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Article

Panaxadiol Glycosides that Induce Neuronal Differentiation in Neurosphere Stem Cells

Supporting Info

Jia Wei Liu,^† Song Jiu Tian,^‡ Jean de Barry,^§ and Bang Luu*^†

Laboratoire de Chimie Organique des Substances Naturelles, UMR 7177 CNRS-Universit Louis Pasteur, 5 Rue Blaise Pascal, F-67084 Strasbourg, France, National Research Center for the Standardization of Pharmaceutical and Biological Products, Temple of Heaven, 100050 Beijing, People's Republic of China, and Institut des Neurosciences Cellulaires et Intgratives, Centre de Neurochimie, UMR 7168 CNRS-Universit Louis Pasteur, 5 Rue Blaise Pascal, F-67084 Strasbourg, France

J. Nat. Prod., 2007, 70 (8), pp 1329–1334

DOI: 10.1021/np070135j

Publication Date (Web): July 31, 2007

†

Laboratoire de Chimie Organique, Université Louis Pasteur.

‡

National Research Center.

Institut des Neurosciences, Université Louis Pasteur.

To whom correspondence should be addressed. Tel: +33-3-88411672. Fax: +33-3-88607464. E-mail: luu@chimie.u-strasbg.fr.

Abstract

Bioassay-guided fractionation, combined with screening based on EGF-responsive neural stem cells (NSCs) differentiation assay, has been used to search for active molecules from Panax notoginseng. Ginsenosides Rg3 (1), Rk1 (2), and Rg5 (3) were identified as potential neurogenic molecules. The degrees of their neurogenic effects were found to be 3 > 2 > 1. The neurogenic effect of 3 represents a biphasic dose- and time-dependent regulation. Transient exposure of NSCs to 8 μM 3 for 24 h followed by 1 μM and 72 h incubation was the optimal procedure for the induction of neurons in NSCs, and compound 3 resulted in an approximately 3-fold increase in neurogenesis at the expense of astrogliogenesis. The neurogenic effect of 3 was completely eliminated by the Ca²⁺ channel antagonist nifedipine. These findings imply that 3 may be utilized as a pharmacological agent in studying the molecular regulation of neurogenesis of brain stem cells and, subsequently, for treatment of neurodegenerative diseases.