Inhibitory Effect of Curcumae Longae Radix on Fibrogenesis in Hepatic Stellate Cell Line, LX-2

울금(鬱金)이 간성상세포의 섬유화 억제에 미치는 영향

  • Kim, Se-Hoon (Dept. of Internal Medicine, College of Oriental Medicine, Kyung-hee University) ;
  • Woo, Hong-Jung (Dept. of Internal Medicine, College of Oriental Medicine, Kyung-hee University) ;
  • Kim, Young-Chul (Dept. of Internal Medicine, College of Oriental Medicine, Kyung-hee University) ;
  • Lee, Jang-Hoon (Dept. of Internal Medicine, College of Oriental Medicine, Kyung-hee University)
  • 김세훈 (경희대학교 한의과대학 간계내과학교실) ;
  • 우홍정 (경희대학교 한의과대학 간계내과학교실) ;
  • 김영철 (경희대학교 한의과대학 간계내과학교실) ;
  • 이장훈 (경희대학교 한의과대학 간계내과학교실)
  • Published : 2009.06.30

Abstract

Objectives : This study was performed to investigate the anti-fibrogenic effect of Curcumae Longae Radix on human hepatic stellate cells. Materials and Methods: Hepatic stellate cells (LX-2) were treated with various concentrations of Curcumae Longae Radix extract for 24, 48, and 72 hours. It was extracted with distilled water. After the treatment, cell viability, proliferation, cell cycle analysis, procollagen levels and the mRNA of the ASMA, TIMPl, TIMP2, MMP2, collagen type la, PDGF-receptor-beta and TGF-beta were measured by using MTT assay, BrdU assay, RT-PCR, and procollagen type 1 C-peptide EIA kit. Results : The viability of HSCs decreased in the 48 hours group, and proliferation of HSCs decreased as the concentration increased. In the cell cycle analysis, Curcumae Longae Radix decreased the ratio of M phase, and increased the ratio of apoptosis, G0/G1 and S phase. In the RT-PCR, the mRNA expression of the collagen type la and ASMA decreased with the Curcumae Longae Radix treatment. The production of procollagen by the HSCs was decreased by the treatment of Curcumae Longae Radix with high dose. Conclusion : These results suggest that Curcumae Longae Radix is helpful in the treatment of liver fibrosis as well as liver cirrhosis.

Keywords

References

  1. 통계청, 국민건강영양조사 2007.
  2. Kwan Sik Lee. Hepatic Fibrogenesis. Kor J Hepatology. 2005;11(2s):9-19.
  3. Friedman SL. Hepatic fibrosis-Overview. Toxicology 2008.
  4. Yoshiji H, Kuriyama S, Noguchi R, IkenakaY, Yoshii J, YanaseK, et al. Amelioration of liver fibrogenesis by dua linhibition of PDGF and TGF-beta with a combination of imatinib mesylate and ACE inhibitor in rats. Int J Mol Med. 2006;17(5):899-904
  5. Shimizu I, Kohno N, Tamaki K, Shono M, Huang HW, He JH, et al. Female hepatology: favorable role of estrogen in chronic liver disease with hepatitis B virus infection. World J Gastroenterol. 2007;13(32):4295-305.
  6. 최은경, 이장훈, 김영철, 우홍정. 단삼이 간성상 세포의 섬유화 억제에 미치는 영향. 대한한방내과학회지. 2008;29(2):299-310.
  7. 김성아, 우홍정, 김영철, 이장훈. 인진이 간성상 세포의 섬유화 억제에 미치는 영향. 대한한방내과학회지. 2008;29(1):177-88.
  8. Yumei Fu, Shizhong Zheng, Jianguo Lin, Jan Ryerse, Anping Chen. Curcumin protects the Rat Liver from CCl4-caused injury and Fibrogenesis by Attenuating Oxidative Stress and Suppressing Inflammation. Mol Pharmacol. 2008;73:399-409. https://doi.org/10.1124/mol.107.039818
  9. A Chen, S Zheng. Curcumin inhibits connective tissue growth factor gene expression in activated hepatic stellate cells in vitro by blocking NF-$_{K}B$ and ERK signaling. Br J Pharmacol. 2008 ;153(3):557-67. https://doi.org/10.1038/sj.bjp.0707542
  10. Wu SJ, Lin YH, Chu CC, Tsai YH, Chao JC. Curcumin or saikosaponin a improves hepatic antioxidant capacity and protects against CCl4-induced liver injury in rats. J Med Food. 2008;11(2):224-9. https://doi.org/10.1089/jmf.2007.555
  11. Yoysungnoen P, Wirachwong P, Changtam C, Suksamrarn A, Patumraj S. Anti-cancer and anti-angiogenic effects of curcumin and tetrahydrocurcumin on implanted hepatocellular carcinoma in nude mice. World J Gastroenterol. 2008;14(13): 2003-9. https://doi.org/10.3748/wjg.14.2003
  12. 식품의약품안전청. 대한약전외 한약규격집. 서울: 1985, p. 78.
  13. EM Jeong, SG Hwang, HH Park, JH Park, HT Kim, SW Oh et al. The Analysis of Mortality Rate According to CTP Score and MELD Score in Patients with Liver Cirrhosis. Kor J Hepatology. 2003;9(2):98-106. 2005;26(1) :1-11.
  14. Authur MJ. Reversibility of liver fibrosis and cirrhosis following treatmen forhepatitis C. Gastroenterology. 2002;122(5):1525-8. https://doi.org/10.1053/gast.2002.33367
  15. Issa R e al. Spontaneous recovery from micronodular cirrhosis: evidence for incomplete resolution with matrix cross-linking. Gastroenterology. 2004 ;126(7):1795-808. https://doi.org/10.1053/j.gastro.2004.03.009
  16. Lai CL, Chien RN, Leung NW, et al. A one-year trial fo lamivudine for chronic hepatitis B. N Engl J Med. 1998;339:61-8. https://doi.org/10.1056/NEJM199807093390201
  17. Davis G, Estevan-Mur R, Rustgi V, et al. Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. N Engl J Med. 1998;339 :1493-9. https://doi.org/10.1056/NEJM199811193392102
  18. Gong Y, Gluud C. Colchcine for pri Mar y biliary cirrhosis:a Cochrane Hepato-Biliary Group systematicreview ofrandomizedclinical trials. Am J Gastroenterol. 2005;100(8):1876-85. https://doi.org/10.1111/j.1572-0241.2005.41522.x
  19. Khan F, Peltekian KM, Peterson TC. effect of interferon-alpha, ribavirin, pentoxifylline, and interleukin-18 antibody on hepatitis C sera-stimulated hepatic stellate cell proliferation. J Interferon Cytokine Res. 2008;28(11):643-51. https://doi.org/10.1089/jir.2007.0123
  20. 김호철. 한약약리학. 집문당; 2001, p. 326-9.
  21. Reyes-Gordillo K, Segovia J, Shibayama M, Tsutsumi V, Vergara P, Moreno MG et al. Curcumin prevents and reverses cirrhosis induced by bile duct obstruction or$CCl_4$ in rats: role of TGF-beta modulation and oxidative stress. Fundam Clin Pharmacol. 2008;22(4) :417-27. https://doi.org/10.1111/j.1472-8206.2008.00611.x
  22. VerMa RJ, Mathuria N. Curcumin ameliorates aflatoxin-induced lipid peroxiation in liver and kidney of mice. Acta Pol Pharm. 2008;65(2) :195-202.
  23. Chen A, Zheng S. Curcumin inhibits connective tissue growth factor gene expression in activated hepatic stellate cells in vitro by blocking NF-kappaB and ERK signaling. Br J Pharmacol. 2008;153(3):557-67. https://doi.org/10.1038/sj.bjp.0707542
  24. Xu J, Fu Y, Chen A. Activation of Peroxisome proliferator-activated receptor gamma contributes to theinhibitory effects of curcumin on rat hepatic stellate cellgrowth. Am J Physiol Gastrointest. Liver Physiol 2003;285(1):G20-30.
  25. Cheng Y, PinJ, Xu LM. Effects of curcumin on Peroxisome proliferator-activated receptor gamma expression and nuclear translocation/ redistribution in culture-activated rathepatic stellatecells. Chin Med J (Engl). 2007;120(9) :794-801.