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 flavone 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 acetyltransferase, and cAMP response element-binding protein genes in the cells. The muscarinic acetylcholine receptor M1 and choline 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.