Skip to main content

Protoberberine alkaloids and their reversal activity of P-gp expressed multidrug resistance (MDR) from the rhizome ofCoptis japonica Makino

Abstract

Six protoberberine alkaloids were isolated from the chloroform layer of the rhizome ofCoptis japonica Makino (Ranunculaceae). The structures of the isolated compounds were determined to be 6-([1,3]dioxolo[4,5-g]isoquinoline-5-carbonyl)-2,3-dimethoxy-benzoic acid methyl ester (1), oxyberberine (2), 8-oxo-epiberberine (3), 8-oxocoptisine (4), berberine (5) and palmatine (6) by physicochemical and spectroscopic methods. The compound3 (8-oxo-epiberberine) was first isolated from natural sources. The compounds were tested for cytotoxicity against five tumor cell linesin vitro by SRB method, and also tested for the MDR reversal activities. Compound4 was of significant P-gp MDR inhibition activity with ED50 value 0.018 μg/mL in MES-SA/DX5 cell and 0.0005 μg/mL in HCT15 cell, respectively.

This is a preview of subscription content, access via your institution.

References

  1. Cheng, H. Y. and Doskotch, R. W., Alkaloids of Thalictrum XXXI, Synthesis of Rugosinone.J. Nat. Prod., 43, 151–156 (1980).

    Article  CAS  Google Scholar 

  2. Cho, J. Y., Baik, K. U., Yoo, E. S., Yoshikawa, K., and Park, M. H.,In vitro antiinflammatory effects of woorenosides from the rhizomes ofCoptis japonica.J. Nat. Prod., 63, 1205–1209 (2000).

    PubMed  Article  CAS  Google Scholar 

  3. Choi, S. U., Kim, N. Y., Choi, E. J., Kim, K. H., and Lee, J. O., Establishment of doxorubicin-resistant subline derived from HCT15 human colorectal cancer cells.Arch. Pharm. Res., 19, 342–347 (1996).

    CAS  Article  Google Scholar 

  4. Elango, V. and Shamma, M., A pyrolytic route to the phthalide-isoquinolines.J. Org. Chem., 48, 4879–4881 (1983).

    Article  CAS  Google Scholar 

  5. Kim, M. S., Hwang, B. Y., Choe, S. G., Lee, M. K., Ro, J. S., and Lee, K. S., Alkaloidal components of Chelidonii Fructus.Kor. J. Pharmacogn., 31, 390–393 (2000).

    CAS  Google Scholar 

  6. Lee, H. Y. and Kim, C. W., Studies on the constituents ofBerberis amurensis Ruprecht.Kor. J. Pharmacogn., 28, 257–263 (1997).

    Google Scholar 

  7. Li, M., Chen, X., Tang, Q. M., and Zhang, J. S., Isoquinoline alkaloids fromThalictrum delavayi.Planta Med., 67, 189–190 (2001).

    PubMed  Article  CAS  Google Scholar 

  8. Mizuno, M., Kojima, H., Inuma, M., Yanaka, T., and Goto, K., Coumarin derivatives in Coptis Trifolia.Phytochemistry, 31, 717–719 (1992).

    Article  CAS  Google Scholar 

  9. Moriyasu, M., Ichimaru, M., Sawada, Y., Izutsu, K., Nishiyama, Y., and Kato, A., Analysis of alkaloids inNandina domestica by means of HPLC and TLC-densitometry.Shoyakugaku Zassi, 46, 143–149 (1992).

    CAS  Google Scholar 

  10. Otsuka, H., Fujimura, H., Sawada, T., and Goto, M., Studies on Anti-inflammatory Agent II. Anti-inflammatory constituents from Rhizome ofCoptis japonica MAKINO.Yakugakuzasshi, 101, 883–890 (1981).

    CAS  Google Scholar 

  11. Pinho, P. M. M., Pinto, M. M. M., Kijioa, A., Pharadai, K., Diaz, J., and Herz, W., Protoberberine alkaloids fromCoscinium fenestratum.Phytochemistry, 31, 1403–1407 (1992).

    Article  CAS  Google Scholar 

  12. Rahman, A. U., Ahmad, S., Bhatti, K., and Choudhary, M. I., Alkaloidal constitients ofFumaria indica.Phytochemistry, 40, 593–596 (1995).

    Article  Google Scholar 

  13. Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J., Vistica, D., Warren, J. T., Bokesch, H., Kenney, S., and Boyd, M. R., New colorimetric cytotoxicity assay for anticancer-drug screening.J. Natl. Cancer Inst., 82, 1107–1112 (1990).

    PubMed  Article  CAS  Google Scholar 

  14. Tang, W. and Eisenbrand, G.,Coptis supp. In: Chinese drugs of plant origin. Springer Verlag, New York, pp. 362–371 (1992).

    Google Scholar 

  15. Wu, W. N., Beal, J. L., and Doskotch, R. W., Alkaloids of Thalictrum XXX, eleven minor alkaloids fromThalictrum rugusum.J. Nat. Prod., 43, 143–150 (1980).

    Article  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Kang Ro Lee.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Min, Y.D., Yang, M.C., Lee, K.H. et al. Protoberberine alkaloids and their reversal activity of P-gp expressed multidrug resistance (MDR) from the rhizome ofCoptis japonica Makino. Arch Pharm Res 29, 757 (2006). https://doi.org/10.1007/BF02974076

Download citation

Key words

  • Coptis japonica
  • Ranunculaceae
  • Protoberberine alkaloid
  • 8-Oxo-epiberberine
  • Multidrug resistance