Long‐Term Supplementation of Black Elderberries Promotes Hyperlipidemia, but Reduces Liver Inflammation and Improves HDL Function and Atherosclerotic Plaque Stability in Apolipoprotein E‐Knockout Mice

Abstract

Scope HDL particles are protective against atherosclerosis, but may become dysfunctional during inflammation and chronic disease progression. Anthocyanin‐rich foods, such as the black elderberry, may improve HDL function and prevent disease development via antioxidant and/or anti‐inflammatory effects. This study investigates the long‐term consumption of black elderberry extract (BEE) on HDL function and atherosclerosis in apolipoprotein (apo) E−/− mice. Methods and Results ApoE−/− mice (n = 12/group) are fed a low‐fat diet, supplemented with 0, 0.25%, or 1% (by weight) BEE (≈37.5–150 mg anthocyanins per kg body weight) for 24 weeks. Feeding 1% BEE increases total serum cholesterol (+31%) and non‐HDL cholesterol (+32%) compared with the control diet. PON1 arylesterase (+32%) and lactonase (+45%) activities also increase with the 1% BEE diet. Both 0.25% BEE and 1% BEE diets strongly increase HDL cholesterol efflux capacity (CEC) by 64% and 85%, respectively. Further, BEE dose‐dependently lowers serum liver enzymes and hepatic inflammatory gene expression. Although there is no change in neutral lipid accumulation in atherosclerotic lesions, BEE promotes connective tissue deposition in the aortic root. Conclusions Chronic BEE supplementation in apoE−/− mice dose‐dependently improves HDL function. Despite BEE promoting hyperlipidemia, which likely offsets HDL effects, BEE increases connective tissue content, suggesting improved atherosclerotic plaque stability.

Anthocyanins: A Comprehensive Review of Their Chemical Properties and Health Effects on Cardiovascular and Neurodegenerative Diseases

“…Regarding pro-inflammatory genes, a down-regulation of their expression in the liver may also protect against atherosclerosis [ 180 ]. Anthocyanins reduce LDL oxidation both by increasing plasma protective enzyme activity such as that of paraoxonase 1 (PON1) [ 181 , 182 ], and decreasing the activity of enzymes such as the inducible nitric oxide synthase (iNOS), that generates strong oxidants that can readily oxidize LDL [ 183 ]. In arteries walls, monocytes differentiate into macrophages that can uptake oxLDL and form foam cells.…”

“…A recent study shows that black elderberry extract also increases cholesterol efflux capacity and decreases liver inflammation markers. Interestingly, black elderberry extract feeding enhances deposition of connective tissue in aortic roots, which may positively promote plaque stability [ 182 ].…”

Hydroxytyrosol Plays Antiatherosclerotic Effects through Regulating Lipid Metabolism via Inhibiting the p38 Signal Pathway

“…As a crucial organ for lipid metabolism, the liver plays an important role in the development of atherosclerosis [ 7 ]. For instance, blood LDL-C provides atheroprone effects and HDL-C possesses atheroprotective roles, respectively; both of which are regulated by liver cells [ 8 – 10 ]. Once the synthesis of LDL-C is enhanced or generation of HDL-C is inhibited in hepatocytes, the vascular wall has an increased risk of plaque development.…”

The Impact of Dietary Supplementation of Whole Foods and Polyphenols on Atherosclerosis

“…All the supplements were administered to ApoE −/− mice, so no genotype comparisons can be made. These studies were able to attenuate atherosclerosis to some degree, except for black elderberry, which promoted collagen deposition into the plaque, making it more stable and less likely to rupture which is beneficial [119]. Of note, our study on blackberry reduced plaque only in males, but not in females [114].…”

“…Frozen fruit consumption is on the rise, which is interesting because frozen fruits retain more vitamins than fresh fruits or vegetables due to flash freezing [111,112]. Our literature search yielded seven berry studies-including acai berry [113], blackberry [114], blueberry [115], lingonberry [116], hawthorn berry [117], bilberry [118], and black elderberry extract [119]-that matched our review criteria. Blackberries from the northern US, blueberry from the southern states such as Florida and California, and acai berry from South America are common in American cuisine, but the other berries are less known.…”