<i>Lonicera caerulea</i> Berry Polyphenols Regulate Cholesterol Metabolism in Rats With Type 2 Diabetes by Activating SIRT1 Expression in Macrophages and Reducing Foaming

ABSTRACT Lonicera caerulea berry polyphenols (LCBP) exhibit multiple physiological effects. In this study, we investigated the role of LCBP in reducing cholesterol accumulation in rats with type 2 diabetes mellitus (T2DM) and its underlying mechanism. LCBP reduced the content of neutral lipids in the aorta and decreased the plaque area by 47.3% ( p &lt; 0.01) compared with that in the model group. LCBP also reduced the expression of CD11b and F4/80 in peritoneal macrophages. The cholesterol efflux rate in the LCBP group increased significantly by 61.2% ( p &lt; 0.01). Western blotting and immunohistochemical experiments revealed that LCBP promoted cholesterol efflux via a dual mechanism of activating silent information regulator 1 (SIRT1) in macrophages in a high‐glucose environment and the miR‐33/SREBP2‐ABCA1 pathway. SIRT1 activation enhanced the effects of LCBP on cholesterol regulation. Molecular dynamics simulation experiments revealed that the three main monomer components of LCBP—cyanidin‐3‐glucoside, catechin, and chlorogenic acid—could stably bind to the active site of SIRT1 and serve as key components in the regulation of cholesterol by this protein. This study provides new insights into the use of LCBP as a functional food additive for T2DM‐related atherosclerosis.