Macrocyclic diterpenoids from the seeds of Euphorbia peplus with potential activity in inducing lysosomal biogenesis.

• Five new diterpenoids were isolated from the seeds of Euphorbia peplus. • Compounds 1 – 3 feature a very rare euphoperfoliane 5/11/5-tricyclic skeleton. • Compounds 1 & 3 can significantly induce lysosomal biogenesis by activation of TFEB. The first phytochemical investigation of the seeds of Euphorbia peplus led to the isolation and characterization of five new (1 – 5), named euphopepluanones A–E, and five known diterpenoids (6 – 10). Their structures were established by extensive spectroscopic analysis and X-ray crystallographic experiments. Euphopepluanones A–E (1 – 3) feature a very rare 5/11/5-tricyclic skeleton, and euphopepluanones D–E (4 – 5) represent the first report of lathyrane type diterpenoids found in E. peplus. The new compounds 1 – 5 were assessed for their activities to induce lysosomal biogenesis through LysoTracker Red staining, in which compounds 1 and 3 could significantly induce lysosomal biogenesis. In addition, compounds 1 and 3 could promote the nuclear translocation of TFEB, a master transcriptional factor of lysosomal genes, indicating that compounds 1 and 3 induced lysosomal biogenesis through activation of TFEB. [ABSTRACT FROM AUTHOR]