Cure of experimental botulism and antibotulismic effect of toosendanin.
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.
Shi
Yu-Liang
YL
Key laboratory of Neurobiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai 200031, China. ylshi@server.shcnc.ac.cn
Wang
Zhong-Feng
ZF
D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077770:Amifampridine; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D001906:Botulism / Q000188:drug therapy*; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D031585:Melia / Q000737:chemistry; D018377:Neurotransmitter Agents / Q000378:metabolism; D010946:Plants, Medicinal / Q000737:chemistry; D026902:Potassium Channel Blockers / Q000627:therapeutic use; D014315:Triterpenes
D015761:4-Aminopyridine; D000077770:Amifampridine; D001905:Botulinum Toxins; D004365:Drugs, Chinese Herbal; D018377:Neurotransmitter Agents; D026902:Potassium Channel Blockers; C036454:toosendanin; D014315:Triterpenes