Jatrophane Diterpenoids from Euphorbia peplus Linn. as Activators of Autophagy and Inhibitors of Tau Pathology

Ten jatrophane diterpenoids were isolated from the whole plant Euphorbia peplus Linn. including seven new ones, named euphjatrophanes A-G (labeled compounds 1, 2, 4–8). Their structures were elucidated with a combination of spectroscopic and single-crystal X-ray crystallography, enabling the identification of compounds 3, 9, and 10 as the previously published euphpepluones G, K, and L, respectively. All compounds were evaluated for their bioactivity with flow cytometry in assays of autophagic flux in HM Cherry-GFP-LC3 (human microglia cells stably expressing the tandem monomeric mCherry-GFP-tagged LC3) cells. Euphpepluone K (9) significantly activated autophagic flux, an effect that was verified with confocal analysis. Moreover, cellular assays showed that euphpepluone K (9) induced autophagy and inhibited Tau pathology.