Li Dongxia, Li Wei, Higai Koji, Koike Kazuo
Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba, 274-8510, Japan.
J Nat Med. 2014 Apr;68(2):427-31. doi: 10.1007/s11418-013-0804-x. Epub 2013 Oct 6.
Protein tyrosine phosphatase 1B (PTP1B) is a non-transmembrane protein tyrosine phosphatase, and has received much attention as a molecular target for the treatment of insulin resistance diseases because of its critical roles in negatively regulating insulin- and leptin-signaling cascades. Six ursane-type triterpenes, 3β-acetoxy-urs-12-ene-28-oic acid (1), pomolic acid-3β-acetate (2), pomolic acid (3), ursolaldehyde (4), euscaphic acid (5) and 3β-acetoxy-urs-11-en-28,13-olide (6), and a lupane-type triterpene, betulinic acid (7), from the fruits of Sorbus pohuashanensis, exhibited significant PTP1B inhibitory activity, with IC50 values ranging from 3.5 to 54.8 μM. Kinetics analyses revealed that compounds 2, 3, and 7 are non-competitive PTP1B inhibitors, and compounds 1 and 6 are mixed-type PTP1B inhibitors.
蛋白酪氨酸磷酸酶1B（PTP1B）是一种非跨膜蛋白酪氨酸磷酸酶，因其在负向调节胰岛素和瘦素信号级联反应中的关键作用，作为治疗胰岛素抵抗疾病的分子靶点备受关注。从花楸果实中分离得到的6种乌苏烷型三萜化合物，3β-乙酰氧基-乌苏-12-烯-28-酸（1）、坡模酸-3β-乙酸酯（2）、坡模酸（3）、熊果醛（4）、野鸦椿酸（5）和3β-乙酰氧基-乌苏-11-烯-28,13-内酯（6），以及1种羽扇豆烷型三萜化合物，桦木酸（7），表现出显著的PTP1B抑制活性，IC50值在3.5至54.8μM之间。动力学分析表明，化合物2、3和7是非竞争性PTP1B抑制剂，化合物1和6是混合型PTP1B抑制剂。
