Cure of experimental botulism and antibotulismic effect of toosendanin  

作　　者：Yu-liangSHI Zhong-fengWANG 

机构地区：[1]Keylaboratory,ofNeurobiology,ShanghaiInstitutesforBiologicalSciences,ChineseAcademyofScience,Shanghai200031,China

出　　处：《Acta Pharmacologica Sinica》2004年第6期839-848,共10页中国药理学报（英文版）

基　　金：Project supported by the National Basic Research Program ofChina(G1999054000);NationalNatural Science Foundation ofChina (30170302; 39870249); and Basic Research Program ofShanghai(02JC14011).

摘　　要：Botulinum neurotoxins (BoNTs), a group of bacterial proteins that comprise a light chain disulfide linked a heavy chain, are the most lethal biotoxins known to mankind. By inhibiting neurotransmitter release, BoNTs cause severe neuroparalytic disease, botulism. A series of important findings in the past 10 years which displayed the molecular targets of BoNTs and hence proposed a four-step action mechanism to explain BoNT intoxication greatly advanced the study of antibotulismic drug. In this article, we reviewed these progresses and anti-botulismic compounds found in recent years. These compounds function due to their facilitation on neurotransmitter release or to their interference on the binding, internalization, translocation, and endopeptidase activity of the toxins. Toosendanin is a triterpenoid derivative extracted from a digestive tract-parasiticide in Chinese traditional medicine. Chinese scientists have found that the compound is a selective prejunctional blocker. In spite of sharing some similar action with BoNT, toosendanin can protect botulism animals that have been administrated with lethal doses of BoNT/A or BoNT/B for several hours from death and make them restore normal activity. The neuromuscular junction preparations isolated from the rats that have been injected with toosendanin tolerate BoNT/A challenge. Toosendanin seems to have no effect on endopeptidase activity of BoNT, but blocks the toxin approach to its enzymatic substrate.Botulinum neurotoxins (BoNTs), a group of bacterial proteins that comprise a light chain disulfide linked a heavy chain, are the most lethal biotoxins known to mankind. By inhibiting neurotransmitter release, BoNTs cause severe neuroparalytic disease, botulism. A series of important findings in the past 10 years which displayed the molecular targets of BoNTs and hence proposed a four-step action mechanism to explain BoNT intoxication greatly advanced the study of antibotulismic drug. In this article, we reviewed these progresses and anti-botulismic compounds found in recent years. These compounds function due to their facilitation on neurotransmitter release or to their interference on the binding, internalization, translocation, and endopeptidase activity of the toxins. Toosendanin is a triterpenoid derivative extracted from a digestive tract-parasiticide in Chinese traditional medicine. Chinese scientists have found that the compound is a selective prejunctional blocker. In spite of sharing some similar action with BoNT, toosendanin can protect botulism animals that have been administrated with lethal doses of BoNT/A or BoNT/B for several hours from death and make them restore normal activity. The neuromuscular junction preparations isolated from the rats that have been injected with toosendanin tolerate BoNT/A challenge. Toosendanin seems to have no effect on endopeptidase activity of BoNT, but blocks the toxin approach to its enzymatic substrate.

关 键 词：TOOSENDANIN botulinum toxins BOTULISM synaptic transmission NEUROTRANSMITTER TRITERPENE Chinese traditional medicine 

分 类 号：R595.7[医药卫生—内科学]