Investigation of nerve growth factor promotor from fungi

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Novel cyathane-type diterpenoids, scabronine A-F, were isolated from the fruit body of the mushroom, Sarcodon scabrosus (Fr.) Karst. The stereostructures of those were elucidated on the basis of the spectroscopic analysis. Among these compounds, scabronines A, B, C and E exhibit inductive activity of the verve growth factor synthesis. Further investigation yielded three more congeners, scabronine G, H and I.When rat pheochromocytoma cells (PC-12) were cultivated with the conditioned medium of human astrocytoma cells (1321Nl) incubated with the new diterpenoids, scabronines A and G, isolated from Sarcodon scabrosus, they changed their morphology and there was neurite outgrowth. The scabronines increased the expression of nIRNA for nerve growth factor (NGF), and the secretion of NGF from 1321Nl cells in a concentration-dependent manner. However, the enhanced neurite outgrowth produced by the conditioned media was slightly inhibited by NGF neutralizing antibody, and the concentration of NGF released in response to the scabronines was insufficient to cause differentiation.In conclusion, the new diterpenoids scabronines A and G potently stimulate the secretion of neurotrophic factors, including NGF.They are useful drugs to clarify the mechanism of synthesis and secretion of neurotrophic factors.