Triterpenoids and diarylheptanoids from alnus hirsuta inhibit HIF-1 in AGS cells

Abstract

Bioassay-guided fractionation and purification of the EtOAc soluble fraction from the MeOH extract of the stem bark of Alnus hirsuta (Betulaceae), using an in vitro HIF-1 assay, led to the isolation of four triterpenoids (1-4) and six diarylheptanoids (5-10). Their structures were determined by comparison with the physicochemical and spectroscopic data in the literature. These compounds were investigated for their effects on the hypoxia-induced HIF-1 activation using an HIF-1a mediated reporter gene assay in AGS cells. Among them, two diarylheptanoids, 2-oxatrycyclo[13.2.2.13,7]eicosa-3,5,7(20),15,17,18- hexaen-10-16-diol (6) and 2-oxatrycyclo [13.2.2.13,7]eicosa-3,5,7-(20),15,17,18- hexaen-10-one (7), inhibited HIF-1 activation dose-dependently with IC 50 values of 11.2 μM and 12.3 μ M, respectively. These two compounds had no significant cytotoxicity to the AGS cells at the effective concentration for the inhibition of HIF-1 activation.