Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, China.
Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, China.
J Ethnopharmacol. 2023 Oct 28;315:116568. doi: 10.1016/j.jep.2023.116568. Epub 2023 May 20.
The nephrotoxicity and carcinogenicity induced by traditional Chinese medicines (TCMs) containing aristolochic acids (AAs) and related compound preparations have greatly limited their clinical application. While the toxicity of AA-I and AA-II is relatively clear, there are marked differences in the toxic effects of different types of aristolochic acid analogues (AAAs). Thus, the toxicity of TCMs containing AAAs cannot be evaluated based on the toxicity of a single compound.
To systematically investigate the toxicity induced by Zhushalian (ZSL), Madouling (MDL) and Tianxianteng (TXT) as representative TCMs derived from Aristolochia.
AAA contents in ZSL, MDL and TXT were determined using HPLC. Subsequently, mice were treated for 2 weeks with high (H) and low (L) dosages of TCMs containing total AAA contents of 3 mg/kg and 1.5 mg/kg, respectively. Toxicity was evaluated using biochemical and pathological examination and was based on organ indices. Correlations between AAA contents and induced toxicity were analysed using multiple methods.
Of the total AAA content, ZSL contained mainly AA-I and AA-II (>90%, of which AA-I accounted for 49.55%). AA-I accounted for 35.45% in MDL. TXT mainly contained AA-IVa (76.84%) and other AAAs accounted for <10%. Short-term toxicity tests indicated that ZSL and high-dose MDL induced obvious renal interstitial fibrosis and gastric injury, whereas TXT (high and low dosages) caused only slight toxicity. Correlation analysis suggested that AA-I might be the critical hazard factor for toxicity.
The toxicity of TCMs containing AAAs cannot be generalised. The toxicity of TXT is relatively low compared with those of ZSL and MDL. The toxicity of Aristolochia depends mainly on the AA-I content; therefore, control of AA-I levels in TCMs and related compound preparations is required to reduce the risk of toxicity associated with the use of Aristolochia herbs in clinical settings.
含马兜铃酸（AAs）的中药（TCMs）和相关化合物制剂引起的肾毒性和致癌性极大地限制了它们的临床应用。虽然 AA-I 和 AA-II 的毒性相对明确，但不同类型的马兜铃酸类似物（AAAs）的毒性作用有明显差异。因此，不能根据单一化合物的毒性来评估含 AAAs 的 TCMs 的毒性。
系统研究以朱砂莲（ZSL）、马兜铃（MDL）和天仙藤（TXT）为代表的源自马兜铃的 TCMs 引起的毒性。
采用 HPLC 法测定 ZSL、MDL 和 TXT 中的 AAA 含量。随后，用含总 AAA 含量分别为 3mg/kg 和 1.5mg/kg 的高（H）、低（L）剂量 TCM 处理小鼠 2 周。根据生化和病理检查评估毒性，并基于器官指数进行评估。采用多种方法分析 AAA 含量与诱导毒性之间的相关性。
在总 AAA 含量中，ZSL 主要含有 AA-I 和 AA-II（>90%，其中 AA-I 占 49.55%）。MDL 中 AA-I 占 35.45%。TXT 主要含有 AA-IVa（76.84%），其他 AAAs 含量<10%。短期毒性试验表明，ZSL 和高剂量 MDL 引起明显的肾间质纤维化和胃损伤，而 TXT（高、低剂量）仅引起轻微毒性。相关分析表明，AA-I 可能是毒性的关键危害因素。
不能一概而论地认为含 AAAs 的 TCMs 具有毒性。与 ZSL 和 MDL 相比，TXT 的毒性相对较低。马兜铃的毒性主要取决于 AA-I 含量；因此，需要控制 TCMs 和相关化合物制剂中的 AA-I 水平，以降低在临床环境中使用马兜铃属草药相关毒性的风险。
