Euphejolkinolide A, a new ent-abietane lactone from Euphorbia peplus L. with promising biological activity in activating the autophagy-lysosomal pathway. Issue 2 (February 2023)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Heliyon. Volume 9:Issue 2(2023)
• Publication Date: 2023-02
• Subjects: Euphorbia peplus L. -- Euphorbiaceae -- Ent-abietane diterpenoid -- Euphejolkinolide A -- Autophagy-lysosomal pathway; Research -- Periodicals; Medical sciences -- Periodicals; Natural history -- Periodicals; Social sciences -- Periodicals; Earth sciences -- Periodicals; Physical sciences -- Periodicals; 507.2
• DOI: 10.1016/j.heliyon.2023.e13691
• Languages: English
• ISSNs: 2405-8440

Abstract

Abstract: 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 spectroscopic 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 upregulating 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 relationships (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. Graphical abstract: Image 1 Highlights: One undescribed ent -Abietane lactone was obtained from Euphorbia peplus L. The mCherry-GFP-LC3 protein was combined with flow cytometry analysis to directly reflect the strength of autophagic flux. Compound 1 activates the autophagy-lysosome system mediated by TFEB (transcription factor EB). Carbonyl at C-7 in compound 1 as a nucleophilic group might be a key active group. Abstract : Euphorbia peplus L.; Euphorbiaceae ; ent -abietane diterpenoid; Euphejolkinolide A; autophagy-lysosomal pathway.