INIBIOLP (La Plata Biochemical Research Institute), CONICET-CCT La Plata, School of Medical Sciences, UNLP, 60 y 120 (1900), La Plata, Argentina.
LIDeB (Laboratory of Bioactive Research and Development), Medicinal Chemistry, Department of Biological Sciences, School of Exact Sciences, UNLP, 47 y 115 (1900), La Plata, Argentina.
Nutr Metab Cardiovasc Dis. 2020 Aug 28;30(9):1590-1599. doi: 10.1016/j.numecd.2020.04.033. Epub 2020 May 12.
Hypercholesterolemia and oxidative stress are two of the most important risk factors for atherosclerosis. The aim of the present work was to evaluate mandarin (Citrus reticulata) peel oil (MPO) in cholesterol metabolism and lipid synthesis, and its antioxidant capacity.
Incubation of hepatic HepG2 cells with MPO (15-60 μL/L) reduced cholesterogenesis and saponifiable lipid synthesis, demonstrated by [C]acetate radioactivity assays. These effects were associated with a decrease in a post-squalene reaction of the mevalonate pathway. Molecular docking analyses were carried out using three different scoring functions to examine the cholesterol-lowering property of all the components of MPO against lanosterol synthase. Docking simulations proposed that minor components of MPO monoterpenes, like alpha-farnesene and neryl acetate, as well the major component, limonene and its metabolites, could be partly responsible for the inhibitory effects observed in culture assays. MPO also decreased RAW 264.7 foam cell lipid storage and its CD36 expression, and prevented low-density lipoprotein (LDL) lipid peroxidation.
These results may imply a potential role of MPO in preventing atherosclerosis by a mechanism involving inhibition of lipid synthesis and storage and the decrease of LDL lipid peroxidation.
高胆固醇血症和氧化应激是动脉粥样硬化最重要的两个危险因素。本研究旨在评估橘红（Citrus reticulata）皮油（MPO）在胆固醇代谢和脂质合成中的作用及其抗氧化能力。
用 MPO（15-60 μL/L）孵育 HepG2 细胞，通过 [C]乙酸放射性标记实验显示，MPO 降低了胆固醇生成和可皂化脂质合成。这些作用与鲨烯途径的前鲨烯反应减少有关。使用三种不同的评分函数对 MPO 的所有成分进行了分子对接分析，以研究 MPO 对羊毛甾醇合酶的降胆固醇特性。对接模拟提出，MPO 的非萜烯类次要成分，如法呢烯和乙酸橙花酯，以及主要成分柠檬烯及其代谢物，可能部分负责观察到的在培养实验中的抑制作用。MPO 还降低了 RAW 264.7 泡沫细胞的脂质储存及其 CD36 表达，并防止了低密度脂蛋白（LDL）的脂质过氧化。
这些结果可能意味着 MPO 通过抑制脂质合成和储存以及降低 LDL 脂质过氧化作用，在预防动脉粥样硬化方面具有潜在作用。
