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The anti-inflammatory effect of Lithospermum Erythrorhizon on lipopolysaccharide - induced inflammatory response in RAW 264.7 cells

LPS로 유도한 RAW 264.7 세포의 염증반응에서 자초(紫草)의 항염증 효과

  • Choi, Sun-Bok (Dept. of Herbology, College of Oriental Medicine, Wonkwang University) ;
  • Bae, Gi-Sang (Hanbang Body-fluid Research Center, Wonkwang University) ;
  • Jo, Il-Joo (Dept. of Herbal Resources, Professional Graduate School of Oriental Medicine Wonkwang University) ;
  • Park, Kyoung-Chel (Dept. of Herbology, College of Oriental Medicine, Wonkwang University) ;
  • Seo, Seung-Hee (Dept. of Herbal Resources, Professional Graduate School of Oriental Medicine Wonkwang University) ;
  • Kim, Dong-Goo (Dept. of Herbal Resources, Professional Graduate School of Oriental Medicine Wonkwang University) ;
  • Shin, Joon-Yeon (Dept. of Herbal Resources, Professional Graduate School of Oriental Medicine Wonkwang University) ;
  • Gwak, Tae-Sin (Dept. of Herbology, College of Oriental Medicine, Wonkwang University) ;
  • Lee, Jung-Hyun (Dept. of Herbology, College of Oriental Medicine, Wonkwang University) ;
  • Lee, Guem-San (Dept. of Herbology, College of Oriental Medicine, Wonkwang University) ;
  • Park, Sung-Joo (Dept. of Herbology, College of Oriental Medicine, Wonkwang University) ;
  • Song, Ho-Joon (Dept. of Herbology, College of Oriental Medicine, Wonkwang University)
  • 최선복 (원광대학교 한의과대학 본초학교실) ;
  • 배기상 (원광대학교 한방체액조절연구센터) ;
  • 조일주 (원광대학교 한약자원전문대학원) ;
  • 박경철 (원광대학교 한의과대학 본초학교실) ;
  • 서승희 (원광대학교 한약자원전문대학원) ;
  • 김동구 (원광대학교 한약자원전문대학원) ;
  • 신준연 (원광대학교 한약자원전문대학원) ;
  • 곽태신 (원광대학교 한의과대학 본초학교실) ;
  • 이정현 (원광대학교 한의과대학 본초학교실) ;
  • 이금산 (원광대학교 한의과대학 본초학교실) ;
  • 박성주 (원광대학교 한의과대학 본초학교실) ;
  • 송호준 (원광대학교 한의과대학 본초학교실)
  • Received : 2013.02.15
  • Accepted : 2013.03.21
  • Published : 2013.03.30

Abstract

Objective : Lithospermum Erythrorhizon (LE) has been used as an anti-bacterial and anti-inflammatory agent. However, it is unclear that LE aqueous extract could show the anti-inflammatory effects in RAW 264.7cells. The purpose of this study was to investigate the anti-inflammatory effect of aqueous extract from LE on lipopolysaccharide (LPS) - induced inflammatory response. Methods : To measure out the cytotoxicity of LE, we performed the MTT assay. To evaluate the anti-inflammatory effects of LE, we examined the inflammatory mediators such as nitric oxide (NO), prostaglandin E2 ($PGE_2$) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-${\alpha}$, interleukin, (IL)-$1{\beta}$ and (IL)-6) on RAW 264.7 cells. We also examined molecular mechanisms such as mitogen-activated protein kinases (MAPKs) and nuclear factor-B (NF-${\kappa}B$) activation by western blot. Results : Aqueous Extract from LE itself did not have any cytotoxic effect in RAW 264.7 cells. Aqueous extract from LE inhibited LPS-induced productions of inflammatory mediators such as NO, $PGE_2$, and pro-inflammatory cytokines including TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 in RAW 264.7cells. In addition, LE inhibited the phosphorylation of p38 kinases (p38), c-Jun $NH_2$-terminal kinase (JNK), and NF-${\kappa}B$ activation in RAW 264.7 cells. Conclusion : LE down-regulated LPS-induced production of inflammatory mediators through the inhibition of p38, JNK and NF-${\kappa}B$ activation. Taken together, these results could provide the evidence for the anti-inflammatory effects of LE. Therefore, LE may be a novel target in the management of inflammation and help to support a potential strategy for prevention and therapy of inflammatory diseases.

Keywords

References

  1. Behrens, EM. Macrophage activation syndrome in rheumatic disease: What is the role of the antigen presenting cell? Autoimmunity Reviews. 2008 : 305-8.
  2. Lopez-Bojorquez LN, Dehesa AZ, Reyes-Teran G. Molecular mechanisms involved in the pathogenesis of septic shock. Arch Med Res. 2004 ; 35 : 465–79. https://doi.org/10.1016/j.arcmed.2004.07.006
  3. McDaniel ML, Kwon G, Hill JR, Marshall CA, Corbett JA. Cytokines and nitric oxide in islet inflammation and diabetes. Proc Soc Exp Biol Med. 1996;211 : 32-24.
  4. Kim DH, Park SJ, Jung JY, Kim SC, Byun SH. Antiinflammatory effects of the aqueous extract of Hwangnyenhaedok-tang in LPS-activated macrophage cells. Kor J Herbol. 2009;24 : 47-39.
  5. Moncada S, Higgs EA. Endogenous nitric oxide: physiology pathology and clinical relevance. Eur J Clin Ivest. 1991;21 : 361-74. https://doi.org/10.1111/j.1365-2362.1991.tb01383.x
  6. Rocca, B, FitzGerald, GA. Cyclooxygenases and prostaglandins: shaping up the immune response. Int Immunopharmacol. 2002 ; 2 : 603-30. https://doi.org/10.1016/S1567-5769(01)00204-1
  7. Athman R, Philpott D. Innate immunity via Toll-like receptors and Nod proteins. Curr Opin Microbiol. 2004 ; 7 : 25-32. https://doi.org/10.1016/j.mib.2003.12.013
  8. Beinke S, Ley SC. Functions of NF-kappaB1 and NF-kappaB2 in immune cell biology. Biochem J. 2004 ; 382 : 393-409. https://doi.org/10.1042/BJ20040544
  9. Cho MH, Park YS, Hahn TR. Propionylshikonin from the roots of Lithospermum erythrorhizon cultivated in Korea. J Agric Food Chem. 1999 ; 47 : 4117-20. https://doi.org/10.1021/jf9902853
  10. Shin MK. Clinical Traditional Herbalogy. seoul : yonglin publisher. 2010 : 402-3.
  11. Ju JH, Cho HH, Lee YS. Progress on Phytochemical and Atopic Dermatitis related Study of the Root of Lithospermum erythrorhizon. Korean J Pharmacogn. 2010 ; 41(2) : 73-88.
  12. Kim YR, Cho SY, Seo DB, Kim SH, Lee SJ, Cho YH. Effects of Oral Intake of Gromwell Water Fraction on Ceramides Content and the Development of Atopic Dermatitis in NC/Nga Mice. korean j. food sci. technol. 2009 ; 41(5) : 547-51.
  13. Kim SH, Lee JY, Kim DK. Effects of Mori Folium, Arctii Fructus, Lithospermum Erythrorhizon on the Anti-allergic Response. J Kyung Hee Univ Med Cent. 2005 ; 21(1) : 71-9.
  14. Lee HH, Yoon JS, Song SY. Protective Effect of Lithospermum erythrorhizon oh Galactosamine Induced Liver Injury. Korean J. Microscopy. 2010 ; 40(1) : 29-35.
  15. Chinese Treditional medicine management agency . commission. 1th edition vol 6. shanghai:Chinese Treditional medicine management agency commission. 1999:525-31.
  16. Gao XM. Chinese traditional medicine. 1st rev. ed. beijing : China Press of Traditional Chinese Medicine. 2002 : 171-2.
  17. Seetharaman R, Park DJ, Park C, Park SJ, Park YH, Kim ST, Choi YH, Choi YW. In vitro and in vivo anticancer effects of Lithospermum erythrorhizon extract on B16F10 murine melanoma. J Ethnopharmacol. 2012 ; 144 : 335–45. https://doi.org/10.1016/j.jep.2012.09.017
  18. Lee JH, Jung KM, Bae IH, Cho SY, Seo DB, Lee SJ, Park YH, Lim KM. Anti - inflammatory and barrier protecting effect of Lithospermum erythrorhizon extracts in chronic oxazolone-induced murine atopic dermatitis. JDS. 2009 ; 56 : 58–73. https://doi.org/10.1016/j.jdermsci.2009.06.018
  19. Han KY, Kwon TH, Lee TH, Lee SJ, Kim SH, Kim JY. Suppressive effects of Lithospermum erythrorhizon extracts on lipopolysacchride-induced activation of AP-1 and NF-${\kappa}B$ via mitogen-activated protein kinase pathways in mouse macrophage cells. BMB reports. 2008 : 328-33. https://doi.org/10.5483/BMBRep.2008.41.4.328
  20. Ajizian SJ, English BK, Meals EA. Specific inhibitors of p38 and extracellular signal regulated kinase mitogen-activated protein kinase pathways block inducible nitric oxide synthase and tumor necrosis factor accumulation in murine macrophages stimulated with lipopolysaccharide and interferon-gamma. J Infect Dis. 1999 ; 179 : 939-44. https://doi.org/10.1086/314659
  21. Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev. 1991 ; 43 : 109-42.
  22. MaCartney-Francis N, Allen JB, Mizel DE, Albina JI, Xie QW, Nathan CF, Wahl SM. Suppression of arthritis by an inhibitor of nitric oxide synthase. J Exp Med. 1993 ; 178 : 749-54. https://doi.org/10.1084/jem.178.2.749
  23. Bishop-Bailey D, Calatayud S, Warner TD, Hla T, Michell A. Prostaglandins and the regulation of tumor growth. J Environ Pathol Tox Oncol. 2002 ; 21 : 93-101.
  24. Oh CH translation. simple immunology. 3nd rev. ed. seoul : Medical korea. 2006 : 161-200.
  25. Cobb MH, Goldsmith EJ. Dimerization in MAP-kinase signaling. Trends Biochem Sci. 2000 ; 25 : 7-9. https://doi.org/10.1016/S0968-0004(99)01508-X
  26. Celec P. Nuclear factor kappa B-molecular biomedicine the nest generation. Biomed Pharmacother. 2004 ; 58 : 365-71. https://doi.org/10.1016/j.biopha.2003.12.015
  27. Gang A, Aggarwal BB. Nuclear transcription factor-kappaB as a target for cancer drug development. Leukemia. 2002 ; 16(6) : 1053-68. https://doi.org/10.1038/sj.leu.2402482