Upregulatory Effects of Nobiletin, a Citrus Flavonoid with Anti-dementia Activity, on the Gene Expression of mAChR, ChAT, and CBP

Abstract

! We previously showed that nobiletin, a polymethoxylated fla-vone from the peels of Citrus depressa Hayata, improves impaired memory in dementia model animals. It was also reported that nobiletin stimulates cAMP response element-dependent transcription through activation of the cAMP response element-binding protein signaling pathway. To determine whether nobiletin alters the expression of genes involved in learning and memory, we performed real-time polymerase chain reaction after treating PC12 cells with nobiletin. Nobiletin upregulated the expression of muscarinic acetylcholine receptor subtype M1, choline acetyl-transferase, and cAMP response element-binding protein genes in the cells. The muscarinic acetylcholine receptor M1 and cho-line acetyltransferase mRNA levels reached maximum values at 6 h after nobiletin treatment, whereas the cAMP response element binding protein mRNA levels peaked at 12 h. These results suggest that nobiletin enhanced the expression of genes involved in learning and memory by stimulating the cAMP response element dependent transcription.