Structurally diverse rhamnofolane, tigliane, and daphnane diterpenoids from Euphorbia wallichii as anti-liver fibrosis agents

Abstract

Twelve new diterpenoids, euphorwallnoids A−L (1−12), comprising five rhamnofolanes (1−5), five tiglianes (6−10), and two daphnanes (11 and 12), along with six known analogues (13−18), were isolated from the whole plants of Euphorbia wallichii (E. wallichii). Their structures were determined using spectroscopic analysis, computational methods, chemical derivatization, and single-crystal X-ray diffraction. Euphorwallnoid A (1) features an unusual 5/7/6/5-tetracyclic scaffold, whereas 2−5 represent a rare subclass of 4-deoxygenated rhamnofolanes and 6−8 constitute 13-deoxygenated tiglianes. Notably, compound 1 demonstrated promising anti-liver fibrosis activity by significantly inhibiting the expression of fibronectin (FN), α-smooth muscle actin (α-SMA), and collagen I in transforming growth factor β1 (TGF-β1)-stimulated LX-2 cells at micromolar concentrations.

Keywords

Euphorbia wallichii / Diterpenoids / Rhamnofolanes / Tiglianes / Daphnanes / Liver fibrosis

Funding

This work was supported by the National Natural Science Foundation of China (Nos. 82404454, 22407144, and 82304322), the China Postdoctoral Science Foundation (No. 2024M753800),the Postdoctoral Fellowship Program of CPSF (No. GZC20242113), and the Open Program of Shenzhen Bay Laboratory (No. SZBL2021080601007).

Supporting information

Supporting information is available free of charge at: ¹H−¹H COSY and HMBC correlations of 3−5, 7−10, and 12; Key NOESY correlations of 4−8 and 10−12; NMR calculations for 1; ECD calculations for 2, 3, 9, 11, and 12; NMR, HR-ESI-MS, and IR spectra of 1−12; 1D NMR spectra of 13−18.

Declaration of competing interest

The authors declare no competing financial interest.

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