FIG. 9.

Schematic overview of the crosstalk between AMPK and Nrf2 pathways induced by BBR in LPS-stimulated inflammation. It was known that LPS activates NF-κB pathway and prompts inflammation through TLR4, and Nrf2 activation is crucial for antioxidative and anti-inflammation reaction. One the other hand, comparing to its homeostatic effect on energy metabolism, the anti-inflammatory role of AMPK is a lately finding with mechanistic unknowns. Based on the present study, we propose a cascade-flow initiated by berberine in LPS-treated macrophages, which starts from AMP/ATP ratio elevation and AMPK activation, but goes to the phosphorylation and nuclear distribution of Nrf2 protein, the up-regulation of Nrf2-targeted antioxidative genes, the suppression of NF-κB-mediated inflammatory response, the reduced ROS production and even alleviated in vivo inflammation, sequentially. Thus, the interaction between AMPK and Nrf2 pathways plays an important role in inflammation suppression. ↓, activation; ⊥, inhibition.