School of Life Science and Biotechnology and Center for Human Interface Nano Technology, Sungkyunkwan University, Gyeonggi-do, Korea.
Planta Med. 2012 Feb;78(3):233-6. doi: 10.1055/s-0031-1280385. Epub 2011 Nov 22.
Most cosmetic and therapeutic applications of Clostridium botulinum neurotoxin (BoNT) are related to muscle paralysis caused by the blocking of neurotransmitter release at the neuromuscular junction. BoNT specifically cleaves SNARE proteins at the nerve terminal and impairs neuroexocytosis. Recently, we have shown that several polyphenols inhibit neurotransmitter release from neuronal PC12 cells by interfering with SNARE complex formation. Based on our previous result, we report here that myricetin, delphinidin, and cyanidin indeed paralyze muscle by inhibiting acetylcholine release at the neuromuscular junction. While the effect of myricetin on muscle paralysis was modest compared to BoNT/A, myricetin exhibited a shorter response time than BoNT/A. Intraperitoneally-injected myricetin at an extreme dose of 1000 mg/kg did not induce death of mice, alleviating the safety issue. Thus, these polyphenols might be useful in treating various human hypersecretion diseases for which BoNT/A has been the only option of choice.
大多数肉毒梭菌神经毒素 (BoNT) 的美容和治疗应用都与肌肉麻痹有关，这种麻痹是由于在运动终板处阻断神经递质释放引起的。BoNT 特异性地在神经末梢切割 SNARE 蛋白，从而损害神经递质的胞吐作用。最近，我们已经表明，几种多酚通过干扰 SNARE 复合物的形成来抑制神经元 PC12 细胞中神经递质的释放。基于我们之前的结果，我们在这里报告说，杨梅素、矢车菊素和飞燕草素确实通过抑制运动终板处的乙酰胆碱释放而使肌肉麻痹。与 BoNT/A 相比，杨梅素对肌肉麻痹的作用较小，但杨梅素的反应时间比 BoNT/A 短。腹腔内注射 1000mg/kg 的杨梅素不会导致小鼠死亡，缓解了安全性问题。因此，这些多酚类化合物可能对治疗各种人类过度分泌疾病有用，而 BoNT/A 一直是唯一的选择。
