Susilowati Retno, Jannah Jauharotul, Maghfuroh Zahrotul, Kusuma Meike Tiya
Department of Biology, Faculty of Science and Technology, State Islamic University of Maulana Malik Ibrahim (UIN), Malang, East Java, Indonesia.
Master Program of Biology, Postgraduate Program, State Islamic University of Maulana Malik Ibrahim (UIN), Malang, East Java, Indonesia.
J Adv Pharm Technol Res. 2020 Jul-Sep;11(3):128-133. doi: 10.4103/japtr.JAPTR_28_20. Epub 2020 Jul 14.
Hyperlipidemia is generally managed with statin-based drugs. Simvastatin serves as a 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitor, with prolonged use proven to cause side effects. In the present study, antihyperlipidemic material is tested for its effect in lowering lipid in animals and its proven ability to bind to HMGR. Hyperlipidemia rats were divided into four groups, with different doses of 0, 57, and 114 mg/kg BW of apple peel extract (APE) and simvastatin (3.6 mg/kg BW). The total cholesterol (TC), total triglyceride (TG), low-density lipoprotein cholesterol (LDLc), and high-density lipoprotein cholesterol (HDLc) serum were measured. In silico inhibition test of HMGR activity was conducted by molecular docking using PyRx software. This process places HMGR as a receptor and active compound of apple peels as a ligand. APE treatment with a dose of 114 mg/kg BW could significantly reduce LDLc and increase serum HDLc levels. Docking tests confirmed that quercetin, chlorogenic acid, epicatechin, and catechins depicted HMGR inhibition. Quercetin could bind to HMGR at a similar location to amino acid residues as simvastatin. These material extracts have inhibited cholesterol synthesis through a stronger HMGR inhibition than simvastatin.
高脂血症通常用他汀类药物治疗。辛伐他汀是一种3-羟基-3-甲基戊二酰辅酶A还原酶（HMGR）抑制剂，长期使用已证明会产生副作用。在本研究中，对降血脂物质进行了动物降血脂效果及其与HMGR结合能力的测试。将高脂血症大鼠分为四组，分别给予0、57和114mg/kg体重的苹果皮提取物（APE）以及辛伐他汀（3.6mg/kg体重）不同剂量。测定血清总胆固醇（TC）、总甘油三酯（TG）、低密度脂蛋白胆固醇（LDLc）和高密度脂蛋白胆固醇（HDLc）。使用PyRx软件通过分子对接进行HMGR活性的计算机模拟抑制试验。该过程将HMGR作为受体，苹果皮的活性化合物作为配体。114mg/kg体重剂量的APE处理可显著降低LDLc并提高血清HDLc水平。对接试验证实，槲皮素、绿原酸、表儿茶素和儿茶素表现出对HMGR的抑制作用。槲皮素可在与辛伐他汀相同的氨基酸残基位置与HMGR结合。这些物质提取物通过比辛伐他汀更强的HMGR抑制作用抑制了胆固醇合成。
