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Discovery of myrsinane diterpenoids from Euphorbia prolifera as a new type of anti-liver fibrosis agents that inhibit PI3K-AKT signaling pathway

GSE314666 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2025/12/27 Platform GPL23227
Summary
Liver fibrosis represents an unmet clinical need. Building on the high screening hit rate of Euphorbiaceae diterpenoids in our previous anti-fibrotic campaigns, we constructed a library of 29 myrsinane diterpenoids from the roots of Euphorbia prolifera in the current study. This collection features three skeletal subtypes and includes 13 new compounds, euphpronoids A-M (1-13), whose structures were elucidated by comprehensive spectroscopic analyses, ECD calculations, chemical correlation, and single-crystal X-ray diffraction. Anti-liver fibrosis screening of this library in TGF-β1-stimulated LX-2 cells revealed ten compounds that significantly suppressed fibronectin (FN) expression. The most active hit, compound 11, dose-dependently reduced the protein levels of FN, α-smooth muscle actin, and collagen I. Mechanistic studies indicated that 11 exerts its anti-fibrotic effect by inhibiting the PI3K-AKT signaling pathway. These findings underscore the potential of the myrsinane scaffold as a promising structural motif for anti-liver fibrosis drug development.
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Also filed as BioProject PRJNA1392429 and SRA study SRP657239. Searching any of these in the dataset finder brings you back here.

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