Abstract
(+)-Eudesmin [4,8-bis (3,4-dimethoxyphenyl)-3,7-dioxabicyclo[3.3.0]octane] was isolated from the stem bark ofMagnolia kobus DC. var.borealis Sarg. and found to have neuritogenic activity. 50 μM (+)-eudesmin induced neurite outgrowth and enhanced nerve growth factor (NGF)-mediated mediated neurite outgrowth from PC12 cells. At this concentration, (+)-eudesmin also enhanced NGF-induced neurite-bearing activity and this activity was partially blocked by various protein kinase inhibitors. These included PD98059, a mitogen-activated protein kinase (MAPK) kinase inhibitor. GF109203X, a protein kinase C (PKC) inhibitor and H89, a protein kinase A (PKA) inhibitor. These results suggest that (+)-eudesmin can induce neurite outgrowth from PC12 cells by stimulating up-stream MAPK, PKC and PKA pathways.
Similar content being viewed by others
References
Angus, W. G. R. and Contreras, M. L., Aroclor 1254 alters the binding of125I-labeled nerve growth factor in PC12 cells.Neurosci. Lett., 191, 23–26 (1995).
Ashcroft, M., Stephens, R. M., Hallberg, B., Downward, J., and Kaplan, D. R., The selective and inducible activation of endogenous PI3-kinase in PC12 cells results in efficient NGF-mediated survival but defective neurite outgrowth.Oncogene, 18, 4586–4597 (1999).
Connor, B. and Dragunow, M., The role of neuronal growth factors in neurodegenerative disorders of the human brain.Brain Res. Rev., 27, 1–39 (1998).
Doherty, P., Mann, D. A., and Walsh, F. S., Comparison of the effects of NGF, activators of protein kinase C, and a calcium inophore on the expression of Thy-1 and N-CAM in PC12 cell cultures.J. Cell Biol., 107, 333–340, (1988).
Fujita, Y., Kikuchi, M., and Fujita, I., Miscellaneous contributions to the essential oils of the plants from various territories. XXXV. Components of the essential oils ofMagnolia kobus DC. (1).Yakugaku Zasshi, 95, 235–237 (1975).
Greene, L. A. and Tischler, A. S., Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor.Proc. Nat. Acad. Sci. U.S.A., 73, 2424–2428 (1976).
Gysbers, J. W. and Rathbone, M. P., Guanosine enhances NGF-stimulated neurite outgrowth in PC12 cells.Neuro Report, 3, 997–1000 (1976).
Hirao, T., Tsuge, N., Imai, S., Shin-Ya, K., and Seto, H., Nerfilin, a novel microbial metabolite inducing neurite outgrowth of PC12 cells.J. Antibiotics, 48, 1494–1496 (1995).
Iida, T., Nakano, M., and Ito, K., Hydroperoxysesquiterpene and lignan constituents ofMagnolia kobus.Phytochem, 21, 673–675 (1982).
Kim, Y. G., Studies on the antimicrobial activities of the extractives from Magnolia (Magnolia kobus DC. var.borealis Sarg).Mokchae Konghak, 27, 105–114 (1999).
Leprince, P., Bonvoisin, C., Rogister, B., Mazy-Servais, C., and and, Moonen, G., Protein kinase- and staurosporinedependent induction of neurite outgrowth and plasminogen activator activity in PC12 cells.Biochem. Pharmacol, 52, 1399–1405 (1996).
Li, P., Matsunaga, K., Yamamoto, K., Yoshikawa, R., Kawashima, K., and Ohizumi, Y., Nardosinone, a novel enhancer of nerve growth factor in neurite outgrowth from PC12D cells.Neurosci. Lett., 273 53–56 (1999).
Mann, D. A., Doherty, P., and Walsh, F. S., Increased intracellular cyclic AMP differentially modulates nerve growth factor induction of three neuronal recognition molecules involved in neurite outgrowth.J. Neurochem, 53, 1581–1588 (1989).
Middlemiss, P. J., Glasky, A. J., Rathbone, M. P., Werstuik, E., Hindley, S., and Gysbers, J., AIT-082, a unique purine derivative, enhances nerve growth factor mediated neurite outgrowth from PC12 cells.Neurosci. Lett., 199, 131–134 (1995).
Obermeier, A., Bradshaw, R. A., Seedorf, K., Choidas, A., Schlessinger, J., and Ullrich, A., Neuronal differentiation signals are controlled by nerve growth factor receptor/Tx0 binding sites for SHC and PLC.EMBO J., 13, 1585–1590 (1994).
Pang, L., Sawada, T., Decker, S. J., and Saltiel, A. R., Inhibition of MAP kinase blocks the differentiation of PC-12 cells induced by nerve growth factor.J. Biol. Chem., 270, 13585–13588 (1995).
Patrick, Jr. C. W., Kukreti, S., and McIntire, L. V., Quantitative effects of peripheral monocytes and nerve growth factor on CNS neural morphometric outgrowth parameters in virtro.Exp. Neurol., 138, 277–285 (1996).
Pradines, A., Magazin, M., Schiltz, P., Le Fur, G., Caput, D., and Ferrara, P., Evidence for nerve growth factor-potentiating activities of the nonpeptidic compound SR 57746A in PC12 cells.J. Neurochem., 64, 1954–1964 (1995).
Sanchez, S., Jimenez, C., Carrera, A. C., Diaz-Nido, J., Avila, J., and Wandosell, F., A cAMP-activated pathway, including PKA and PI3K, regulated neuronal differentiation.Neurochem. Int., 44 231–242 (2004).
Sano, M. and Kitajima, S., Activation of mitogen-activated protein kinases is not required for the extension of neurites from PC12D cells triggered by nerve growth factor.Brain Res., 785, 299–308 (1998).
Tsuji, M., Inanami, O., and Kuwabara, M., Induction of neurite outgrowth in PC12 cells by-phenyl-N-tert-butylnitron through activation of protein kinase C and the Ras-extracellular signal-regulated kinase pathway.J. Biol. Chem., 276, 32779–32785 (2001).
Wood, K. W., Sarnecki, C., Roberts, T. M., and Blenis, J., Ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases: MAP kinase, Raf-1, and RSK.Cell, 68, 1041–1050 (1992).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yang, Y.J., Park, J.I., Lee, HJ. et al. Effects of (+)-eudesmin from the stem bark ofMagnolia kobus DC. var.borealis Sarg. on neurite outgrowth in PC12 cells. Arch Pharm Res 29, 1114–1118 (2006). https://doi.org/10.1007/BF02969301
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02969301