Macrocyclic Diterpenoids from Euphorbia peplus Possessing Activity Towards Autophagic Flux

Euphjatrophanes H-L ( - ), four new jatrophane-type and one new lathyrane-type diterpenoid, were isolated from , along with eight known diterpenoids ( - ). 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 - , - , and significantly increase autophagic flux, and compounds and displayed relatively high BBB permeability, with log values of -4.853 and -5.017, respectively. These findings indicated that jatrophane diterpenoids could serve as a valuable source for innovative autophagy inducers.