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.