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
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650204, China.
Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, 650204, China.
Heliyon. 2023 Feb 13;9(2):e13691. doi: 10.1016/j.heliyon.2023.e13691. eCollection 2023 Feb.
A new -abietane diterpenoid, named Euphejolkinolide A (), was isolated from the whole plant of 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 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 . Moreover, compound 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 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 might be a key active group. Overall, the current data suggested that could be a potential compound for lysosome disorder therapy by induction of autophagy.
从泽漆全草中分离得到一种新的松香烷二萜类化合物，命名为泽漆醇内酯A（）。通过光谱分析确定了其结构，包括绝对构型，并经单晶X射线衍射分析证实。通过Lyso-Tracker Red染色评估了该新化合物诱导溶酶体生物发生的活性，其中化合物可显著诱导溶酶体生物发生。此外，定量实时PCR（qRT-PCR）分析表明，在用该化合物处理后，观察到的溶酶体生物发生与溶酶体基因的转录激活之间存在直接相关性。此外，化合物在人小胶质细胞和U251细胞中均通过上调LC3-II和下调SQSTM1促进自噬通量，这是细胞稳态所必需的。进一步的结果表明，诱导的溶酶体生物发生和自噬是由转录因子EB（TFEB）介导的。结构活性关系（SAR）分析表明，中的C-7位羰基可能是关键活性基团。总体而言，目前的数据表明，通过诱导自噬，可能是一种治疗溶酶体疾病的潜在化合物。
