Salamon Nora, Gurgui Cristian, Leistner Eckhard, Drewke Christel
Institute of Pharmaceutical Biology, University of Bonn, 53115 Bonn, Germany.
Planta Med. 2009 May;75(6):563-7. doi: 10.1055/s-0029-1185482. Epub 2009 Mar 13.
The pharmacological effects of leaf extracts (EGb 761) from Ginkgo biloba L. are attributed to ginkgolides, bilobalide and biflavonoids. However, besides these beneficial attributes, ginkgotoxin, a B(6) antivitamin which may cause epileptic convulsions, other severe neuronal disorders and even death, is also found in Ginkgo leaves and leaf-derived remedies. Because of its structural similarity to the B(6) vitamers, an interaction of ginkgotoxin with enzymes involved in the vitamin B(6)-dependent metabolism of the human brain is possible. This led us to investigate how the neurotoxic ginkgotoxin acts in the brain. To this end the gene coding for the human pyridoxine 5'-phosphate oxidase was heterologously overexpressed in E. COLI and the homogeneous enzyme was characterized. The investigation showed that the enzyme is inhibited in vitro by the synthetic vitamin B(6) derivative 4'-deoxypyridoxine 5'-phosphate but not by ginkgotoxin or its 5'-phosphate.
银杏叶提取物（EGb 761）的药理作用归因于银杏内酯、白果内酯和双黄酮类化合物。然而，除了这些有益特性外，银杏叶和叶源药物中还发现了银杏毒素，一种可能导致癫痫惊厥、其他严重神经紊乱甚至死亡的维生素B6抗维生素。由于其与维生素B6异构体的结构相似性，银杏毒素有可能与人脑维生素B6依赖性代谢中涉及的酶发生相互作用。这促使我们研究神经毒性银杏毒素在大脑中的作用方式。为此，编码人吡哆醇5'-磷酸氧化酶的基因在大肠杆菌中异源过表达，并对纯化的酶进行了表征。研究表明，该酶在体外被合成维生素B6衍生物4'-脱氧吡哆醇5'-磷酸抑制，但不受银杏毒素或其5'-磷酸抑制。
