Limonene Enhances the cAMP Response Element (CRE)-Dependent Transcriptional Activity Activated via Adenosine A2 A Receptor in a Neural-Crest Derived Cell Line, PC-12

Prevention and treatment of Alzheimerʼs disease are urgent problems for elderly people in developed countries. To seek useful compounds that treat, delay the onset, or prevent the development of Alzheimerʼs disease, we screened natural resources using the cyclic AMP response element-dependent transcription in the PC12 cell line. We previously found that honey bee royal jelly stimulates the cyclic AMP response element-dependent transcription activity in PC12 cells. Here, we report that R-limonene, a monoterpene, enhanced the royal jelly-induced cyclic AMP response element-dependent transcription activity, whereas R-limonene showed no effect in absence of royal jelly. The enhancement was inhibited by ZM241385, an antagonist for adenosine A2 A receptor. R-limonene also enhanced the cyclic AMP response element-dependent transcription activity activated by adenosine and AMP. Thus, R-limonene represents a novel type of modulator that enhances the CRE-dependent transcription via adenosine A2 A receptor pathway.