Mechanism Study On Enhancing Liver Detoxification Of YaJieShaBa

Objective:(1) The digitoxin is mainly metabolized in the liver, Observing digitoxin LD50in mice after oral administration of YaJieShaBa.(2) The pentobarbital sodium is mainly metabolized in the liver, observing the influence of YaJieShaBa on effect of pentobarbital sodium in sleep time of normal mice and CCI4model mice.(3) To investigate the effects of YaJieShaBa on the activities of drug-metabolism enzymes in liver microsome of normal rats and CCI4model rats.(4) To study the influence of YaJieShaBa on cytochrome P450isoforms CYP3A4、CYP1A2.Methods:(1) To observe change of digitoxin LD50and administration of YaJieShaBa. If YaJieShaBa is able to accelerate the liver metabolism of digitoxin, it can alleviate acute digitoxin toxicity.(2) To observe the influence of YaJieShaBa on effect of sleep latency and sleep time after the mice injected with pentobarbital sodium.(3)SD rats were given YaJieShaBa (2.43、0.27g/kg) via ig. gtt once a day for14days. The contents of cytochrome P450, cytochrome b5in rat liver microsome and the activity of ERD, ADM were assayed respectively.(4) A "Cocktail" approach in rat by HPLC was established and validated to evaluate the inductive effect on cytochrome P450isoforms CYP3A4、CYP1A2.Results:(1) The digitoxin LD50increased in mice after the YaJieShaBa was administered, suggesting that YaJieShaBa(3.51g/kg) can detoxify.(2) After intraperitoneal injection of pentobarbital sodium, the high-dose group of YaJieShaBa (3.51g/kg) could prolong sleep latency in normal mice (P<0.01), and shorten sleep time of normal mice and CCI4model mice (P<0.05); the low-dose group had no statistically significant.(3) For normal rats, YaJieShaBa (2.43g/kg) could improve the content of CYP450and Cyt b5, induced the activity of ERD and ADM (P<0.01, P<0.05); For liver injury induced by CCl4in rats, YaJieShaBa (2.43g/kg) could improve the content of C YP450and Cyt b5(P<0.05), had no effect on the activity of ERD and ADM.(4) The result suggested that YaJieShaBa could induce CYP3A4、CYP1A2(P<0.05)Conclusions:(1)The high-dose group of YaJieShaBa (3.51g/kg) could increase digitoxin LD50in mice, prolong sleep latency in normal mice, and shorten sleep time of normal mice and CCI4model mice. It could accelerate the metabolism of pentobarbital sodium, induct hepatic drug metabolizing enzyme in mice.(2) High-dose of YaJieShaBa(2.43g/kg) could improve the content of CYP450and Cyt b5for normal rats and CCI4model rats, induce the activity of ERD and ADM, and increases protein expression of CYP3A and CYP2E1., YaJieShaBa could induce cytochrome P450isoforms CYP3A4、CYP1A2.