title: Anthocyanin-rich black elderberry extract improves markers of HDL function and reduces aortic cholesterol in hyperlipidemic mice.
abstract: Serum high-density lipoprotein-cholesterol (HDL-C) is a risk factor considered to be protective of atherosclerosis. However, atherosclerosis is an inflammatory disease and contributes to impairment in high-density lipoprotein (HDL) function, including reductions in HDL-C, HDL antioxidant and anti-inflammatory activities. Anthocyanins are polyphenols that have demonstrated antioxidant and anti-inflammatory properties. The objective of this study was to determine 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, a mouse model of hyperlipidemia and HDL dysfunction. We fed an AIN-93M diet supplemented with 1.25% (w/w) 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% w/w) and cyanidin 3-glucoside (∼ 3.8% w/w). 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 (PON1) arylesterase activity was significantly higher. In addition, mice fed BEE had significantly lower serum chemokine (C-C motif) ligand 2 (CCL2) 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. This study suggests that black elderberry may have the potential to influence HDL dysfunction associated with chronic inflammation by impacting hepatic gene expression.
authors.affiliation: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA. christopher.blesso@uconn.edu.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Farrell
authors.forename: Gregory
authors.initials: G
authors.lastname: Norris
authors.forename: Sang Gil
authors.initials: SG
authors.lastname: Lee
authors.forename: Ock K
authors.initials: OK
authors.lastname: Chun
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Blesso
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics; D001055:Apolipoproteins B / Q000097:blood; D043303:Aryldialkylphosphatase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D018932:Chemokine CCL2 / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D004187:Disaccharides / Q000494:pharmacology*; D004195:Disease Models, Animal; D005960:Glucosides / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000097:blood*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010936:Plant Extracts / Q000494:pharmacology*; D027924:Sambucus nigra / Q000737:chemistry*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D000872:Anthocyanins; D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D015415:Biomarkers; D001786:Blood Glucose; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D008076:Cholesterol, HDL; D004187:Disaccharides; D005960:Glucosides; D010936:Plant Extracts; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; C462279:cyanidin-3-O-beta-glucopyranoside; C546691:cyanidin 3-sambubioside; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D043303:Aryldialkylphosphatase