Identification of AMP N1-oxide in royal jelly as a component neurotrophic toward cultured rat pheochromocytoma PC12 cells

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 Nsub(1) -oxide. AMP Nsub(1) oxide was more than 20 times as active as AMP, judging from the minimal concentration to elicit activity. AMP Nsub(1)-oxide was thought to be responsible for about half of the process-forming activity of whole RJ. Chemically-synthesized AMP Nsub(1)-oxide was active similarly to the molecule purified from RJ, confirming AMP Nsub(1)-oxide as the active entity. AMP Nsub(1)-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 Nsub(1)-oxide to induce neuronal differentiation of PC12 cells. Pharmacological experiments suggested that AMP Nsub(1)-oxide actions are mediated by adenyl cyclase-coupled adenosine receptors, including Asub(2A). Thus AMP Nsub(1)-oxide is a key molecule that characterizes RJ, and is not found in natural products other than RJ.