Gynura japonica (also named Tusanqi in Chinese) is used as a folk herbal medicine for treating blood stasis or traumatic injury. However, hundreds of hepatic sinusoidal obstruction syndrome (HSOS) cases have been reported after consumption of preparations made from G. japonica because it contains large amounts of hepatotoxic pyrrolizidine alkaloids (PAs). To date, blood pyrrole-protein adducts (PPAs) are suggested as biomarkers for the diagnosis of PA-induced HSOS in clinics. However, the concentration of PPAs in the blood is greatly affected by several factors including the amount of PA exposure, herb intake period, and blood sampling time after the last exposure. In present study, the kinetic characters of PPAs in serum and liver as well as other potential target organs were studied systematically and comprehensively following multiple exposures of PAs in G. japonica extract (GJE). As results, PPAs content reached to a plateau both in serum and liver after the mice were treated with GJE for 2 weeks on daily basis. PPAs cleared significantly slower in liver (T1/2ke∼184.6 h, ∼7.7 days) than in serum (T1/2ke∼95.8 h, ∼4.0 days). Although more than 90 % PPAs were removed 2 weeks after the last dosing, PPAs still persisted in the liver until the end of the experiment, i.e. 8 weeks after the last dosing. The results would be of great help for understanding the importance of PPAs for PA-induced toxicity and its detoxification.

译文

绞股蓝(Gynura japonica)(民间也称为土三七)被用作治疗血瘀或外伤的民间草药。但是,据报道,食用由粳稻制成的制剂后,有数百例肝窦正弦阻塞综合征(HSOS)病例,因为其中含有大量的肝毒性吡咯烷核生物碱(PAs)。迄今为止,在临床上建议将血液吡咯蛋白加合物(PPA)作为诊断PA诱导的HSOS的生物标记。但是,血液中PPA的浓度受几个因素的很大影响,包括PA暴露量,草药摄入时间和最后一次暴露后的采血时间。在本研究中,系统地和全面地研究了粳稻提取物(GJE)中PA的多次暴露后,血清,肝脏和其他潜在靶器官中PPA的动力学特征。结果,每天用GJE治疗小鼠2周后,血清和肝脏中的PPA含量均达到平台。肝脏(T1 / 2ke〜184.6h,〜7.7天)中的PPA清除速度明显慢于血清(T1 / 2ke〜95.8h,〜4.0天)中的清除速度。尽管在最后一次给药后2周内去除了90%以上的PPA,但直到实验结束时(即最后一次给药后8周),PPA仍在肝脏中持续存在。该结果对于理解PPA对PA诱导的毒性及其解毒的重要性将有很大的帮助。

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