Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano, SA, Italy.
Department of Pharmacy, University of Naples Federico II. Via Montesano 49, 80149 Naples, Italy.
Nutrients. 2019 Jan 14;11(1):163. doi: 10.3390/nu11010163.
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. 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.
降低胆固醇水平是实现降低心血管疾病发生的治疗目标之一。通常，通过促进健康的生活方式行为和低脂肪饮食来实现这一目标。最近，几种营养保健品已被证明具有降低胆固醇的特性，并成为常见的非处方产品。其中，苹果多酚能有效降低人体的总胆固醇水平，并影响整体脂质代谢。 cv Annurca 是一种原产于意大利南部的苹果，含有最高的二聚原花青素 B2（procyanidin B2）之一。临床试验测试表明，口服摄入安努卡多酚提取物（AAE）具有与他汀类药物阿托伐他汀和辛伐他汀相似的降胆固醇作用。尽管 AAE 具有活性，但对其降胆固醇作用背后的分子机制的分析尚不清楚。在这里，我们使用同位素标记和高分辨率质谱分析方法，对用 AAE 处理的体外培养的人肝细胞进行代谢组学分析，以揭示其作用机制。结果表明，AAE 的作用不同于他汀类药物。该提取物重新编程肝细胞代谢，促进线粒体呼吸、脂肪分解和脂肪酸β氧化。柠檬酸和乙酰辅酶 A 都是胆固醇生成所必需的，AAE 将其分流到三羧酸循环中，最终降低胆固醇生成和脂肪酸合成。
