Acid-Catalyzed Synthesis of Octacosanyl Fatty Acid Esters and Their In Vivo Biological Activities

Abstract

Octacosanol (C28), mainly found in rice bran and sugar cane, possesses cholesterol-lowering properties but is limited by poor bioavailability. This study optimized the sulfuric acid-catalyzed synthesis of lauric acid-esterified octacosanol (LEO) and oleic acid-esterified octacosanol (OEO) to enhance their bioactivity. Under optimized conditions (140–150 °C for 3 h), esterification rates reached 97.8% for LEO and 90.6% for OEO, with structures confirmed via gas chromatography–mass spectrometry (GC-MS), nuclear magnetic resonance (NMR), and Fourier transform infrared spectrometer (FTIR). In high-fat diet-induced obese C57BL/6J mice, both esters significantly improved serum lipid profiles compared to nonesterified octacosanol, with OEO showing the strongest efficacy in reducing total cholesterol and elevating HDL-c. Furthermore, a 28-day subacute toxicological assessment in ICR mice revealed no clinical, biochemical, or hematological abnormalities, indicating a favorable preliminary safety profile for OEO. These results suggest that OEO is a promising functional ingredient for mitigating hyperlipidemia and cardiovascular disease risk, offering improved application potential in dietary supplements.