran Sulfate Sodium-Induced Colitis Mouse Model. Korean J Food Nutr. 2010 ; 23 : 435-9.
  31. Lee JM, Seo BI, Park JH, Roh SS. Effects of water extracts from Phyllostachys Folium on hyperlipidemia and liver damage induced by alcohol. Kor J Herbology. 2011 ; 26 : 31-6.
  32. Song JS, Park SY, Choi JH, Kim JH. Effects of Phyllostachyos Folium (PF) on solid tumor in mice. J Korean Oriental Med Ophthalmol Otolaryngol Dermatol. 2009 ; 22 : 39-49.
  33. Fan YF. Experience of treatment of oral ulcer with Integrative Medicine. Modern Journal of Integrated Traditional Chinese and Western Medicine. 2006 ; 15 : 216.
  34. Lai HY, Xiong GQ, A brief account of recurrent oral ulcer with TCM treatment. Journal of Practical Traditional Chinese Internal Medicine. 2008 ; 22 : 72-3.
  35. Ji Y. The cause of oral ulcer is related to strong fire Qi, Jiankangbidu. 2005 ; 2 : 39.
  36. Iontcheva I, Amar S, Zawawi KH, Kantarci A, Van Dyke TE. Role for moesin in lipopolysaccharide stimulated signal transduction. Infect Immun. 2004 ; 72(4) : 2312-20. https://doi.org/10.1128/IAI.72.4.2312-2320.2004
  37. Willeaume V, Kruys V, Mijatovic T, Huez G. Tumor necrosis factor-alpha production induced by viruses and by lipopolysaccharides in macrophages: similarities and differences. J Inflamm. 1995-1996 ; 46(1) : 1-12.
  38. Funk CD, Frunk LB, Kennedy ME, Pong AS, Fitzgerald GA. Human platelet/erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression, and gene chromosomal assignment. FASEB J. 1991 ; 5(9) : 2304-12.
  39. Weisz A, Cicatiello L, Esumi H. Regulation of the mouse inducible-type nitric oxide synthase gene promoter by interferon-$\gamma$, bacterial lipopolysaccharide, and NG-monomethyl-L-arginine. Biochem J. 1999 ; 316 : 209-15.
  40. Caivano M. Role of MAP kinase cascades in inducing arginine transporters and nitric oxide synthetase in RAW 264.7 macrophages. FEBS Lett. 1999 ; 429(3) : 249-53.