Cardamonin targets KEAP1/NRF2 signaling for protection against atherosclerosis
Pengfei Fan, Huali Meng, Wenhao Hao, Zheng Yan, Hui Li, Zhiyue Zhang, Lei Du, Xin Guo, Dongliang Wang, Yunyan Wang, Hao Wu
Abstract
gene. Surprisingly, AHR was not required for CAD's action on the activation of NRF2/HO1 signaling since AHR gene silencing did not reverse this effect. Furthermore, a molecular docking assay showed a strong binding potential of CAD to the Kelch domain of the Kelch-like ECH-associated protein 1 (KEAP1) which sequesters NRF2 in the cytoplasm. Both CAD and the Kelch domain inhibitor Ki696 promoted NRF2 nuclear translocation, whereas the combination of CAD and Ki696 did not yield a greater effect compared with either CAD or Ki696, confirming the interaction of CAD with the Kelch domain. This work provides an experimental basis for CAD as a novel and effective bioactive food component in future AS interventions.