# The Effects of Polyphenol-Rich Black Elderly on Oxidative Stress and Hepatic Cholesterol Metabolism
###### Abstract  
Black elderberry (_Sambucus Nigar_) with high polyphenol content has been reported to have a hypolipidemic effect, but its underlying mechanisms have not been well characterized. In the present study, we investigated the effects of polyphenol-rich black elderberry (BEE) on oxidative stress and hepatic lipid metabolism. The total antioxidant activity of BEE was evaluated. The expression of genes for lipid metabolism was measured in 50 or 100 ug/mL of BEE-treated HepG2 cells. The mRNA and protein levels of genes for cholesterol metabolisms, i.e., sterol regulatory element-binding protein 2, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and low-density lipoprotein receptor, were decreased by BEE. There was marked induction of genes for high-density lipoprotein metabolism, i.e., scavenger receptor class B type 1 and ATP-binding cassette (ABC) transporter A1 in BEE-treated cells. The expression of canalicular efflux transporter for hepatic cholesterol and bile acids, such as ABCG5/G8 and ABCB11, was significantly increased by BEE treatment. There was no alteration of the lipoprotein genes, whereas BEE significantly decreased the expression of genes for fatty acid oxidation. BEE significantly altered the expression of histone deacetylase and sirtuins. These data suggest that the hypocholesterolem effects of BEE may be attributed to the alteration of genes for hepatic cholesterol synthesis and flux. black elderberry; antioxidant; cholesterol metabolism; HepG2 cells +
Footnote †: journal: Medical  
TICE pathway is an alternative route, and underlying molecular mechanisms remain unknown [8; 9]. The relative contribution of the biliary and nonbiliary pathways to cholesterol excretion is not well established. However, animal and clinical studies have reported that hepatobiliary cholesterol excretion accounts for more than 70% of fecal neutral sterols in normal metabolism [10]. Therefore, most of the studies on lowering plasma cholesterol are intensively focused on hepatic cholesterol regulation. Medications--i.e., statins, PCSK9 inhibitors, selective cholesterol absorption inhibitors, resins, fibrates, and niacin--are commonly prescribed to lower plasma cholesterol and triglycerides. However, adverse effects of these drugs include diarrhea, constipation, nausea, vomiting, stomach cramps, muscle pain, dizziness, flushing, skin rashes, heartburn, ocular disorders, and abnormal liver function [11; 12; 13; 14; 15]. Therefore, natural products and dietary agents with hypocholesterolemic effects are of intense interest. Natural products, especially polyphenol-rich foods, were claimed to have protective effects against CVD by exerting protective effects on oxidative stress, inflammation, endothelial function, and dyslipidemia [16; 17; 18; 19; 20; 21; 22]. Black elderberry (_Sambucus Nigar_), native to North America and Europe, has been widely used as supplementation to relieve cold and flu symptoms and support the immune system [23; 24]. It has a long history of use as traditional medicine for diabetes, antipsychotics, and diuretics in European countries. Studies reported that black elderberry has protective effects on preventing metabolic disease by exerting antioxidant, antiinflammatory, antibacterial, antitumor, antiobesity, hypoglycemic, and hypolipidic activity. Relatively high concentrations of polyphenols in black elderberry, particularly antiocyanins, are claimed as the bioactive components with antioxidant and anti-inflammatory effects [25; 26; 27; 28]. The major anthocyanins found in the polyphenol-rich black elderberry extract, the standardized black elderberry extract used in the present study, were cyanidin 3-glucose and cyanidin 3-sambubioside [29]. Cyanidin 3-glucose has cardioprotective effects in animal and clinical trials by modulating oxidative stress and inflammatory biomarkers [30; 31]. For cholesterol metabolism, several studies reported the effects of black elderberry in regulating cholesterol metabolism in diet-induced obesity mice and apoE knockout mice [29; 32].