Discovery of Ingenane Diterpenoids from Euphorbia hylonoma as Antiadipogenic Agents.

Thirteen new Euphorbia diterpenoids, euphylonanes A-M ( 1 - 13 ), and eight known ones were isolated from the whole plants of Euphorbia hylonoma . Compounds 1 and 2 are two rearranged ingenanes bearing a rare 6/6/7/3-fused ring system. Compound 3 represents the first example of a 9,10-epoxy tigliane, while 4 - 21 are typical ingenanes varying with substituents. Structures were elucidated using a combination of spectroscopic, computational, and chemical methods. Most ingenanes exerted a significant antiadipogenic effect in 3T3-L1 adipocytes, among which 4 was the most active with an EC 50 value of 0.60 ± 0.27 μM. Mechanistic study revealed that 4 inhibited the adipogenesis and lipogenesis in adipocytes via activation of the AMPK signaling pathway.