Herbal Formula Science (대한한의학방제학회지)

The Korean Medicine Society for the Herbal Formula Study (대한한의학방제학회)
권호 표지
DOI QR코드

DOI QR Code

Evaluation of Efficacy evaluation of Hwangryunhaedok-tang and Gungangbuja-tang on lipopolysaccharide (LPS)-induced inflammation mouse model

Lipopolysaccharide로 유도된 염증 mouse model에서의 황련해독탕(黃連解毒湯)과 건강부자탕(乾薑附子湯)의 효능평가

  • Choi, You-Youn (Dept. of Prescriptionology, College of Oriental Medicine, Institute of Oriental Medicine, Kyung-Hee University) ;
  • Kim, Mi-Hye (Dept. of Prescriptionology, College of Oriental Medicine, Institute of Oriental Medicine, Kyung-Hee University) ;
  • Lee, Tae-Hee (Formulae Pharmacology Dept. School of Oriental Medicine, Ga-Chon University) ;
  • Yang, Woong-Mo (Dept. of Prescriptionology, College of Oriental Medicine, Institute of Oriental Medicine, Kyung-Hee University)
  • 최유연 (경희대학교 한의과대학 처방제형학교실) ;
  • 김미혜 (경희대학교 한의과대학 처방제형학교실) ;
  • 이태희 (가천대학교 한의과대학 방제학교실) ;
  • 양웅모 (경희대학교 한의과대학 처방제형학교실)
  • Received : 2012.11.17
  • Accepted : 2012.12.12
  • Published : 2012.12.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives : The aim of this study was to evaluate the efficacy of Hwangryunhaedok-tang (HHT) and Gungangbuja-tang (GBT) on lipopolysaccharide (LPS)-induced mouse model of inflammation. HHT and GBT are one of the representative prescriptions of cold drug and one of the representative prescriptions of hot drug, respectively. For experimental evaluation of their efficacy, we investigated the anti-inflammatory effects of HHT and GBT on LPS-induced inflammation and the mechanisms of their action. Methods : ICR mice were given a HHT (50, 500 mg/kg), GBT (100, 1000 mg/kg) extract orally on three consecutive days. On the third day, they were administered LPS intraperitoneally (35 mg/kg), 1 h after the last sample administration. Blood and liver samples were taken 6 h after the LPS challenge. Cytokine expression and inflammation-related protein factor analyses were performed by Western blotting. Results : Oral administration of HHT significantly reduced pro-inflammatory cytokines, including interleukin (IL)-6, and interferon (IFN)-${\gamma}$ in the serum. While GBT inhibited an increase of IL-6, IFN-${\gamma}$ was not affected. Immunoblot analysis showed that LPS-induced NF-${\kappa}b$ activation was inhibited by GBT, meanwhile HHT only inhibited NF-${\kappa}b$ expression at high does (500 mg/kg). In addition, HHT and GBT inhibited LPS-induced phosphorylation of Erk1/2, Jnk and p38 MAPKs. GBT also significantly inhibited i-Nos and Cox-2 expression, and HHT inhibited only i-Nos expression. Conclusions : Both of HHT and GBT showed anti-inflammatory effects against LPS-induced endotoxemia. However, HHT significantly decreased inflammatory cytokine levels, such as IL-6 and IFN-${\gamma}$ more than GBT, while GBT significantly inhibited inflammatory proteins, including NF-${\kappa}b$, MAP Kinases, i-Nos and Cox-2, more than HHT. These results suggest that HHT and GBT regulate the different mechanisms of action and pathways, presumably by regulating cytokine levels (IL-6, IFN-${\gamma}$), NF-${\kappa}b$ activation, and several pro-inflammatory gene expression, although both of HHT and GBT have anti-inflammatory effects.

본 연구를 통해서, 한(寒) 처방의 대표 처방인 황련해독탕(黃連解毒湯)과 열(熱) 처방의 대표 처방인 건강부자탕(乾薑附子湯) 모두 항염 효능을 확인할 수 있었으나, 그 작용 기전에 있어 뚜렷한 차이를 나타내었다. 이러한 차이는 한의학의 기본 이론인 한열에 대한 개념에 대한 연구의 초석이 될 수 있기를 바라며, 각 개별 약물의 효능 및 다른 처방들과 다른 기전적 실험이 추가적으로 필요할 것을 보인다.

Keywords

References

  1. 두호경, 박헌재. 황련해독탕의 약리학적 연구. 경희한의대논문집. 1982;5:103-14.
  2. Kang H, Bang TS, Lee JW, Lew JH, Eom SH, Lee K,Choi HY. Protective effect of the methanol extract from Cryptotaeniae japonica Hassk against lipopolysaccharide-induced inflammation in vitro and in vivo. BMC Complement Altern Med. 2012;12:199. https://doi.org/10.1186/1472-6882-12-S1-P199
  3. Feng YB, W. Q. Luo and S. Q. Zhu, "Explore new clinical application of Huang Lian and corresponding compound prescriptions from their traditional use," Zhongguo Zhong Yao ZaZhi. 2007;10:1221-5.
  4. Srivastava KC, Mustafa T. Ginger(Zingiberofficinale) and rheumatic disorders. Medical Hypotheses. 1989;29:25-8. https://doi.org/10.1016/0306-9877(89)90162-X
  5. Grzanna R, Lindmark L, Frondoza CG. Ginger an herbal medicinal product with broad antiinflammatory actions. Journal of Medicinal Food. 2005;8:125-32. https://doi.org/10.1089/jmf.2005.8.125
  6. Mascolo N, Jain R, Jain SC, Capasso F. Ethnopharmacologic investigation of ginger (Zingiberofficinale). Journal of ethnopharmacology. 1989;27:129-40. https://doi.org/10.1016/0378-8741(89)90085-8
  7. Sung YS, Choi HJ, Oh JM, Jee JG. The Effect of KKBT in Papain-Induced Osteoarthritis Mice Models. The Journal of Daejeon Oriental Medicine. 2012;21(1):33-52.
  8. 채인식. 傷寒論譯詮. 서울:高文社. 1991:334-5.
  9. Kim JH, Lee WC. A study on a paradigm of Radix Aconiti(附子) in the treatment of heart -systemic disease(心系疾患) through 'Sanghanron' (傷寒論). Journal of korean oriental internal medicine. 1999;20(1):9-32.
  10. Johnson, Latoya N. Koval, Michael. Cross-talk between pulmonary injury, oxidant stress, and gap junctional communication. Antioxidants & Redox Signaling. 2009;2:355-68.
  11. van Deuren M, Dofferhoff AS, van der Meer JW. Cytokines and the response to infection. The Journal of Pathology. 1992;168:349-56. https://doi.org/10.1002/path.1711680403
  12. Lin BR, Yu CJ, Chen WC, Lee HS, Chang HM, Lee YC, Chien CT, Chen CF. Green tea extract supplement reduces D-galactosamine-induced acute liver injury by inhibition of apoptotic and proinflammatory signaling. Journal of Biomedical Science. 2009;25:16-35.
  13. Mestre JR, Mackrell PJ, Rivadeneira DE, Stapleton PP, Tanabe T, Daly JM. Redundancy in the signaling pathways and promoter elements regulating cyclooxygenase-2 gene expression in endotoxin-treated macrophage/monocytic cells.Journal of Biological Chemistry. 2001;276:3977-82. https://doi.org/10.1074/jbc.M005077200
  14. Israf DA, Khaizurin TA, Syahida A, Lajis NH, Khozirah S. Cardamonin inhibits COXand iNOS expression via inhibition of p65 NF-${\kappa}b$ nuclear translocation and Ik-B phosphorylation in RAW264.7 macrophage cells. Molecular Immunology. 2007;44:673-9. https://doi.org/10.1016/j.molimm.2006.04.025
  15. Eduard, F.M., S.M.R. Martha, P.A. Victor and M. Pablo. Immunomodulatory effects of thalidomide analogs on LPSinduced plasma and hepatic cytokines in the rat. Biochemical pharmacology. 2004;68:1321-9. https://doi.org/10.1016/j.bcp.2004.06.018
  16. Harbrecht BG, Di Silvio M, Demetris AJ, Simmons RL, Billiar TR. Tumor necrosis factor-$\alpha$ regulates in vivo nitric oxide synthesis and induces liver injury during endotoxemia. Hepatology. 1994;20:1055-60. https://doi.org/10.1002/hep.1840200439
  17. Gill YG, Lee JH, Choi BT. The Serum and Immuno histochemical Analysis on the Anti-infammatory Effect of Aqueous Extract from Artemisia capillaris in the Liver of Lipopolysaccharide-injected Rat. Journal of life science. 2004;14:215-20. https://doi.org/10.5352/JLS.2004.14.2.215
  18. Israf DA, Khaizurin TA, Syahida A, Lajis NH, Khozirah S. Cardamonin inhibits COXand iNOS expression via inhibition of p65NF-jB nuclear translocation and Ij-Bphosphorylation in RAW264.7 macrophage cells. Mol Immunol. 2007;44:673-9. https://doi.org/10.1016/j.molimm.2006.04.025
  19. Israf DA, Khaizurin TA, Syahida A, Lajis NH, Khozirah S. Evidence for nucleotide receptor modulation of cross talk between MAP kinase and NF-kappa B signaling pathways in murine RAW264.7 macrophages. Am. J. Physiol. Cell Physiol. 286(4):C923-30.
  20. Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science. Science. 1995;24:1326-31.
  21. DeFranco AL, Hambleton J, McMahon M, Weinstein SL. Examination of the role of MAP kinase in the response of macrophages to lipopolysaccharide. Progress in clinical and biological research. 1995;392:407-20.
  22. Park HJ, Kim IT, Won JH, Jeong SH, Park EY, Nam JH, Choi J, Lee KT. Anti-inflammatory activities of ent-16alphaH,17-hydroxy-kauran-19-oic acid isolated from the roots of Siegesbeckia pubescens are due to the inhibition of iNOS and COX-2 expression in RAW 264.7 macrophages via NF-kappaB inactivation. European Journal of Pharmacology. 2007;558:185-93. https://doi.org/10.1016/j.ejphar.2006.11.036
  23. Qureshi AA, Tan X, Reis JC, Badr MZ, Papasian CJ, Morrison DC, Qureshi N.Suppression of nitric oxide induction and pro-inflammatory cytokines by novel proteasome inhibitors in various experimental models. Lipids in Health and Disease. 2011;10:177. https://doi.org/10.1186/1476-511X-10-177
  24. Lau FC, JosephJ A, McDonaldJ E. Attenuation of iNOS and COX2 by blueberry polyphenols is mediated through the suppression of NF-${\kappa}B$ activation. Journal of functional foods : the official journal of the International Society for Nutraceuticals & Functional Food. 2009;1:274-83.
  25. Jin M, Lee HJ, Ryu JH, Chung KS. Inhibition of LPS-induced NO production and NF-kappaB activation by a sesquiterpene from Saussurea lappa. Arch Pharm Res. 2000;2:54-8.
  26. Vodovotz Y, Prelich J, Lagoa C, Barclay D, Zamora R, Murase N, Gandhi CR. Augmenter of Liver Regeneration(ALR) is a Novel Biomarker of Hepatocellular Stress/Inflammation: In Vitro, In Vivo, and In Silico Studies. Journal of Molecular Medicine. 2012.