Presegetane diterpenoids from Euphorbia sieboldiana as a new type of anti-liver fibrosis agents that inhibit TGF-β/Smad signaling pathway
| Autor: | Fang-Yu Yuan, Sheng Yin, Xu Zhang, Run-Zhu Fan, Xue-Long Yan, Qin-Feng Zhu, Yang Tian, Yi-Jing Tian, Gui-Hua Tang, Dong Huang, Yan Lin, Lu Gan, Shen Li |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Liver Cirrhosis
Liver fibrosis Smad Proteins SMAD Biochemistry Euphorbia Transforming Growth Factor beta Fibrosis Drug Discovery medicine Humans Structural motif Molecular Biology Cells Cultured biology Plant Extracts Chemistry Organic Chemistry Plant Components Aerial medicine.disease Molecular biology Terpenoid Fibronectin Drug development biology.protein Diterpenes Signal transduction Signal Transduction |
| Zdroj: | Bioorganic Chemistry. 114:105222 |
| ISSN: | 0045-2068 |
| DOI: | 10.1016/j.bioorg.2021.105222 |
| Popis: | Seven new diterpenoids, eupholenes A-G (1-7), including two presegetanes (1 and 2), four jatrophanes (3-6), and one paraliane (7), along with 19 known analogues (8-26) were obtained by anti-liver fibrosis bioassay-guided isolation of Euphorbia sieboldiana. Their structures were elucidated by extensive spectroscopic data analyses, chemical methods, ECD calculations, and single-crystal X-ray diffractions. Euphorbesulin A (10), a presegetane diterpenoid (5/9/5 ring system), was identified as a promising anti-liver fibrosis agent that could inhibit the expressions of fibronectin (FN), α-smooth muscle actin (α-SMA), and collagen I in TGF-β1-stimulated LX-2 cells at a micromolar level. Mechanistic study revealed that 10 suppressed liver fibrosis via inhibition of TGF-β/Smad signaling pathway, and its potential target was TGF-β type I receptor. These findings suggested that presegetane diterpenoid could serve as a new type of structural motif in future anti-liver fibrosis drug development. |
| Databáze: | OpenAIRE |
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