Investigation of nerve growth factor promotor from fungi

从蘑菇Sarcodon scabrosus (Fr.) Karst的子实体中分离到一种新型的氰烷型二萜类化合物——剑麻碱A-F。在光谱分析的基础上，确定了它们的立体结构。其中，粗氨酸A、B、C和E具有诱导肺叶生长因子合成的活性。进一步的研究又发现了三个同系物，分别是粗氨酸G、H和i。将大鼠嗜铬细胞瘤细胞（PC-12）与人星形细胞瘤细胞（1321Nl）的条件培养基一起培养时，这些细胞的形态发生了变化，并有神经突起的生长。三聚氰胺可增加1321Nl细胞中神经生长因子（NGF） nIRNA的表达和NGF的分泌，并呈浓度依赖性。然而，条件培养基产生的增强的神经突生长受到NGF中和抗体的轻微抑制，并且响应于酪氨酸释放的NGF浓度不足以引起分化。综上所述，新的二萜碱A和G能刺激神经营养因子的分泌，包括神经生长因子。它们是阐明神经营养因子合成和分泌机制的有用药物。

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.