Melia toosendan regulates PC12 Cell differentiation via the activation of protein kinase A and extracellular signal-regulated kinases

With a history of several thousand years, traditional Chinese medicine has been well documented to be effective in the treatment of various disorders. We have investigated the activities of potential neuroactive compounds in traditional Chinese medicine such as Melia toosendan using an in vitro model system, rat pheochromocytoma PC12 cells. We report here that treatment of PC12 cells with a crude extract of the fruits of M. toosendan reduces cell growth in a dose-dependent manner without detectable cytotoxicity. Upon treatment with M. toosendan, PC12 cells exhibit robust neurite outgrowth, to a greater extent than that observed with nerve growth factor. Results obtained with specific kinase inhibitors and protein kinase A-deficient PC12 cells indicate that the actions of M. toosendan are mediated by the activation of protein kinase A and extracellular signal-regulated kinases.