Identification of AMP N₁-Oxide in Royal Jelly as a Component Neurotrophic toward Cultured Rat Pheochromocytoma PC12 Cells

Abstract

An extract of royal jelly (RJ) induced processes from cultured rat pheochromocytoma PC12 cells. Active components were isolated, and identified as adenosine monophosphate (AMP) and AMP N₁-oxide. AMP N₁-oxide was more than 20 times as active as AMP, judging from the minimal concentration to elicit activity. AMP N₁-oxide was thought to be responsible for about half of the process-forming activity of whole RJ. Chemically-synthesized AMP N₁-oxide was active similarly to the molecule purified from RJ, confirming AMP N₁-oxide as the active entity. AMP N₁-oxide also suppressed proliferation of PC12 cells and stimulated expression of neurofilament M, a specific protein of mature neurons, demonstrating the stimulatory activity of AMP N₁-oxide to induce neuronal differentiation of PC12 cells. Pharmacological experiments suggested that AMP N₁-oxide actions are mediated by adenyl cyclase-coupled adenosine receptors, including A_{2 A}. Thus AMP N₁-oxide is a key molecule that characterizes RJ, and is not found in natural products other than RJ.