Inhibition of Low Density Lipoprotein-oxidation, ACAT-1, and ACAT-2 by Lignans from the Bark of Machilus thunbergii

The bark of Machilus thunbergii was extracted with 80% aqueous methanol (MeOH), and the concentrated extract was partitioned using ethyl acetate (EtOAc), butanol (n-BuOH), and H₂O, successively. From the EtOAc fraction, five lignans were isolated through the repeated silica gel, octadecyl silica gel (ODS) and, Sephadex LH-20 column chromatography. Based on nuclear magnetic resonance (NMR), mass spectroscopy (MS), and infrared spectroscopy (IR) spectroscopic data, the chemical structures of the compounds were determined to be machilin A (1), machilin F (2), licarin A (3), nectandrin A (4), and nectandrin B, (5). This study presents comparative account of five lignans from M. thunbergii bark contributing inhibition of low density lipoprotein (LDL), ACAT-1, and ACAT-2. Compounds 2-5 showed varied degree of antioxidant activity on LDL with IC∧50 values of 2.1, 11.8, 15.3, and 4.1 μM. Compounds 1, 2, and 3 showed inhibition activity on ACAT-1 with values 63.4±6.9% (IC∧50=66.8 μM), 53.7±0.9% (IC∧50=109.2 μM), and 78.7±0.2% (IC∧50=40.6 μM), respectively, at a concentration of 50 mg/mL, and on ACAT-2 with values 47.3±1.5% (IC∧50=149.7 μM), 39.2±0.2% (IC∧50=165.2 μM), and 52.1±1.0% (IC∧50=131.0 μM), respectively, at a concentration of 50 mg/mL.