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

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.