背景:Hedera螺旋L.(HH)叶和黄连(CR)传统上用于治疗呼吸系统疾病。AGNPP709,使用这两种草药的提取物配制而成,已被开发为祛痰和镇咳。
目的:目的是评估AGNPP709在实验大鼠体内的亚慢性毒性和毒代动力学特征。
方法:将AGNPP709以高达2.0g/kg/天的剂量口服给予大鼠,持续13周。在整个治疗期间测量各种健康参数。在治疗结束时,我们进行了尸检,并分析了其他参数.还对HederacosideC和小檗碱进行了毒物动力学分析,HH叶和CR的活性成分,分别,在用AGNPP709处理的大鼠的血浆中。
结果:AGNPP709治疗的大鼠表现出一些健康问题,例如减少饲料摄入量,差异白细胞(WBC)计数改变,女性血浆Alb/Glo比值增加,和减少男性的肾脏重量。然而,这些变化似乎是偶然的,属于该物种健康动物的典型范围。此外,HederacosideC和小檗碱的毒物动力学分析显示,在AGNPP709重复治疗期间,大鼠血浆中没有积累。
结论:我们的研究表明,在实验条件下,AGNPP709对大鼠没有任何有害作用。基于这些发现,在大鼠中,AGNPP709的未观察到的不良反应水平估计为2.0g/kg/天。
BACKGROUND: Hedera helix L. (HH) leaves and Coptidis rhizoma (CR) have traditionally been used to treat respiratory conditions. AG NPP709, which is formulated using extracts of both these herbs, has been developed as an expectorant and antitussive.
OBJECTIVE: The objective was to evaluate the subchronic toxicity and toxicokinetic characteristics of AG NPP709 in laboratory rats.
METHODS: AG NPP709 was orally administered to rats at doses of up to 2.0 g/kg/day for a duration of 13 weeks. Various health parameters were measured throughout the treatment period. At the end of the treatment, a necropsy was conducted and additional parameters were analyzed. Toxicokinetic analyses were also performed on hederacoside C and berberine, the active components of HH leaves and CR, respectively, in the plasma of rats treated with AG NPP709.
RESULTS: AG NPP709-treated rats exhibited several health issues, such as reduced feed intake, altered differential white blood cell (WBC) count, increased plasma Alb/Glo ratio in females, and reduced kidney weight in males. However, these changes appeared to be incidental and fell within the typical range for healthy animals of this species. Additionally, toxicokinetic analysis of hederacoside C and berberine showed no accumulation in the plasma of rats during the repeated treatments with AG NPP709.
CONCLUSIONS: Our study demonstrates that AG NPP709 does not have any harmful effects on rats under experimental conditions. Based upon these findings, the no observed adverse effect level of AG NPP709 can be estimated to be 2.0 g/kg/day in rats.