With a history of several thousand years, Traditional Chinese Medicine (TCM) is an invaluable source of’ “pre-screened” drugs that are efficacious in treating various disorders. An in vitro model system, rat pheochromocytoma cells (PC 12), was used to study potential neuroactive compounds present in TCM, such as Melia toosendan. Treatment of Melia toosendan can reduce the cell proliferation rate of PC 12 cells. In the presence of serum, PC 12 cells treated with a crude extract of Melia toosendan induced the neuronal differentiation. However, this phenomenon was attenuated with low serum medium. Furthermore, incubation of Melia toosendan activates various signaling pathways in PC 12 cells, including MAP kinase pathways, PKC pathway and PI-3 kinase pathway....[ Read more ]

With a history of several thousand years, Traditional Chinese Medicine (TCM) is an invaluable source of’ “pre-screened” drugs that are efficacious in treating various disorders. An in vitro model system, rat pheochromocytoma cells (PC 12), was used to study potential neuroactive compounds present in TCM, such as Melia toosendan. Treatment of Melia toosendan can reduce the cell proliferation rate of PC 12 cells. In the presence of serum, PC 12 cells treated with a crude extract of Melia toosendan induced the neuronal differentiation. However, this phenomenon was attenuated with low serum medium. Furthermore, incubation of Melia toosendan activates various signaling pathways in PC 12 cells, including MAP kinase pathways, PKC pathway and PI-3 kinase pathway.

In the present study, results further demonstrated that combined treatment of PC12 cells with both Melici toosendan and NGF resulted in enhanced neurite elongation. While little is known regarding the molecular mechanism underlying this synergistic effect of Melia toostwdan and NGF, these findings suggest that this effect was independent of PI-3 kinase and PKC pathways but dependent on ERK and PKA pathways. Data indicated that the synergistic effects were likely due to the enhancement of NGF-induced ERK1/2 activity. Although other members of MAP kinase family (p38 and JNK) were also activated in Melia toosendan signaling, the ERK pathway had a predominant role over the others since the inhibition of ERK1/2 activity blocked the synergistic effect on PC 12 cell differentiation. More importantly, it was observed that PKA played a critical role in the ERK1/2 super-activation and synergistic effect on PC12 cell differentiation induced by both NGF and Melia toosendan.