Chemical constituents from Morus alba with proprotein convertase subtilisin/kexin type 9 expression and secretion inhibitory activity.

Six new flavanones, including sanggenol W (1), morusalnol D-F (2-4) and neovanone A and B (5 and6), and fourteen known compounds were isolated from the methanol extract of the dried root bark of Morus alba using various column chromatographic methods. Their structures were elucidated using spectroscopic methods. The isolated compounds were tested in vitro for LDLR, PCSK9 and IDOL mRNA regulatory activity, and it was found that betulinic acid (13) showed the most potent effect on downregulation of PCSK9 and upregulation of LDLR at both mRNA and protein levels, showing comparable results to berberine, the positive control. In addition, betulinic acid (13) inhibited PCSK9 secretion, indicating its role as a future PCSK9 synthesis inhibitor.