Licochalcone B attenuates atherosclerosis through the suppression of endothelial inflammation by targeting the KEAP1/NRF2/NF-κB axis, exhibiting no hepatotoxicity or nephrotoxicity.
LCB treatment significantly attenuated atherosclerotic progression in ApoE-/- mice fed a high-fat diet.
LCB directly targeted KEAP1 in endothelial cells, promoting its autophagic degradation.
LCB initiated an NRF2-dependent antioxidant response downstream of KEAP1 degradation.
LCB downregulated VCAM1 and ICAM1 expression in inflamed endothelial cells.
LCB exhibited no hepatotoxicity or nephrotoxicity in the experimental model.
This study provides the first demonstration that LCB attenuates atherosclerosis through endothelial inflammation suppression via the KEAP1/NRF2/NF-κB axis.
This research suggests that Licochalcone B (LCB), a natural compound derived from licorice root, may have therapeutic potential against atherosclerosis — the buildup of plaques in artery walls that is a leading cause of heart attacks and strokes. In mice genetically prone to developing atherosclerosis and fed a high-fat diet, eight weeks of LCB treatment reduced the size of arterial plaques and made existing plaques more stable (less likely to rupture), with effects comparable to the commonly used cholesterol-lowering drug simvastatin. Importantly, LCB caused no detectable liver or kidney damage during treatment. The researchers also investigated how LCB works at the molecular level in blood vessel lining cells (endothelial cells). They found that LCB physically binds to a protein called KEAP1 and promotes its degradation through a cellular recycling process called autophagy. This sets off a chain reaction: degrading KEAP1 activates a protective protein called NRF2, which in turn blocks a key inflammation-driving protein called NF-κB from being activated. The end result is reduced production of adhesion molecules (VCAM1 and ICAM1) that normally help immune cells stick to and invade artery walls — a critical early step in atherosclerosis development. This research suggests that LCB could represent a promising natural compound for developing new treatments for atherosclerotic cardiovascular disease, working through a distinct mechanism from current standard-of-care drugs. However, these findings are based on animal and cell culture models, and further research including clinical trials in humans would be necessary before any conclusions about human therapeutic use could be drawn.
Liao Z, Zhou W, Du S, Liu X, Yao J, Din Z, et al.. (2026). Licochalcone B alleviates atherosclerosis by inhibiting endothelial inflammation via targeting the KEAP1/NRF2/NF-κB signalling pathway.. Phytomedicine : international journal of phytotherapy and phytopharmacology. https://doi.org/10.1016/j.phymed.2026.158333