Abstract
Reduction in cholesterol blood levels represents one of the therapeutic goals to achieve in order to reduce the occurrence of cardiovascular diseases. Commonly, this goal is attempted by promoting healthy lifestyle behaviors and low-fat diets. Recently, several nutraceuticals have been shown to possess cholesterol-lowering properties and are becoming common over the counter products. Among others, apple polyphenols efficiently lower total cholesterol levels in humans and impact overall lipid metabolism. Malus Pumila Miller cv Annurca is an apple native to Southern Italy presenting one of the highest content of procyanidin B2, a dimeric procyanidin. Tested in clinical trials, the oral consumption of an Annurca polyphenolic extract (AAE) exerted a cholesterol-lowering effect similar to the statins Atorvastatin and Simvastatin. Despite AAE activity, the analysis of the molecular mechanism behind its cholesterol-lowering effect is unclear. Using isotope labeling and high-resolution mass spectrometry approaches we here performed a metabolic profiling of in vitro cultured human hepatocytes treated with AAE to reveal its mechanism of action. The results show that AAE acts differently than statins. The extract reprograms hepatic cell metabolism and promotes mitochondrial respiration, lipolysis and fatty acid β-oxidation. Citrate and acetyl-CoA, both necessary for the production of cholesterol, are diverted to the Krebs Cycle by AAE, that, ultimately, lowers cholesterogenesis and fatty acid synthesis.
Highlights
Cardiovascular diseases (CVDs) kill more than 4 million people in the world each year accounting for approximately 27% and 32% of all deaths among males and females, respectively [1,2]
Our previously published studies have already shown that Annurca polyphenolic extract (AAE) reduces total cholesterol levels both in vitro, in hepatic cultured cells, as well as in vivo, in humans affected by mild hypercholesterolemia [29,42]
Statins, used for the prevention and treatment of hypercholesterolemia, improves cholesterol levels via inhibition of Hydroxymethyl Glutaryl Coenzyme A (HMG-CoA) reductase a rate-limiting enzyme involved in cholesterol biosynthesis
Summary
Cardiovascular diseases (CVDs) kill more than 4 million people in the world each year accounting for approximately 27% and 32% of all deaths among males and females, respectively [1,2]. Nutrients 2019, 11, 163 undisputed and is being attempted by promoting healthy lifestyle behaviors (e.g., low-fat diet, physical activity, smoking cessation) and by controlling lipids blood levels in individuals at moderate or at high risk of CVDs [1,3,4]. More than half of the reduction in CVD mortality has been attributed to reduction in cholesterol and blood pressure levels. Statins are the most common drugs recommended for primary prevention of CVD and are widely prescribed in the treatment of hypercholesterolemia [5].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
