Anthocyanin‐rich Black Elderberry Extract Improves Markers of HDL Function and Reduces Aortic Cholesterol in Hyperlipidemic Mice

Abstract

Atherosclerosis is a chronic inflammatory disease and is associated with impairments in high‐density lipoprotein (HDL) function, including reductions in HDL‐cholesterol, antioxidant and anti‐inflammatory activities. Anthocyanins are polyphenols with anti‐inflammatory properties. We investigated whether an anthocyanin‐rich black elderberry extract (Sambucus nigra) (BEE) (13% anthocyanins) would protect against inflammation‐related impairments in HDL function and atherosclerosis in apoE‐/‐ mice. We fed an AIN‐93M diet supplemented with 1.25% (wt/wt) BEE or control diet to 10 week old male apoE‐/‐ mice for 6 weeks. The BEE fed to mice was rich in cyanidin 3‐sambubioside (~9.8% wt/wt) and cyanidin 3‐glucoside (~3.8% wt/wt). After 6 weeks, serum lipids did not differ significantly between groups, while aspartate transaminase (AST) and fasting glucose were reduced in BEE‐fed mice. Hepatic and intestinal mRNA changes with BEE‐feeding were consistent with an improvement in HDL function (Apoa1, Pon1, Saa1, Lcat, Clu) and a reduction in hepatic cholesterol levels (increased Ldlr and Hmgcr, reduced Cyp7a1). In BEE‐fed mice, serum paraoxonase‐1 activity was significantly higher. In addition, mice fed BEE had significantly lower serum chemokine (C‐C motif) ligand 2 (CCL2) and tended to have lower serum thiobarbituric acid reactive substances compared to control‐fed mice. Notably, we observed significant reductions in total cholesterol content of the aorta of BEE‐fed mice, indicating less atherosclerosis progression. These findings suggest that black elderberry may be useful to prevent HDL dysfunction associated with chronic inflammation. [Supported by the USDA Hatch Project #1003343].