Neuritogenic effect of natural iridoid compounds on PC12h cells and its possible relation to signaling protein kinases.

We examined effect of iridoid glucosides, aucubin, catalpol, geniposide and gardenoside, and their enzymic hydrolysates on neurite outgrowth of PC12h cells. Except for aucubin, these glucosides induced neurite outgrowth at 0.1 microgram/ml and above in medium after 3 d of treatment. Hydrolysates of the four glucosides all caused neuritogenesis. Geniposide hydrolysate enhanced responses of cells to carbachol and KCl-induced depolarization in terms of cytoplasmic free-calcium concentration. The aglucone of geniposide, genipin, also promoted neurite outgrowth in a dose-dependent manner (ED50 = 0.7 microM). The neuritogenic effect of genipin was partially or considerably inhibited in the presence of H-89 and genistein. All the results presented suggest that certain iridoid compounds can induce neuronal differentiation in PC12h cells through activation of components of the intracellular signal transduction pathway.