Differential Effect of Bovine Serum Albumin on Ginsenoside Metabolite-Induced Inhibition of ${\alpha}3{\beta}4$ Nicotinic Acetylcholine Receptor Expressed in Xenopus Oocytes

  • Lee, Jun-Ho (Research Laboratory for the Study of Ginseng Signal Transduction and Dept. of Physiology, College of Veterinary Medicine Konkuk University) ;
  • Jeong, Sang-Min (Research Laboratory for the Study of Ginseng Signal Transduction and Dept. of Physiology, College of Veterinary Medicine Konkuk University) ;
  • Lee, Byung-Hwan (Research Laboratory for the Study of Ginseng Signal Transduction and Dept. of Physiology, College of Veterinary Medicine Konkuk University) ;
  • Kim, Dong-Hyun (College of Pharmacy, KyungHee university) ;
  • Kim, Jong-Hoon (Research Laboratory for the Study of Ginseng Signal Transduction and Dept. of Physiology, College of Veterinary Medicine Konkuk University) ;
  • Kim, Jai-Il (Dept. of Life Science, Kwnangju Institute of Science and Technology) ;
  • Lee, Sang-Mok (Research Laboratory for the Study of Ginseng Signal Transduction and Dept. of Physiology, College of Veterinary Medicine Konkuk University) ;
  • Nah, Seung-Yeol (Research Laboratory for the Study of Ginseng Signal Transduction and Dept. of Physiology, College of Veterinary Medicine Konkuk University)
  • Published : 2003.10.01

Abstract

Ginsenosides, major active ingredients of Panax ginseng, that exhibit various pharmacological and physiological actions are transformed into compound K (CK) or M4 by intestinal microorganisms. CK is a metabolite derived from protopanaxadiol (PD) ginsenosides, whereas M4 is a metabolite derived from protopanaxatriol (PT) ginsenosides. Recent reports shows that ginsenosides might playa role as pro-drugs for these metabolites. In present study, we investigated the effect of bovine serum albumin (BSA), which is one of major binding proteins on various neurotransmitters, hormones, and other pharmacological agents, on ginsenoside $Rg_{2-}$, CK-, or M4-induced regulation of $\alpha3\beta4$ nicotinic acetylcholine (ACh) receptor channel activity expressed in Xenopus oocytes. In the absence of BSA, treatment of ACh elicited inward peak current ($I_{Ach}$) in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor. Co-treatment of ginsenoside $Rg_2$, CK, or M4 with ACh inhibited IAch in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor with reversible and dose-dependent manner. In the presence of 1% BSA, treatment of ACh still elicited $I_{Ach}$ in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor and co-treatment of ginsenoside $Rg_2$ or M4 but not CK with ACh inhibited $I_{Ach}$ in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor with reversible and dose-dependent manner. These results show that BSA interferes the action of CK rather than M4 on the inhibitory effect of $I_{Ach}$ in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor and further suggest that BSA exhibits a differential interaction on ginsenoside metabolites.

Keywords

References

  1. Abe, K., Cho, S. I., Kitagawa, I., Nishiyama, N., and Saito, H., Differential effects of ginsenoside $Rb_1$ and malonylginsenoside $Rb_2$ on long-term potentiation in the dentate gyrus of rat. Brain Res., 649, 7-11 (1994) https://doi.org/10.1016/0006-8993(94)91042-1
  2. Attele, A. S., Wu, J. A., and Yuan, C. S., Ginseng pharmacology: Multiple constituents and multiple actions. Biochem. Pharmacol., 58, 1685-1693 (1999) https://doi.org/10.1016/S0006-2952(99)00212-9
  3. Bojesen, I. N. and Bojesen, E., Binding of arachidonate and oleate to bovine serum albumin. J. Lipid Res., 35, 770-778 (1994)
  4. Bojesen, I. N. and Bojesen, E., Albumin binding of long-chain fatty acids: Thermodynamics and kinetics. J. Phys. Chem., 100, 17981-17985 (1996) https://doi.org/10.1021/jp962141m
  5. Choi, J. K., Ho, J., Curry, S., Qin, D. H., Bittman, R., and Hamilton, J. A., Interactions of very long-chain saturated fatty acids with serum albumin. J. Lipid Res., 43, 1000-1010 (2002a) https://doi.org/10.1194/jlr.M200041-JLR200
  6. Choi, S., Jung, S.Y., Kim, C.H., Kim, H.S., Rhim, H., Kim, S. C., and Nah, S. Y., Effect of ginsenosides on voltage-dependent $Ca^{2+}$ channel subtypes in bovine chromaffin cells. J. Ethnopharmacol., 74, 75-81 (2001) https://doi.org/10.1016/S0378-8741(00)00353-6
  7. Choi, S. Jung, S. Y., Lee, J. H., Sala, F., Criado, M., Mulet, J., Valor, L. M., Sala, S., Engel, A. G., and Nah, S. Y., Effects of ginsenosides, active components of ginseng, on nicotinic acetylcholine receptors expressed in Xenopus oocytes. Eur. J. Pharmacol., 442, 37-42 (2002b) https://doi.org/10.1016/S0014-2999(02)01508-X
  8. Choi, S., Lee, J. H., Oh, S., Rhim, H., Lee, S. M., and Nah, S. Y., Effects of ginsenoside $Rg_2$ on the 5-$HT_{3A}$ receptormediated ion current in Xenopus oocytes. Mol. Cells, 15, 108-113 (2003a)
  9. Choi, S. E., Choi, S., Lee, J. H., Whiting, P. J., Lee, S. M., and Nah, S. Y., Effects of ginsenosides on $GABA_A$ receptor channels expressed in Xenopus oocytes. Arch. Pharm. Res., 26, 28-33 (2003b) https://doi.org/10.1007/BF03179927
  10. Dascal, N., The use of Xenopus oocytes for the study of ion channels. CRC Critical Rev. Biochem., 22, 317-387 (1987) https://doi.org/10.3109/10409238709086960
  11. Habgood, M. D., Sedgwick, J. E. C., Dziegielewska, K. M., and Saunders, N. R., A developmentally regulated blood-cerebrospinal fluid transfer mechanism for albumin in immature rats. J. Physiol (Lond.)., 456, 181-192 (1992) https://doi.org/10.1113/jphysiol.1992.sp019332
  12. Hasegawa, H., J., Sung J. H., Matsumiya, S., and Uchiyama, M., Main ginseng saponin metabolites formed by intestinal bacteria. Planta Med., 62, 453-457 (1996) https://doi.org/10.1055/s-2006-957938
  13. Hasegawa, H., Suzuki, R., Nagaoka, T., Tezuka, Y., and Kadota, S. and Saiki, I., Prevention of growth and metastasis of murine melanoma through enhanced natural-killer cytotoxicity by fatty acid-conjugate of protopanaxatriol. Biol. Pharm. Bull., 25, 861-866 (2002) https://doi.org/10.1248/bpb.25.861
  14. Kanaoka, M., Akao, T., and Kobashi, K., Metabolism of ginseng saponins, ginsenosides by human intestinal flora. J. Trad. Med., 11, 241-245 (1994)
  15. Karikura, M., Miyase, T., Tanizawa, H., Taniyawa, T., and Takino, Y., Studies on absorption, distribution, excretion and metabolism of ginsenog saponins. VII. Comparison of the decomposition modes of ginsenoside $Rb_1$ and $Rb_2$ in the digestive tract of rats. Chem. Pharm. Bull., 39, 400-404 (1991) https://doi.org/10.1248/cpb.39.400
  16. Kim, C. K., Ahn, H. Y., Han, B. H., and Hong, S. K., Drugbiomacromolecule interaction V: Binding of ginsenosides to human and bovine serum albumins by fluorescence probe technique. Arch. Pharm. Res., 6, 63-68 (1983) https://doi.org/10.1007/BF02855703
  17. Kim, H. S., Lee, J. H., Goo, Y. S., and Nah, S. Y., Effects of ginsenosides on Ca channels and membrane capacitance in rat adrenal chromaffin cells. Brain Res. Bull., 46, 245-251 (1998) https://doi.org/10.1016/S0361-9230(98)00014-8
  18. Kim, S., Ahn, K., Oh, T. H., Nah, S. Y., and Rhim, H., Inhibitory effect of ginsenosides on NMDA receptor-mediated signals in rat hippocampal neurons, Biochem. Biophysical. Res. Comm., 296, 247-254 (2002) https://doi.org/10.1016/S0006-291X(02)00870-7
  19. Kudo. K., Tachikawa, E., Kashimoto, T., and Takahashi, E., Properties of ginseng saponin inhibition of catecholamine secretion in bovine chromaffin cells. Eur. J. Pharmacol., 341, 139-144 (1998) https://doi.org/10.1016/S0014-2999(97)01350-2
  20. Kullberg, R., Owens, J. L., Camacho, P., Mandel, G., and Brehm, P., Multiple conductance classes of mouse nicotinic acetylcholine receptors expressed in Xenopus oocytes, Proc. Natl. Acad. Sci., USA, 87, 2067-2071 (1990) https://doi.org/10.1073/pnas.87.6.2067
  21. Nah, S. Y. and McCleskey, E. W., Ginseng root extract inhibits calcium channels in rat sensory neurons through a similar path, but different receptor, as m-type opioids. J. Ethnopharmacol., 42, 45-51 (1994) https://doi.org/10.1016/0378-8741(94)90022-1
  22. Nah, S. Y., Park, H. J., and McCleskey, E. W., A trace component of ginseng that inhibits $Ca^{2+}$ channels through a pertussis toxin-sensitive G protein. Proc. Natl. Acad. Sci., USA, 92, 8739-8743 (1995) https://doi.org/10.1073/pnas.92.19.8739
  23. Noh, J. H., Choi, S., Lee, J. H., Betz, H., Kim, J. I., Park, C. S. Lee, S. M., and Nah, S. Y., Effects of ginsenosides on glycine receptor a1 channels expressed in Xenopus oocytes. Mol. Cells, 15, 34-39 (2003)
  24. Peters, T. Jr., All about Albumin Biochemistry, Genetics and Medical applications. San Diego: Academic Press, 256-260 (1996)
  25. Sala, F., Mulet, J., Choi, S., Jung, S. Y., Nah, S. Y., Rhim, H., Valor, L. M., Criado, M., and Sala, S., Effects of ginsenoside $Rg_2$ on human neuronal nicotinic acetylcholine receptors. J. Pharmacol. Exp. Ther., 301, 1052-1059 (2002) https://doi.org/10.1124/jpet.301.3.1052
  26. Sargent, P. B., The diversity of neuronal nicotinic acetylcholine receptors. Annu. Rev. Neurosci., 16, 403-443 (1993) https://doi.org/10.1146/annurev.ne.16.030193.002155
  27. Seong, Y. H., Shin, C. H., Kim, H. S., and Baba A., Inhibitory effect of ginseng total saponins on glutamate-induced swelling of cultured astrocytes. Biol. Pharm. Bull., 18, 1776-1778 (1995) https://doi.org/10.1248/bpb.18.1776
  28. Tachikawa, E., Kudo, K., Kashimoto, T., and Takashshi, E., Ginseng saponins reduce acetylcholine-evoked $Na^+$ influx and catecholamine secretion in bovine adrenal chromaffin cells. J. Pharm. Exp. Ther., 273, 629-636 (1995)
  29. Wakabayashi, C., Hasegawa, H., Murata, J., and Saiki, I., In vivo antimetastatic action of ginseng protopanaxadiol saponins is based on their intestinal bacterial metabolites after oral administration. Oncology Res., 9, 411-417 (1997)
  30. Wakabayashi, C., Murakami, K., Hasegawa, H., Murata, J., and Saiki, I., An intestinal bacterial metabolite of ginseng protopanaxadiol saponins has the ability to induce apoptosis in tumor cells. Biochem. Biophys. Res. Commun., 249, 725-730 (1998)