Alpinumisoflavone and abyssinone V 4-methylether derived from Erythrina lysistemon (Fabaceae) promote HDL-cholesterol synthesis and prevent cholesterol gallstone formation in ovariectomized rats

ObjectivesErythrina lysistemon was found to improve lipid profile in ovariectomized rats. Alpinumisoflavone (AIF) and abyssinone V 4-methylether (AME) derived from this plant induced analogous effects on lipid profile and decreased atherogenic risks. To highlight the molecular mechanism of action of these natural products, we evaluated their effects on the expression of some estrogen-sensitive genes associated with cholesterol synthesis (Esr1 and Apoa1) and cholesterol clearance (Ldlr, Scarb1 and Cyp7a1). MethodsOvariectomized rats were subcutaneously treated for three consecutive days with either compound at the daily dose of 0.1, 1 and 10mg/kg body weight (BW). Animals were sacrificed thereafter and their liver was collected. The mRNA of genes of interest was analysed by quantitative real-time polymerase chain reaction. Key findingsBoth compounds downregulated the mRNA expression of Esr1, a gene associated with cholesterogenesis and cholesterol gallstone formation. AME leaned the Apoa1/Scarb1 balance in favour of Apoa1, an effect promoting high-density lipoprotein (HDL)-cholesterol formation. It also upregulated the mRNA expression of Ldlr at 1mg/kg/BW per day (25%) and 10mg/kg/BW per day (133.17%), an effect favouring the clearance of low-density lipoprotein (LDL)-cholesterol. Both compounds may also promote the conversion of cholesterol into bile acids as they upregulated Cyp7a1mRNA expression. ConclusionAIF and AME atheroprotective effects may result from their ability to upregulate mechanisms promoting HDL-cholesterol and bile acid formation.