Euphjatrophanes H-L (1-5), four new jatrophane-type and one new lathyrane-type diterpenoid, were isolated from Euphorbia peplus, along with eight known diterpenoids (6-13). Their structures were established on the basis of extensive spectroscopic analysis and X-ray crystallographic experiments. All compounds were subjected to bioactivity evaluation using flow cytometry in autophagic flux assays with HM mCherry-GFP-LC3 cells, the human microglia cells which stably expressed the tandem monomeric mCherry-GFP-tagged LC3. Compounds 1-3, 5-10, and 12 significantly increase autophagic flux, and compounds 1 and 12 displayed relatively high BBB permeability, with logPe values of -4.853 and -5.017, respectively. These findings indicated that jatrophane diterpenoids could serve as a valuable source for innovative autophagy inducers.
Keywords: Euphorbia peplus; autophagy; blood–brain barrier permeation; euphjatrophane; macrocyclic diterpenoid.