Euphejolkinolide A, a new ent-abietane lactone from Euphorbia peplus L. with promising biological activity in activating the autophagy-lysosomal pathway
Autor: | Xiaoqian Ran, Qing-Yun Lu, Ying-Yao Li, Xue-Xue Pu, Yarong Guo, Ming-Rui Yuan, Shi-Peng Guan, Mao Sun, Lijin Jiao, Yong-Gang Yao, Ying-Tong Di, Xiao-Jiang Hao, Rongcan Luo |
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Jazyk: | angličtina |
Rok vydání: | 2023 |
Předmět: | |
Zdroj: | Heliyon, Vol 9, Iss 2, Pp e13691- (2023) |
Druh dokumentu: | article |
ISSN: | 2405-8440 16581148 |
DOI: | 10.1016/j.heliyon.2023.e13691 |
Popis: | 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. |
Databáze: | Directory of Open Access Journals |
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