Four new sesquiterpene lactones from Atractylodes macrocephala and their CREB agonistic activities.

One new bisesquiterpenoid, biepiasreorlid II (1), three new sesquiterpene lactones 8α-methoxy-epiasterolid (4), 3ß-acetoxyl-8-epiasterolid (5), and 3ß-acetoxyl-atractylenolide I (6), along with five known analogues (2-3 and 7-9), were obtained from rhizome of Atractylodes macrocephala Koidz. All structures were assigned on the basis of detailed spectroscopic analyses. The absolute configuration of 1 was established by the analysis of single-crystal X-ray diffraction with Ga Kα radiation, and 4-6 were elucidated by TDDFT-ECD calculations. The CREB agonistic activity was investigated in HEK293T cells using dual luciferase reporter assay. Compounds 1, 2, 5, and 7-9 exhibited strong to agonistic activities on CREB.