Tong Jia, Lu Jincai, Zhang Na, Chi Haidong, Yamashita Koichi, Manabe Masanobu, Kodama Hiroyuki
Department of Anesthesiology and Critical Care Medicine, Kochi Medical School, Nankoku Shi, Kochi, Japan.
Planta Med. 2009 Jun;75(8):814-22. doi: 10.1055/s-0029-1185440. Epub 2009 Mar 13.
Taxol has been widely used as an anticancer drug for ovarian, breast, lung and prostate cancer. Some kinds of Taxus plants are widely distributed in the Northeast Asia region. We have isolated seven tricyclic diterpenoids, taxinine, taxagifine, 5-O-cinnamoyltaxacin I triacetate, 5-decinnamoyltaxinine J, 5-cinnamoyl-9-acetyltaxicin I, taxacin and taxol from the needles of Taxus media var. Hicksii, and investigated their effects on stimulus-induced superoxide generation and translocation of cytosolic compounds to the cell membrane in human neutrophils. Six tricyclic diterpenoids used in this experiment suppressed the superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) and arachidonic acid (AA) in a concentration-dependent manner. Taxinine significantly suppressed the superoxide generation induced by phorbol 12-myristate 13-acetate (PMA). The compounds also suppressed fMLP- and AA-induced tyrosyl or PMA-induced serine/threonine phosphorylation, and translocation of cytosolic compounds, p47 (phox), p67 (phox) and Rac to the cell membrane in parallel with the suppression of the stimulus-induced superoxide generation.
紫杉醇已被广泛用作治疗卵巢癌、乳腺癌、肺癌和前列腺癌的抗癌药物。某些种类的红豆杉植物在东北亚地区广泛分布。我们从曼地亚红豆杉（Taxus media var. Hicksii）的针叶中分离出了七种三环二萜类化合物，即紫杉宁、紫杉吉酚、5-O-肉桂酰紫杉素I三乙酸酯、5-去肉桂酰紫杉宁J、5-肉桂酰-9-乙酰紫杉素I、紫杉素和紫杉醇，并研究了它们对人中性粒细胞中刺激诱导的超氧化物生成以及胞质化合物向细胞膜转位的影响。本实验中使用的六种三环二萜类化合物以浓度依赖的方式抑制了由N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）和花生四烯酸（AA）诱导的超氧化物生成。紫杉宁显著抑制了佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）诱导的超氧化物生成。这些化合物还抑制了fMLP和AA诱导的酪氨酸磷酸化或PMA诱导的丝氨酸/苏氨酸磷酸化，以及胞质化合物p47（phox）、p67（phox）和Rac向细胞膜的转位，同时抑制了刺激诱导的超氧化物生成。
