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A Boost in Mitochondrial Activity Underpins the Cholesterol-Lowering Effect of Annurca Apple Polyphenols on Hepatic Cells

1
Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano, SA, Italy
2
Department of Pharmacy, University of Naples Federico II. Via Montesano 49, 80149 Naples, Italy
3
PhD Program in Drug Discovery and Development, University of Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano, SA, Italy
4
Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, 80149 Naples, Italy
*
Authors to whom correspondence should be addressed.
Equally contributing.
Nutrients 2019, 11(1), 163; https://doi.org/10.3390/nu11010163
Received: 24 November 2018 / Revised: 21 December 2018 / Accepted: 11 January 2019 / Published: 14 January 2019
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. View Full-Text
Keywords: nutraceuticals; apple polyphenols; procyanidin B2; anti-oxidants; cholesterol; statins nutraceuticals; apple polyphenols; procyanidin B2; anti-oxidants; cholesterol; statins
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Sommella, E.; Badolati, N.; Riccio, G.; Salviati, E.; Bottone, S.; Dentice, M.; Campiglia, P.; Tenore, G.C.; Stornaiuolo, M.; Novellino, E. A Boost in Mitochondrial Activity Underpins the Cholesterol-Lowering Effect of Annurca Apple Polyphenols on Hepatic Cells. Nutrients 2019, 11, 163.

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