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

作者：Ran, Xiaoqian; Lu, Qing-Yun; Li, Ying-Yao; Pu, Xue-Xue; Guo, Yarong; Yuan, Ming-Rui; Guan, Shi-Peng; Sun, Mao; Jiao, Lijin; Yao, Yong-Gang; Di, Ying-Tong^*; Hao, Xiao-Jiang; Luo, Rongcan^*

来源：Heliyon, 2023, 9(2): e13691.

DOI：10.1016/j.heliyon.2023.e13691

• Euphorbia peplus L
• Euphorbiaceae
• Ent-abietane diterpenoid
• Euphejolkinolide A
• 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.

• 单位
  中国科学院; 云南大学; 中国科学院研究生院