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.

Perforalactones D and E, two new C-20 quassinoids with potential activity to induce lysosomal biogenesis from the twigs of Harrisonia perforata (Blanco) Merr.

Two new quassinoids (1 and 2) were isolated from the twigs of Harrisonia perforata (Blanco) Merr. Perforalactone E (2) possesses an uncommon hexacyclic 1α,12α:5α,13α-dicyclo-9ßH-picrasane skeleton. Its structure was determined based on spectroscopic data and X-ray crystallography. Compounds 1 and 2 could significantly induce lysosomal biogenesis through transcriptional activation of lysosomal genes.

New Secodaphnane-Type Alkaloids with Cytotoxic Activities from Daphniphyllum angustifolium Hutch.

One new Daphniphyllum alkaloid, daphnioldhanol A (1), together with three known ones, were isolated from the stem part of Daphniphyllum angustifolium Hutch. Their structures were elucidated by spectroscopic methods and comparing with the literature data. Compound 2 is a new natural product, but known by synthesis as a racemate. Compound 1 exhibited week cytotoxic activity against Hela cell line with IC50 of 31.9 µM.