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.