Dendropanax morbifera Leveille is a traditional medicine used to treat migraine headache and dysmenorrhea. In this study, three polyacetylenes, methyl (10E,9R,16R)-16-acetoxy-9-hydroxyoctadeca-10,17-dien-12,14-diynoate (1), methyl (10E,9R,16S)-9,16-dihydroxyoctadeca-10-en-12,14-diynoate (2), and methyl (10Z,9R,16S)-9,16-dihydroxyoctadeca-10,17-dien-12,14-diynoate (3), were isolated from the aerial parts of D. morbifera, together with seven known compounds (4–10). Importantly, the isolates (6 and 8) were found in the family Araliaceae for the first time in this study. Compounds 1−10 were evaluated for their binding affinity to AMPK and CTSS receptors using in silico docking simulations. Only compound 7 increased the protein expression levels of PPAR-α, Sirt1, and AMPK when administered to HepG2 cells as a PPAR-α agonist. On the other hand, 7 did not produce any significant reduction in CTSS activity. This study could pave the way for the discovery of novel treatments from D. morbifera targeting PPAR-α and AMPK.
