Euphejolkinolide A, a new ent-abietane lactone from Euphorbia peplus L. with promising biological activity in activating the autophagy-lysosomal pathway
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
Affiliations
Xiaoqian Ran
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
Qing-Yun Lu
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China
Ying-Yao Li
College of Life Sciences, Yunnan University, Kunming, 650091, China
Xue-Xue Pu
College of Traditional Medicine, Yunnan University of Chinese Medicine, Kunming, 650500, China
Yarong Guo
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; School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China
Ming-Rui Yuan
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China
Shi-Peng Guan
College of Traditional Medicine, Yunnan University of Chinese Medicine, Kunming, 650500, China
Mao Sun
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China
Lijin Jiao
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
Yong-Gang Yao
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; CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China
Ying-Tong Di
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, 650204, China; College of Traditional Medicine, Yunnan University of Chinese Medicine, Kunming, 650500, China; Corresponding author. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.
Xiao-Jiang Hao
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China; Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming, Yunnan, 650201, China; Guizhou Chemical Drug Research and Development Engineering Technical Center, Guizhou Medicinal University, Guiyang, 550004, China
Rongcan Luo
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; Corresponding author. 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.
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.
