Journal of Natural Medicines

, Volume 65, Issue 2, pp 370–374 | Cite as

Antifibrotic activity of coumarins from Cnidium monnieri fruits in HSC-T6 hepatic stellate cells

  • Eunjin Shin
  • Chul Lee
  • Sang Hyun Sung
  • Young Choong Kim
  • Bang Yeon Hwang
  • Mi Kyeong LeeEmail author


The CHCl3 fraction of Cnidium monnieri fruits significantly inhibited the proliferation of hepatic stellate cells in an in-vitro assay system employing HSC-T6 hepatic stellate cell lines. Activity-guided fractionation of the CHCl3 fraction of C. monnieri led to the isolation of ten coumarins: osthol (1), meranzin (2), auraptenol (3), meranzin hydrate (4), 7-hydroxy-8-methoxy coumarin (5), imperatorin (6), xanthotoxol (7), xanthotoxin (8), bergapten (9) and isopimpinellin (10). Of these, compounds 1 and 6 significantly inhibited proliferation of HSCs in a time- and concentration-dependent manner. In addition, compounds 1 and 6 significantly reduced collagen content in HSC-T6 cells.


Cnidium monnieri Coumarin HSC-T6 Hepatic stellate cells Osthol Imperatorin 



We thank Prof. S.L. Freidman (Columbia University, New York) for the kindly gift of the HSC-T6 cells. This work was supported by the Medical Research Center Program (2010-0029480), the Regional Core Research Program (Chungbuk BIT Research-Oriented University Consortium) and Basic Science Research Program (2010-0025054) through the National Research Foundation of Korea (NRF).


  1. 1.
    Li D, Friedman SL (1999) Liver fibrogenesis and the role of hepatic stellate cells: new insights and prospects for therapy. J Gastroenterol Hepatol 14:618–633PubMedCrossRefGoogle Scholar
  2. 2.
    Tsukada S, Parsons CJ, Rippe RA (2006) Mechanisms of liver fibrosis. Clin Chim Acta 364:33–60PubMedCrossRefGoogle Scholar
  3. 3.
    Bataller R, Brenner DA (2005) Liver fibrosis. J Clin Invest 115:209–218PubMedGoogle Scholar
  4. 4.
    Wu J, Zern MA (2000) Hepatic stellate cells: a target for the treatment of liver fibrosis. J Gastroenterol 35:665–672PubMedCrossRefGoogle Scholar
  5. 5.
    Lee MK, Yang H, Yoon JS, Jeong EJ, Kim DY, Ha NR, Sung SH, Kim YC (2008) Antifibrotic activity of diterpenes from Biota orientalis leaves on hepatic stellate cells. Arch Pharm Res 31:866–871PubMedCrossRefGoogle Scholar
  6. 6.
    Uyama N, Shimahara Y, Okuyama H, Kawada N, Kamo S, Ikeda K, Yamaoka Y (2003) Carbenoxolone inhibits DNA synthesis and collagen gene expression in rat hepatic stellate cells in culture. J Hepatol 39:745–799CrossRefGoogle Scholar
  7. 7.
    Lee MK, Ha NR, Yang H, Sung SH, Kim GH, Kim YC (2008) Antiproliferative activity of triterpenoids from Eclipta prostrata on hepatic stellate cells. Phytomedicine 15:775–780PubMedCrossRefGoogle Scholar
  8. 8.
    Sakata R, Ueno T, Nakamura T, Sakamoto M, Torimura T, Sata M (2004) Green tea polyphenol epigallocatechin-3-gallate inhibits platelet-derived growth factor-induced proliferation of human hepatic stellate cell line LI90. J Hepatol 40:52–59PubMedCrossRefGoogle Scholar
  9. 9.
    Zhu YP (1999) Chinese material medica, chemistry, pharmacology and application. Harwood Academic Publishers, Amsterdam, pp 624–625Google Scholar
  10. 10.
    Zhang Q, Qin L, He W, Van Puyvelde L, Maes D, Adams A, Zheng H, De Kimpe N (2007) Coumarins from Cnidium monnieri and their antiosteoporotic activity. Planta Med 73:13–19PubMedCrossRefGoogle Scholar
  11. 11.
    Chou SY, Hsu CS, Wang KT, Wang MC, Wang CC (2007) Antitumor effects of osthol from Cnidium monnieri: an in vitro and in vivo study. Phytother Res 21:226–230PubMedCrossRefGoogle Scholar
  12. 12.
    Ito C, Furukawa H (1987) Constituents of Murraya exotica L. Structure elucidation of new coumarins. Chem Pharm Bull 35:4277–4285Google Scholar
  13. 13.
    Feger W, Brandauer H, Gabris P, Ziegler H (2006) Nonvolatiles of commercial lime and grapefruit oils separated by high-speed countercurrent chromatography. J Agric Food Chem 54:2242–2252PubMedCrossRefGoogle Scholar
  14. 14.
    Imai F, Kinoshita T, Sankawa U (1989) Constituents of the leaves of Murraya paniculata collected in Taiwan. Chem Pharm Bull 37:358–362Google Scholar
  15. 15.
    Kim JS, Kim JC, Shim SH, Lee EJ, Jin WY, Bae KH, Son KH, Kim HP, Sang SS, Chang HW (2006) Chemical constituents of the root of Dystaenia takeshimana and their anti-inflammatory activity. Arch Pharm Res 29:617–623PubMedCrossRefGoogle Scholar
  16. 16.
    Cai JN, Basnet P, Wang ZT, Komatsu K, Xu LS, Tani T (2000) Coumarins from the fruits of Cnidium monnieri. J Nat Prod 63:485–488PubMedCrossRefGoogle Scholar
  17. 17.
    Hitotsuyanagi Y, Kohima H, Ikuta H, Takeya K, Itokawa H (1996) Identification and structure–activity relationship studies of osthol, a cytotoxic principle from Cnidium monnieri. Bioorg Med Chem Lett 15:1791–1794CrossRefGoogle Scholar

Copyright information

© The Japanese Society of Pharmacognosy and Springer 2010

Authors and Affiliations

  • Eunjin Shin
    • 1
  • Chul Lee
    • 1
  • Sang Hyun Sung
    • 2
  • Young Choong Kim
    • 2
  • Bang Yeon Hwang
    • 1
  • Mi Kyeong Lee
    • 1
    Email author
  1. 1.College of PharmacyChungbuk National UniversityCheongjuKorea
  2. 2.College of Pharmacy and Research Institute of Pharmaceutical ScienceSeoul National UniversitySeoulKorea

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