Euphejolkinolide A, a new ent-abietane lactone from Euphorbia peplus L. with promising biological activity in activating the autophagy-lysosomal pathway

A new ent-abietane diterpenoid, named Euphejolkinolide A (1), was isolated from the whole plant of Euphorbia peplus L. Its structure, including absolute configurations, was determined by spec-troscopic analyses and was corroborated by single-crystal X-ray diffraction analysis. This new compound was assessed for its activity to induce lysosome biogenesis through Lyso-Tracker Red staining, in which compound 1 could significantly induce lysosome biogenesis. In addition, quantitative real-time PCR (qRT-PCR) analysis demonstrated a direct correlation between the observed lysosome biogenesis and the transcriptional activation of the lysosomal genes after treatment with the compound 1. Moreover, compound 1 promoted autophagic flux by upregu-lating LC3-II and downregulating SQSTM1 in both human microglia cells and U251 cells, which is required for cellular homeostasis. Further results suggested 1 induced lysosome biogenesis and autophagy which was mediated by TFEB (transcription factor EB). The structure activity re-lationships (SAR) analysis suggested that the carbony1 at C-7 in 1 might be a key active group. Overall, the current data suggested that 1 could be a potential compound for lysosome disorder therapy by induction of autophagy.

Automated summary

A new ent-abietane diterpenoid, Euphejolkinolide A (1), was isolated from Euphorbia peplus L. and its structure and configurations were confirmed by spectroscopic analyses and single-crystal X-ray diffraction analysis. It was found that compound 1 could significantly induce lysosome biogenesis and promote autophagic flux, which is required for cellular homeostasis. The study also suggested that the carbony1 at C-7 in compound 1 might be a key active group. Overall, compound 1 shows potential for lysosome disorder therapy by inducing autophagy.