Phenolic Compounds with PCSK9 Secretion Inhibitory Activities from the Fruits of Liriope spicata

Bioactivity-guided isolation of the fresh fruits of Liriope spicata afforded two new megastigmane glucosides (1 and 2), and one new depside (3), together with 24 known compounds (4-27). The structures of all compounds were elucidated by extensive analysis of their UV, HR-MS, NMR spectroscopic data, ECD calculations, gauge-including atomic orbital (GIAO) NMR calculations. Among the isolated compounds, (+)-platyphyllarin A (5) and (3S)-3,5,4'-trihydroxy-7-methoxy-6-methylhomoisoflavanone (8) showed potent effects in reducing PCSK9 secretion, accompanied by a decrease in PCSK9 expression at both transcriptional and protein levels and enhanced uptake of 1,1'-dioctadecyl-3,3,3,3'-tetramethylindocarbocyanine perchlorate-labeled low-density lipoprotein (DiI-LDL). Notably, compounds 5 and 8 also attenuated atorvastatin-induced PCSK9 upregulation, highlighting their potential to complement and enhance atorvastatin-based lipid-lowering therapy.