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J.Health Sci., 51(6), 687-692, 2005

Neurotrophic Effects of Genipin on Neuro2a Cells

Matsumi Yamazaki*, a and Kenzo Chibaa, b

aDepartment of Biochemistry, Faculty of Pharmaceutical Sciences, and bOrganization for Frontier Research in Preventive Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa, Ishikawa 920-1181, Japan

We have found that genipin, a herbal iridoid compound, can induce neurite outgrowth in rat pheochromocytoma PC12h cells. In this study, we examined the neurotrophic effects of genipin in mouse neuroblastoma Neuro2a cells. Genipin significantly induced neurite outgrowth in a concentration-dependent manner in Neuro2a cells cultured in serum-free medium supplemented with transferrin/insulin/progesterone (TIP) without cytotoxicity. Neuro2a cells cultured in serum-containing medium were mitotic, while the proliferation of these cells cultured in serum-free medium supplemented with TIP was suppressed for up to 48 hr. Serum and TIP-free medium clearly increased the number of cells stained with trypan blue compared with serum-free medium supplemented with TIP. Damage to the cells was significantly reduced by adding genipin to the cells in serum and TIP-free medium. As a positive control for a neurotrophic action, dibutyryl cAMP, a membrane-permeable cAMP analog, also induced neuritogenesis in cells cultured in serum-free medium supplemented with TIP and enhanced the survival of cells cultured in serum and TIP-free medium. These results indicate that genipin has both neuritogenic activity and a survival effect on serum-deprivation-induced cell death in Neuro2a cells. This suggests that genipin can act as a neurotrophic factor-like compound in neuronal cells.