石杉碱甲与石杉碱乙组合对乙酰胆碱酯酶抑制活性的增效减毒作用  

Synergism and attenuation effect of anti-acetylcholinesterase activity of compositions comprising compounded huperzine A and huperzine B

作　　者：谢家骏[1] 谢德隆[2] 

机构地区：[1]上海中医药大学,上海201203 [2]上海中药创新研究中心,上海201203

出　　处：《中国新药与临床杂志》2014年第2期142-145,共4页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家科技重大专项课题(2011ZX09301-009)

摘　　要：目的观察石杉碱甲(Hup A)与石杉碱乙(Hup B)不同比例组合物抗乙酰胆碱酯酶(AChE)活性及安全性的影响。方法采用比色法检测Hup A与Hup B不同比例组合物对大鼠全血AchE活性及对小鼠急性毒性的影响。结果Hup A与Hup B以2:1、1:1、1:2、1:4比例组合物对大鼠全血AchE活性均具有明显的抑制作用,其IC_(50)分别为8.04×10^(-6)g·L^(-1)、8.40×10^(-6)g·L^(-1)、9.74×10^(-6)g·L^(-1)和13.12×10^(-6)g·L^(-1),其中Hup A用量分别为5.36×10^(-6)g·L^(-1)、4.20×10^(-6)g·L^(-1)、3.25×10^(-6)g·L^(-1)和2.62×10^(-6)g·L^(-1),而对照品Hup A和Hup B的IC_(50)分别为4.82×10^(-6)g·L^(-1)和854.65×10^(-6)g·L^(-1);以2:1、1:1、1:2、1:4比例组合物灌胃给小鼠,其LD_(50)的95%可信限分别为(9.23±1.95)mg·kg^(-1)、(13.76±2.98)mg·kg^(-1)、(20.33±4.29)mg·kg^(-1)和>40.00 mg·kg^(-1),其中Hup A用量分别为6.09 mg·kg^(-1)、6.74 mg·kg^(-1)、6.57 mg·kg^(-1)和8.00 mg·kg^(-1),而对照品Hup A和Hup B的LD_(50)的95%可信限分别为(6.03±1.46)mg·kg^(-1)和>40.00 mg·kg^(-1)。结论在Hup A与Hup B组合物中,当成分Hup A/Hup B≤1时,随着Hup B比例提高,Hup A活性增强,毒性下降,显示有一定的减毒增效作用。AIM To investigate the inhibitory effects of the compositions with different proportions of huperzine A （Hup A） and huperzine B （Hup B） on acetylcholinesterase activity in vitro and evaluate their toxicity in vivo. METHODS Rat blood was treated with different compositions containing several proportions of Hup A and Hup B. The acetylcholinesterase activities in blood were detected by colorimetric assay and the acute toxicity was examined in mice. RESULTS The activities of acetylcholinestorase in blood were obviously inhibited by different compositions, in which the proportions of Hup A and Hup B were 2 ： 1, 1 ： 1, 1 ： 2, 1 ： 4, respectively. The IC50 values were 8.04×10^-6g·L^-1、8.40×10^-6g·L^-1、9.74 and 10^-6g·L^-1 respectively, and among them the dosages of Hup A were 5.36×10^-6g·L^-1、4.20×10^-6g·L^-1、3.25×10^-6g·L^-1 respectively. The IC50 values of the control Hup A and Hup B were 4.82×10^-6,854.65×10^-6g·L^-1. The compositions containing the same proportions of Hup A and Hup B （2 ： 1, 1 ： 1, 1 ： 2, 1 ： 4） were given intragastrically in mice. The LD50 values （LD50 - 95% confidence limit） were （9.23±1.95）, （13.76 ±2.98）, （20.33 ± 4.29） and 〉 40.00 mg·kg^-1 respectively, and among them the dosages of Hup A were 6.15, 6.88, 6.78 and 〉 8.00 mg·kg^-1 respectively. The LD50 values of the control Hup A and Hup B were （6.03 ± 1.46） and 〉 40.00 mg·kg^-1 respectively. CONCLUSION Hup B along with Hup A exhibits an increased efficacy and an attenuation of toxicity in the compositions comprising compounded huperzine A and Huperzine B.

关 键 词：石杉碱甲 石杉碱乙 乙酰胆碱酯酶 胆碱酯酶抑制剂 半数抑制浓度 半数致死量 

分 类 号：R285.5[医药卫生—中药学]