Hattori Noriko, Nomoto Hiroshi, Mishima Satoshi, Inagaki Shinsuke, Goto Masashi, Sako Magoichi, Furukawa Shoei
Laboratory of Molecular Biology, Gifu Pharmaceutical University, Gifu, Japan.
Biosci Biotechnol Biochem. 2006 Apr;70(4):897-906. doi: 10.1271/bbb.70.897.
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 A2A. Thus AMP N1-oxide is a key molecule that characterizes RJ, and is not found in natural products other than RJ.
蜂王浆提取物可诱导培养的大鼠嗜铬细胞瘤PC12细胞发生变化。分离出了活性成分，并鉴定为单磷酸腺苷（AMP）和AMP N1-氧化物。从引发活性的最低浓度判断，AMP N1-氧化物的活性是AMP的20倍以上。AMP N1-氧化物被认为约占整个蜂王浆促变化活性的一半。化学合成的AMP N1-氧化物与从蜂王浆中纯化的分子具有相似的活性，证实AMP N1-氧化物为活性成分。AMP N1-氧化物还可抑制PC12细胞的增殖，并刺激成熟神经元的特异性蛋白神经丝蛋白M的表达，表明AMP N1-氧化物具有诱导PC12细胞神经元分化的刺激活性。药理学实验表明，AMP N1-氧化物的作用是由包括A2A在内的与腺苷酸环化酶偶联的腺苷受体介导的。因此，AMP N1-氧化物是表征蜂王浆的关键分子，除蜂王浆外，在其他天然产物中未发现。
