Adipocyte Differentiation Inhibitor Isolated from the Barks of Phellodendron amurense

황백(Phellodendri Cortex)으로부터 분리한 지방세포 분화 저해물질

  • Published : 2003.06.01

Abstract

For the development of the anti-obesity natural drug, the inhibitor of adipocyte differentiation was screened from Korean traditional medicinal plants. Phellodendri Cortex was selected as a candidate of adipocyte differentiation inhibitor. An inhibitory compound PC-4 was purified from the methanol (MeOH) extract of Phellodendri Cortex using silica gel and ODS RP-18 column chromatography and HPLC. PC-4 was obtained as yellow powder; UV ${\lambda}_{max}$ (MeOH): 230, 260, 340 and 430 nm. The chemical structure of PC-4 was determined as an isoquionoline alkaloid, berberine, on the basis of various NMR experiments including $^1H-\;and\;^{13}C-NMR$. The PC-4 inhibited the differentiation of preadipocyte NIH-3T3 L1 cells at a concentration of $1\;{\mu}g/mL$.

Keywords

Phellodendri Cortex;inhibitor;adipocyte differentiation;Phellodendron amurense;berberine

References

  1. Michell, A.L. Becoming fat. Genes Develop. 16: 1-5 (2002) https://doi.org/10.1101/gad.964002
  2. Kim, J.P., Jung, M.Y., Kim, J.P. and Kim, S.Y. Antiphotooxidative activity of protoberberines derived from Coptis japonica Makino in the chlorophyll-sensitized photooxidation of oil. J. Agric. Food Chem. 48: 1058-1063 (2000) https://doi.org/10.1021/jf9909297
  3. Iwasa, K., Moriyasu, M., Yamori, T., Turuo, T., Lee, D.U. and Wolfgang, W. In vitro cytotoxicity of the protoberberine-type alkaloids. J. Nat. Prod. 64: 896-898 (2001) https://doi.org/10.1021/np000554f
  4. Park, K.S., Kang, K.C., Kim, J.H., Adams, D.J., lohng, T.N. and Paik, Y.K. Differentiation inhibitory effects of protoberberines on sterol chitin biosyntheses in Candida albicans. British J. Antimicrob. Chemother. 43: 667-674 (1999) https://doi.org/10.1093/jac/43.5.667
  5. Sabir, M. and Bhide, N.K. Study of some pharmacological actions of berberine. Indian J. Physiol. Pharmacol. 15: 111-132 (1971)
  6. Kim, Y.S. Transcriptional factors involved in insulin resistance. Korean J. Lipidol. 9: 28-35 (1999)
  7. Mitani, N., Murakami, K., Yamaura, T., Ikeda, T. and Saiki, I. Inhibitory effect of berberine on the mediastinal lymph node metastasis produced by orthotopic implantation of Lewis lung carcinoma. Cancer Lett. 165: 35-42 (2001) https://doi.org/10.1016/S0304-3835(00)00710-2
  8. Kim, J.B. New horizon in atherosclerosis research: Insights into fat cell differentiation and insulin sensitivity with ADDl/SREBPl and PPAR$\gamma$. Korean J. Lipidol. 11: 79-83 (2001)
  9. Loftus, T.M. and Lane, M.D. Modulating the transcriptional control of adipogenesis. Genetics Develop. 7: 603-606 (1997)
  10. Huang, K.C. The Pharmacology of Chinese Herbs, p. 289. CRC press, Tokyo, Japan (1993)
  11. Robert, M.C., Robert, E.L. and Robert, E.M. Jr. Molecular regulation of adipocyte differentiation. Cell Develop. BioI. 10: 3-10 (1999) https://doi.org/10.1006/scdb.1998.0276
  12. Jiang, M.S and Lane, M.D. Sequential repression and activation of the CCAAT enchancer-binding protein-$\alpha$ (C/EBP$\alpha$) gene during adipogensis. Proc. Natl. Acad. Sci. USA 97: 12519-12523 (2000) https://doi.org/10.1073/pnas.220426097
  13. Szeto, S., Yow, C.M.N. and Fung, K.W. Characterization of berberine on human cancer cells in culture. Turk. J. Med. Sci. 32: 363-368 (2002)
  14. Jeon, Y.W., Jung, J.W.., Kang, M.R., Chung, I.K. and Lee, W.T NMR studies on antitumor drug candidates, berberine and berberrubine. Bull. Korean Chem. Soc. 23: 391-394 (2002) https://doi.org/10.5012/bkcs.2002.23.3.391
  15. Holst, D. and Grimaldi, P.A. New factors in the regulation of adipose differentiation and metabolism. Lipidology 13: 241-245 (2002)
  16. Ren$e'$, K., Gert, S. and Hesselink, M.K.C. Optimization of Oil red O staining permits combination with immunofluorescence and automated quantification of lipids. Histochem. Cell. Biol. 116: 63-68 (2001)
  17. Uchiyama, T., Kamikawa, H. and Ogita, Z. Anti-ulcer effect of extract from Phellodendri cortex. Yakugaku Zasshi 109: 672-676 (1989)
  18. Evan, D.R., Christopher, J.W., Pere, P. and Bruce, M.S. Transcriptional regulation of adipogenesis. Genes Develop. 14: 1293-1307 (2000)
  19. Michio, S., Moritake, H., Zhou, Y.T., Wang, M.Y., Christopher, B.N. and Roger, H.U. Lipoapoptosis in beta-cells of obese prediabetic fa/fa rats. J. BioI. Chem. 273: 32487-32490 (1998) https://doi.org/10.1074/jbc.273.49.32487
  20. Bradford, B.L. and Bruce, M.S. Towards a molecular understanding of adaptive thermogenesis. Nature 404: 652-660 (2000)
  21. Rosen, E.D., Hsu, C.H., Wang, X., Sakai, S., Freeman, M.W., Gonzalez, F.J. and Spiegelman, B.M. C/EBP$\alpha$ induces adipogenesis through PPAR$\gamma$: a unified pathway. Genes Develop. 16: 22-26 (2002) https://doi.org/10.1101/gad.948702
  22. Pan, J.F., Yu, C., Zhu, D.Y., Zhang, H., Zeng, J.F., Jiang, S.H. and Ren, J.Y. Identification of three sulfate-conjugated metabolites of berberine chloride in healthy volunteers' urine after oral administration. Acta Pharmacol. Sin. 23: 77-82 (2002)
  23. Tang, Q.Q. and Lane, M.D. Role of C/EBP homologous protein (CHOP-10) in the programmed activation of CCAAT/enhancerbinding protein-$\beta$ during adipogensis. Proc. Natl. Acad. Sci. USA 97: 12446-12450 (2000) https://doi.org/10.1073/pnas.220425597
  24. Andrea, B., Laura, G. and Alexander, S. Rapamycin inhibits human adipocyte differentiation in primary culture. Obesity Res. 8: 249-254 (2000)
  25. Ramirez-Zacarias, J.L., Castro-Muiiozledo, F. and Kuri-Harcuch, W. Quantiation of adipose conversion and triglycerides by staining intracytoplasmic lipids with Oil red O. Histochemistry 493-497 (1992)
  26. Tracy, C.L. Purification and crystallization of rat liver fatty acid synthetase. Arch. Biochem. Biophys. 209: 613-619 (1981) https://doi.org/10.1016/0003-9861(81)90320-9
  27. Xueming, G. and Kan, L. Analysis of gene expression profile during 3T3-L1 preadipocyte differentiation. Gene 251: 45-53 (2000) https://doi.org/10.1016/S0378-1119(00)00192-X
  28. Spiegelman, B.A. and Flier, J.S. Adipogenesis and obesity: Rounding out the big picture. Cell 87: 377-389 (1996) https://doi.org/10.1016/S0092-8674(00)81359-8
  29. Chen, D. and Garg A. Monogenic disorders of obesity and body fat distribution. J. Lipid Res. 40: 1735-1746 (1999)
  30. Dils, R. and Carey, E. M. Methods in Enzymol. 35: 74-83 (1975) https://doi.org/10.1016/0076-6879(75)35140-9