Jin WenYi, Cai Xing Fu, Na MinKyun, Lee Jung Joon, Bae KiHwan
College of Pharmacy, Chungnam National University, Daejeon, Korea.
Arch Pharm Res. 2007 Apr;30(4):412-8. doi: 10.1007/BF02980213.
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 IC50 values of 11.2 microM and 12.3 microM, respectively. These two compounds had no significant cytotoxicity to the AGS cells at the effective concentration for the inhibition of HIF-1 activation.
采用体外低氧诱导因子-1（HIF-1）检测法，对糙皮桦（桦木科）茎皮甲醇提取物的乙酸乙酯可溶部分进行生物测定引导的分级分离和纯化，从中分离出4种三萜类化合物（1-4）和6种二芳基庚烷类化合物（5-10）。通过与文献中的物理化学和光谱数据进行比较确定了它们的结构。使用AGS细胞中HIF-1α介导的报告基因检测法，研究了这些化合物对低氧诱导的HIF-1激活的影响。其中，两种二芳基庚烷类化合物，2-氧杂三环[13.2.2.13,7]二十碳-3,5,7(20),15,17,18-六烯-10-16-二醇（6）和2-氧杂三环[13.2.2.13,7]二十碳-3,5,7-(20),15,17,18-六烯-10-酮（7），对HIF-1激活具有剂量依赖性抑制作用，IC50值分别为11.2 microM和12.3 microM。在抑制HIF-1激活的有效浓度下，这两种化合物对AGS细胞无明显细胞毒性。
