Figure 3.

The crosstalk between AMPK, Nrf2, and SIRT1 pathways in the anti-inflammatory effect of phloretin. The activation of AMPK and SIRT1 are closely related in the regulation of metabolism and pathologies such as oxidative stress and inflammation. Activation of AMPK by phloretin via its phosphorylation as well as increased expression of SERT1 have been associated with its anti-inflammatory effect and modulation of lipid metabolism such as inhibition of lipid accumulation. This activity was further shown to be related to the induction of Nrf2 that suppresses both the oxidative stress and inflammatory pathways induced by a variety of agents including LPS. Increased SERT3 activity by phloretin is also reported. The red line shows the inhibitory response.