The Ministry of Education Key Laboratory for Standardization of Chinese Medicines and the State Administration of Traditional Chinese Medicine Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
The Third Hospital of Changzhou, Changzhou, Jiangsu Province 213001, China.
Phytomedicine. 2019 Feb 15;54:77-88. doi: 10.1016/j.phymed.2018.06.015. Epub 2018 Jul 2.
The roots of Gynura japonica are used as traditional medicine for treating blood stasis or traumatic injury even though hundreds of hepatic sinusoidal obstruction syndrome cases have been reported after consumption of the roots, which contain large amounts of hepatotoxic pyrrolizidine alkaloids (HPAs). However, no information is available about the toxic compounds in the aerial parts of G. japonica, which are also used as herbal medicines and even vegetables in several areas. Thus, the toxic chemicals in the aerial parts of G. japonica, i.e., HPAs, must be urgently identified.
In this study, we aimed to 1) identify the toxic compounds in different medicinal parts and 2) examine the hepatotoxicity of G. japonica.
A total of 35 batches of the roots and aerial parts of G. japonica were collected from different sources and analyzed for HPAs. The hepatotoxicity of different extracts (i.e., total extracts [TE] and total alkaloids [TA]) and a single compound (i.e., senecionine) was evaluated on mice.
Qualitative analysis of HPAs was performed using an ultra-performance liquid chromatography (UPLC)-mass spectrometry (MS)-parent ion scan approach, whereas a quantitative assay was performed by a UPLC-MS-selected ion monitoring approach. Male C57BL mice were orally administered the different extracts or the single compound at dosages equivalent to 50 mg HPAs/kg body weight. The sera and the livers were collected at 48 h after treatment and used to evaluate the hepatotoxicity through serum clinical biomarkers assay, liver histology, and bile acid profiling.
A total of 21 HPAs were identified in the roots and the aerial parts. The roots contained higher levels of HPAs (4.90 mg/g) than did the aerial parts (2.21 mg/g). TE and TA induced similar acute liver injuries, but senecionine was considerably more toxic than these extracts. Mice treated with TE showed significantly impaired bile acid homeostasis in the sera and the livers.
The roots and aerial parts of G. japonica contained large amounts of HPAs, including senecionine, which were responsible for the hepatotoxicity of G. japonica. Bile acid homeostasis was uniquely impaired after exposure to the plant. Therefore, neither the roots nor the aerial parts of G. japonica should be consumed as medicines or vegetables.
尽管已有数百例因食用含有大量肝毒性吡咯里西啶生物碱（HPAs）的其根部而导致的肝窦阻塞综合征病例报告，但该植物的根部仍被用作传统药物来治疗血瘀或外伤性损伤。然而，目前尚无关于其地上部分的有毒化合物的信息，这些地上部分也被用作草药，甚至在某些地区也被用作蔬菜。因此，急需确定其地上部分中的有毒化合物，即 HPAs。
本研究旨在 1）鉴定不同药用部位的有毒化合物，2）研究其地上部分的肝毒性。
共采集了 35 批不同来源的该植物的根和地上部分，并用超高效液相色谱（UPLC）-质谱（MS）-母离子扫描法分析 HPAs。用不同提取物（总提取物[TE]和总生物碱[TA]）和单一化合物（即千里光碱）对小鼠进行了肝毒性评估。
采用 UPLC-MS-母离子扫描法对 HPAs 进行定性分析，采用 UPLC-MS-选择离子监测法进行定量分析。雄性 C57BL 小鼠经口给予不同提取物或单一化合物，剂量相当于 50mg HPAs/kg 体重。治疗后 48h 采集血清和肝脏，通过血清临床生物标志物检测、肝脏组织学和胆汁酸谱分析评估肝毒性。
在根和地上部分中共鉴定出 21 种 HPAs。根中 HPAs 的含量（4.90mg/g）高于地上部分（2.21mg/g）。TE 和 TA 诱导了相似的急性肝损伤，但千里光碱比这些提取物的毒性大得多。用 TE 处理的小鼠在血清和肝脏中表现出明显的胆汁酸代谢紊乱。
该植物的根和地上部分含有大量的 HPAs，包括千里光碱，这些物质是其肝毒性的原因。暴露于该植物后，胆汁酸的动态平衡受到了独特的损害。因此，无论是根还是地上部分都不应该作为药物或蔬菜食用。
