Figure 7. Schematic diagram showing the effect of nimbolide on P-glycoprotein expression and the involved molecular mediators.

Nimbolide-mediated P-glycoprotein downregulation is accomplished through targeting PTEN and MYC. PI3K/AKT/mTOR signaling pathway regulates NF-κB translocation and transcriptional activity through IKK phosphorylation. The inhibition of PI3K/AKT/mTOR leads to increasing HIF1α degradation and FoxO1 activation. The latter antagonizes MYC activity and decreases cellular ROS level.