New physiological function of secoiridoids: neuritogenic activity in PC12h cells

Previously, we have reported that geniposide isolated from an extract of Gardenia fructus has neuritogenic activity in PC12h cells, a subclone of rat pheochromocytoma cells. Furthermore, we have indicated that several geniposide-related iridoid compounds also had similar potent neuritogenic activity. In this study, we have examined the effects of various secoiridoid compounds [K-1, sweroside; K-2, swertiamarin; K-3, gentiopicroside; K-4, 6'-O-β-D: -glucopyranosylsweroside; K-5, 6'-O-β-D: -glucopyranosylgentiopicroside; K-6, 6'-O-β-D: -glucopyranosylswertiamarin; K-7, 5'-O-β-D: -glucopyranosylamarogentin; K-8, 5'-O-β-D: -glucopyranosylamaroswertin; H-1, n-butyl vogeloside; H-2, n-butyl epivogeloside; H-3, (7S)-secologanin butyl methyl acetal; H-4, (7R)-secologanin butyl methyl acetal; H-5, secologanin dimethyl acetal] isolated from various medicinal herbs. The secoiridoids H-1, H-2, H-3, H-4, and H-5 induced significant neurite outgrowth. Among these H-series compounds, H-2 was the most potent neuritogenic compound. Among the K-series compounds, K-1, K-2, K-3, and K-8 showed the most potent activity. These results suggest that secoiridoids have neuritogenic activity in PC12h cells and that these secoiridoid compounds are promising starting compounds for the development of neurotrophic factor-like and iridoid compounds.