Black Elderberry Extract Improves Serum HDL‐cholesterol and Paraoxonase‐1 Activity in Atherosclerosis‐Prone Mice

Abstract

Cardiovascular disease (CVD) is one of the most prevalent non‐communicable diseases in the United States, claiming upwards of 600,000 lives per year. Excessive plaque accumulation and atherosclerosis are hallmark characteristics of this disease. HDL is responsible for the removal of deposited cholesterol in the arteries to the liver for excretion, a process known as reverse cholesterol transport. Low levels of high‐density lipoprotein cholesterol (HDL‐C) have been correlated with increased risk for CVD in epidemiological studies. However, drug therapies targeting an increase in HDL‐C have failed to demonstrate a reduced risk. More recently, HDL particle functionality rather than HDL‐C concentration, has been suggested to be a better predictor of CVD risk. Ingestion of bioactive dietary components, such as polyphenols, may increase both HDL‐C concentration and HDL functionality. Black elderberry (Sambucus nigra) contains high amounts of anthocyanins (~1300 mg/100 g), a subclass of polyphenols, relative to other edible berries. We investigated whether the consumption of a black elderberry extract (BEE) influenced lipid metabolism, HDL functionality, and atherosclerosis in a mouse model of hypercholesterolemia (apoE−/− mice). We fed male apoE−/− (n = 12/group) ad libitum a low‐fat AIN‐93M diet supplemented with 0 or 1% (by weight of diet; ~150 mg anthocyanins/kg body weight) black elderberry extract (BEE) for 24 weeks. Supplementation with BEE significantly increased total cholesterol (+31.5%) and HDL‐C (+26%), while triglycerides were not significantly changed. Paraoxonase‐1 (PON1), a lipolactonase enzyme carried by HDL which prevents lipoprotein oxidation, was increased by 32% in the treatment group when compared to controls (p < 0.05). Analysis of hepatic gene expression revealed that BEE significantly increased expression of Nrf2 and GClc (p < 0.05), both of which are important for endogenous antioxidant defense and may be related to the significant reductions in serum alanine transaminase and aspartate transaminase levels in the BEE treatment group (p < 0.05). Despite improved markers of HDL‐C and HDL function, en face analysis of aortas showed no difference in severity of atherosclerosis between groups. The current data suggests that BEE supplementation improves HDL‐C and HDL function, while also upregulating genes involved in the endogenous antioxidant defense.Support or Funding InformationSupported by the USDA National Institute of Food and Agriculture, #1005610 and Hatch project #1003343.