The Antibotulismic Mechanism Of Toosendanin

Botulinum neurotoxins (BoNTs) are the most lethal biotoxins known to mankind. Seven distinct serotypes have been identified and designated type A to G. The principal targets are the cholinergic nerve ending, where by cleavage of soluble NSF accessory protein receptor (SNARE), which are critical to neurotransmitter release, results in neuromuscular blockade, and leads the animal to death by breath failure. Toosendanin (TSN, C30H38O11, FW 574), a triterpenoid derivative isolated from the bark of Melia toosendan Sieb et Zucc, has been used as an anthelmintic vermifuge against ascaris in China. It was demonstrated that toosendanin was a selective presynaptic blocker, which blocked the neurotransmitter release both in peripheral and central nervous system. And it has been reported to be an effective cure of experimental botulism. This study was designed to explore its antibotulismic mechanism by western blotting method. The results showed that 1) TSN saved mice injected with lethal doses of BoNT/A from death. 2) TSN-incubation did not change the electrophoresis pattern and the amounts of SNAP-25, syntaxin and synaptobrevin/VAMP in rat cerebral synaptosomes, but made the synaptosomes completely resistant to BoNT/A-mediated cleavage of SNAP-25. 3) TSN-incubation did not inhibit the directly cleavage of SNAP-25 on synaptosomal membrane fraction by the light chain of BoNT/A.