Structurally Diverse Rhamnofolane, Tigliane, and Daphnane Diterpenoids from Euphorbia wallichii as Anti-Liver Fibrosis Agents

Twelve new diterpenoids, euphorwallnoids A−L (1−12), including 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. Their structures were elucidated by a combination of spectroscopic, computational, chemical, and single-crystal X-ray diffractions means. Euphorwallnoid A (1) is a rhamnofolane featuring an unusual 5/7/6/5-tetracyclic scaffold, while 2−5 and 6−8 represent a rare class of 4-deoxygenated rhamnofolanes and 13-deoxygenated tiglianes, respectively. Notably, 1 was identified as a promising anti-liver fibrosis agent that could inhibit the expressions of fibronectin, α-smooth muscle actin, and collagen I in TGF-β1-stimulated LX-2 cells at micromolar level.