title: Cycloartane-type triterpenes from Euphorbia fischeriana stimulate  human CYP3A4 promoter activity.
abstract: A chemical study of the roots of Euphorbia fischeriana resulted in the isolation of seven triterpenes (1-7), including two new compounds: (24R,S)-3β-24,31-epoxy-24-methylcycloartane (1) and (24R,S)-3β,31-dihydroxy-24-methoxy-24-methylcycloartane (2). Their structures were elucidated through extensive spectroscopic analyses. Cycloartanes 1-4 showed significant human CYP3A4 promoter activity through a series of luciferase reporter assays. Of these compounds, 3 and 4 activated the pregnane X receptor (PXR) and induced CYP3A4 mRNA expression in human primary hepatocytes. However, despite showing the most potent human CYP3A4 promoter activity via a PXR-independent pathway, 2 did not affect CYP3A4 mRNA expression in human primary hepatocytes. This difference is correlated to substitutions in C-24 and C-25 of the cycloartane structure.
authors.forename: Xingzhu
authors.initials: X
authors.lastname: Kuang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Kanno
authors.forename: Michiru
authors.initials: M
authors.lastname: Mochizuki
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Inouye
authors.forename: Kazuo
authors.initials: K
authors.lastname: Koike
mesh_terms: D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism*; D028481:Euphorbia / Q000737:chemistry*; D006801:Humans; D008968:Molecular Conformation; D015394:Molecular Structure; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D014315:Triterpenes; C085352:cycloartane; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human