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目的鉴定川楝素水解及氢化还原产物的结构,并测定其对肉毒毒素的解毒效果。方法用一定比例的稀氨水水解川楝素,用氢化铝锂还原川楝素的环氧键,然后用高效液相色谱纯化各产物,用质谱、核磁共振氢谱鉴定产物结构;解毒活性测定中,小鼠用2LD50的A型肉毒毒素攻毒,腹腔注射不同剂量的川楝素水解及氢化产物后,4 d内观察小鼠死亡情况。结果与结论除全脱乙酰基产物外,获得2个川楝素单脱乙酰基产物及全脱乙酰基并环氧键还原的新产物,这些产物的毒性及对肉毒毒素的解毒活性降低。该工作为川楝素的体内药代产物鉴定及应用奠定了一定的基础。
Objective To identify the structure of toosendanin hydrolysis and hydrogenation reduction products, and determine the detoxification effect of botulinum toxin. Methods Toosendanin was hydrolyzed by a certain proportion of dilute aqueous ammonia and the epoxy bond of toosendanin was reduced with lithium aluminum hydride. The products were purified by high performance liquid chromatography (HPLC) and identified by mass spectrometry and 1H nuclear magnetic resonance spectroscopy. The mice were challenged with 2LD50 botulinum toxin type A. The mice were killed within 4 days after intraperitoneal injection of different doses of toosendanin and hydrogenated products. RESULTS AND CONCLUSION In addition to the all-deacetylated products, two new products of monoterretinoate and all-deacetyl-epoxy bond were obtained. The toxicity of these products and the detoxification activity of botulinum toxin were reduced. This work has laid a solid foundation for the identification and application of toosendanin in vivo.