Characterization of Acetoxyscirpendiol of Paecilomyces tenuipes as Inhibitor of Sodium Glucose Co-transporters Expressed in Xenopus laevis Oocytes

  • Park, Il-Woon (Department of Life Sciences, University of Seoul) ;
  • Hwang, Gwi-Seo (College of Oriental Medicine Kyungwon University) ;
  • Kim, Ha-Won (Department of Life Sciences, University of Seoul) ;
  • Lee, Dong-Hee (Department of Life Sciences, University of Seoul)
  • Published : 2004.12.01


Cordyceps possesses numerous health-promoting ingredients including hypoglycemic agents. The mechanism for the reduction of circulatory sugar content, however, is still not fully understand. In this study, 4-beta acetoxyscirpendiol (ASD) was purified from the methanolic extracts from fruiting bodies of Paecilomyces tenuipes. Na+/Glucose transporter-1 (SGLT-1) was expressed in the Xenopus oocytes. The effect of ASD on the oocyte expressed SGLT-1 was analyzed utilizing the voltage clamp and 2-deoxy-D-glucose (2-DOG) uptake studies. ASD was shown to significantly inhibit SGLT-1 activity compared to the non-treated control in a dose- dependent manner. In the presense of its two derivatives (diacetoxyscirpenol or 15-acetoxyscirpendiol), SGLT-1 activity was greatly inhibited similarly as ASD. Between ASD derivatives, 15-acetoxyscirepenol showed inhibition equivalent to that of ASD while diacetoxyscirpenol did less degree of inhibition. Insummary , these results strongly indicate that ASD in P. tenuipes may serve as a functional substance in lowering blood sugar in the circulatory system. ASD and its derivatives can be utilized as inhibitors of SGLT-1.



  1. Doege, H., Bocianski, A., Joost, H.G., and Schurmann, A. (2000). Activity and genomic organization of human glucose transporter 9 (GLUT9), a novel member of the family of sugartransport facilitators predominantly expressed in brain and leukocytes. Biochem. J. 350, 771-776
  2. Due, A.D., Qu, Z.C., and Thomas, J.M. (1995). Role of the C-terminal tail of the SGLT-l glucose transporter in its expression and function in Xenopus laevis oocytes. Biochemistry 34, 5462-5471
  3. Jones, K (1997). Cordyceps, Tonic Food of Ancient China, Sylvan Press, Seattle, Washington, pp.52-61
  4. Juan, M.P., Dong, W., Beatriz, L., Hong, Y., Xia M., Ru, Y., and Darryl, C., (2004) GLUTI deficiency and other glucose transporter diseases. Eur. J. of Endocrin., 150, 627-633
  5. Kiho, T., Ookubo, K, Usui, S., Ukai, S., Hirano, K (1999) Structural features and hypoglycemic activity of a polysaccharide (CS-FlO) from the cultured mycelium of Cordyceps sinenesis. BioI. Pharm. Bull. 22, 966-970
  6. Kikuchi, H., Miyagawa, Y., Sahashi, Y., Inatomi, S., Haganuma, A., Nakahata, N., and Oshima, Y. (2004). Novel Spirocyclic Trichothecanes, Spirotenuipesine A and B, Isolated from Entomopathogenic Fungus, Paecilomyces tenuipes. J. Org. Chem.69(2), 352-356
  7. Kirwan, J. P., and del Aguila, L. F. (2003). Insulin signaling, exercise and cellular integrity. Biochem. Soc. Trans. 31, 1281-1285
  8. Konno, S., Tortorelis, D.G., Fullerton, S.A., Samadi, A.A., Hettiarachchi, J. and Tazaki, H. (2001) Possible hypoglycemic effect of Maitake mushroom on Type 2 diabetic patients. Diabetic Medicine, 18, 1010-1015
  9. Lee, D.H. and Kim H.W. (2004) Inhibition of GLUT-l expressed in Xenopus laevis Oocytes by acetoxyscirpendiol of p. tenuipes. J. of Applied Phamocology 12(2), 74-78
  10. Lee, D.H. (1998). Characterization of 27K zein as a transmembrane protein. J. Biochem. Mol. Biol. 31(2), 196-200
  11. Lee, D.H., Selester, B., and Pedersen, K. (1995). Free movement of 27K zein in the endoplasmic reticulum. Protein Eng. 9,91-96
  12. MandaI, A., Verri, T., MandaI, PK, Storelli, C., and Ahearn, GA (2003) Expression of Na(+) /D-glucose cotransport in Xenopus laevis oocytes by injection of poly(A)(+) RNA isolated from lobster (Homarus americanus) hepatopancreas. Comp Biochem Physiol A Mol Integr PhysioL 135(3),467-75
  13. Nam, K.S., Jo, Y.S., Kim, Y.H., Hyun, J.W., and Kim, H.W. (2001). Cytotoxic activities of acetoxyscirpenediol and ergosterol peroxide from Paecilomyces tenuipes. Life Sci. 69(2), 229-237
  14. Oulianova, N., Falk, S., and Berteloot, A .(200l) Two-step mechanism of phroridzin binding to the SGLTl protein in the kidney. J. Membrane BioI. 179,223-242
  15. Rudlowski C, Becker AJ, Schroder W, Rath W, Buttner R, and Moser M. (2003). GLUTl messenger RNA and protein induction relates to the malignant transformation of cervical cancer. Am J Clin PatholI 20(5), 691-698
  16. Rumsey, S. C., Daruwala, R., AI-Hasani, H., Zarnowski, M. J., Simpson, I. A., and Levine, M. (2003). Dehydroascorbic acid transport by GLUT4 in Xenopus oocytes and isolated rat adipocytes. J. Biol. Chem. 275, 28246-28253
  17. Talpur NA, Echard BW, Fan AY, Jaffari O, Bagchi D., and Preuss HG (2002) Antihypertensive and metabolic effects of whole Mitake mushroom powder and its fractions in two rat strains. Mol Cell Biochem. 237, 129-136
  18. Wood, I.S., and Trayhurn P. (2003) Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br. 1. Nutr. 89(1), 3-9