5-Methylcoumarins and acetophenone derivatives from Gerbera piloselloides with lipid-lowering activity.

Two pairs of previously unreported enantiomeric 5-methylcoumarins, gerbeloidanol O and P (1 and 2), and three undescribed acetophenone derivatives, gerbeloidanols Q-S (3-5), were isolated from Gerbera piloselloides. Additionally, six known coumarins (6-11) and four known acetophenone derivatives (12-15) were identified. The planar structures of the isolates were established by comprehensive analysis of NMR data, and the absolute configurations of the new compounds were determined by ECD calculations. To evaluate their potential lipid-lowering effects, all isolates were screened using an LDL uptake assay in HepG2 cells. At a concentration of 10 μM, 2-[(2S*)-6-acetyl-2,3-dihydro-5-hydroxybenzofuran-2-yl]prop-2-enyl-3-methylbutanoate (15) significantly enhanced LDL uptake and reduced the PCSK9 protein level in the culture medium by 53.03%. Gerbeloid J (7) and 3-(2-hydroxy-3-methyl-3-butenyl)-5-(3-methyl-2-butenyl)-4-hydroxyacetophenone (14) were also effective in increasing LDL uptake.