Identification of New Polyacetylenes from Dendropanax morbifera with PPAR-α Activity Study

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.

AMP-activated protein kinase; Dendropanax morbifera Leveille; Peroxisome proliferator-activated receptor; cathepsin S; polyacetylene.