The Multifunctional Effects of Nobiletin and Its Metabolites In Vivo and In Vitro

Figure 2

The possible signaling cascades of NOB in cells. NOB may upregulate the activities of NMDA receptor and ERK and enhance CREB transcriptional activity. NOB may restore the activity of DARPP-32 through modulation of PKA signaling pathway. Ca²⁺/CaMKII signaling is also enhanced by NOB, leading to upregulation of CREB transcription. In addition, NOB increases the activities of PI3K/Akt and BDNF/TrkB signaling but upregulates the expression of PPARγ. However, it depends on different cell lines. Insulin sensitization has been elevated by NOB through Nrf2 signaling pathway.