Neurite outgrowth of PC12 mutant cells induced by orange oil and d-limonene via the p38 MAPK pathway.

������������������������� �������������������������������� ���������� ������������-����� ������� � We studied the effects of natural essential oil on neurite outgrowth in PC12m3 neuronal cells to eluci‑ date the mechanism underlying the action of the oils used in aromatherapy. Neurite outgrowth can be induced by nerve growth factor (NGF where ERK and p38 MAPK among MAPK pathways play important roles in activating intracellular signal transduction. In this study we investigated whether d‑limonene the major component of essential oils from oranges can promote neurite outgrowth in PC12m3 cells in which neurite outgrowth can be induced by various physical stimulations. We also examined by which pathways the ERK p38 MAPK or JNK pathway d‑limonene acts on PC12m3 cells. Our results showed that neurite outgrowth can be induced when the cells are treated with d‑limonene. After treatment with d‑limonene we observed that p38 MAPK is strongly activated in PC12m3 cells while ERK is weakly activated. In contrast JNK shows little activity. A study using an inhibitor of p38 MAPK revealed that neurite outgrowth in PC12m3 cells is induced via the activation of p38 MAPK by d‑limonene. The results thus indicate that d‑limonene may promote neural cell differen‑ tiation mainly via activation of the p38 MAPK pathway.