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

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(-6)g·L^(-1)、8.40×10(-1)、8.40×10^(-6)g·L(-6)g·L^(-1)、9.74×10(-1)、9.74×10^(-6)g·L(-6)g·L^(-1)和13.12×10(-1)和13.12×10^(-6)g·L(-6)g·L^(-1),其中Hup A用量分别为5.36×10(-1),其中Hup A用量分别为5.36×10^(-6)g·L(-6)g·L^(-1)、4.20×10(-1)、4.20×10^(-6)g·L(-6)g·L^(-1)、3.25×10(-1)、3.25×10^(-6)g·L(-6)g·L^(-1)和2.62×10(-1)和2.62×10^(-6)g·L(-6)g·L^(-1),而对照品Hup A和Hup B的IC_(50)分别为4.82×10(-1),而对照品Hup A和Hup B的IC_(50)分别为4.82×10^(-6)g·L(-6)g·L^(-1)和854.65×10(-1)和854.65×10^(-6)g·L(-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);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)、(13.76±2.98)mg·kg^(-1)、(20.33±4.29)mg·kg(-1)、(20.33±4.29)mg·kg^(-1)和>40.00 mg·kg(-1)和>40.00 mg·kg^(-1),其中Hup A用量分别为6.09 mg·kg(-1),其中Hup A用量分别为6.09 mg·kg^(-1)、6.74 mg·kg(-1)、6.74 mg·kg^(-1)、6.57 mg·kg(-1)、6.57 mg·kg^(-1)和8.00 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),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)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。

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

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 acetylcholinesterase 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 IC_(50) values were 8.04×10~(-6),8.40×10~(-6),9.74×10~(-6) and 13.12×10~(-6) g·L~(-1) respectively,and among them the dosages of Hup A were 5.36×10~(-6),4.20×10~(-6),3.25×10~(-6) and 2.62×10~(-6) g·L~(-1)respectively.The IC_(50) values of the control Hup A and Hup B were 4.82×10~(-6),854.65×10~(-6) g·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.