Spirocyclic Nortriterpenoids with NGF-Potentiating Activity from the Fruits of Leonurus heterophyllus

Four new spirocyclic nortriterpenoids, lemurusoleanolide A (1), leonurusoleanolide B (2), leonurusoleanolide C (3), and leonurusoleanolide D (4), were isolated from the MeOH extract of the fruits of Leonurus heterophyllus. Compounds 1 and 2, and compounds 3 and 4, were found to exist as equilibrium mixtures of trans and cis isomers. Mixtures of 1 and 2, and 3 and 4, significantly enhanced the neurite outgrowth of nerve growth factor-treated PC12 cells at concentrations ranging from 1 to 30 mu M. Compound 8 was also found to have a neurite outgrowth-promoting effect at concentrations of 1 and 10 mu M. The structure-activity relationship of these compounds is discussed.