5‐Heptadecylresorcinol Protects against Atherosclerosis in Apolipoprotein E‐Deficient Mice by Modulating SIRT3 Signaling: The Possible Beneficial Effects of Whole Grain Consumption

Scope Whole grain consumption has been proven to be inversely associated with the risk of cardiovascular diseases. As a biomarker for whole grain dietary intake, 5‐heptadecylresorcinol (AR‐C17) has attracted increased attention due to its potential health‐improving activity. However, the beneficial effect of AR‐C17 on atherosclerosis prevention and the underlying mechanism remain unclear. Methods and Results High‐fat diet fed apolipoprotein E‐deficient (ApoE−/−) mice are administrated with or without AR‐C17 (30 and 150 mg kg−1) for 16 weeks. Histological staining is performed for plaque analysis. Immunofluorescence, western blot, and seahorse cell analysis are carried out to investigate the action of mechanism of AR‐C17. The results indicate that AR‐C17 supplementation lowered serum total cholesterol, triglyceride, VLDL‐C, and LDL‐C levels. Moreover, the atherosclerotic plaques in the aortic root region of mice heart are significantly reduced by AR‐C17 intervention compared with ApoE−/− control group. In addition, AR‐C17 treatment alleviates endothelial cell damage and apoptosis by improving mitochondrial function via sirtuin3 signaling pathway both in ApoE−/− mice and oxidized‐LDL‐treated human umbilical vein endothelial cells. Conclusion AR‐C17 may be applied as a promising grain‐based dietary bioactive ingredient for atherosclerosis prevention. Meanwhile, as a mitochondrial protective agent, it can offer support for the suggested health claim of whole grain diet.