Tian Jing-Zhuo, Liu Su-Yan, Gao Yue, Zhang Bo-Li, Liang Ai-Hua
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China.
Institute of Radiation Medicine Sciences, Academy of Military Medical Sciences, Academy of Military Sciences Beijing 100850, China.
Zhongguo Zhong Yao Za Zhi. 2022 Jul;47(14):3693-3700. doi: 10.19540/j.cnki.cjcmm.20220520.401.
The safety problem of traditional Chinese medicine containing aristolochic acid is of great concern in China and abraod, which poses a challenge in clinical application and supervision. There are many types of aristolochic acid analogues(AAAs) and 178 have been reported. According to the structure, they are classified into aristolochic acids(AAs) and aristololactams(ALs). The toxi-city is remarkably different among AAAs of different types. For example, AA-Ⅰ has strong nephrotoxicity and carcinogenicity, and the toxicity of AA-Ⅱ is lower than that of AA-Ⅰ. Besides, AA-Ⅳa and AA-Ⅰa are considered to have no obvious nephrotoxicity and carcinogenicity. The types and content of AAAs are significantly different among traditional Chinese medicines derived from different Aristolochiaceae species. For example, Asari Radix et Rhizoma and Aristolochiae Herba mainly consist of AAAs without obvious toxicity(such as AA-Ⅳa). The content of AAAs in compound preparations is related to the proportions of the medicinals and the processing method. The content of AA-Ⅰ in some compound preparations is very low or below the detection limit. Therefore, the author concludes that AAAs of different types have different toxicity, but not all AAAs has nephrotoxicity and carcinogenicity. Moreover, the toxicity of traditional Chinese medicines containing AAAs should not be generalized and AA-Ⅰ and AA-Ⅱ should be emphasized. In this paper, it is suggested that traditional Chinese medicine containing AAAs should be used rationally and research, analysis, and toxicological study of AAAs species and content should be strengthened. In addition, limit standards of AA-Ⅰ and AA-Ⅱ should be formulated and science-based supervision should be performed.
含马兜铃酸的中药安全性问题在国内外备受关注,这给临床应用和监管带来了挑战。马兜铃酸类似物(AAAs)种类繁多,已报道的有178种。根据结构,它们被分为马兜铃酸(AAs)和马兜铃内酰胺(ALs)。不同类型的AAAs毒性差异显著。例如,AA-Ⅰ具有很强的肾毒性和致癌性,而AA-Ⅱ的毒性低于AA-Ⅰ。此外,AA-Ⅳa和AA-Ⅰa被认为没有明显的肾毒性和致癌性。不同马兜铃科植物来源的中药中AAAs的种类和含量差异显著。例如,细辛和马兜铃草药主要由无明显毒性的AAAs(如AA-Ⅳa)组成。复方制剂中AAAs的含量与药材比例和加工方法有关。一些复方制剂中AA-Ⅰ的含量很低或低于检测限。因此,作者得出结论,不同类型的AAAs毒性不同,但并非所有AAAs都具有肾毒性和致癌性。此外,含AAAs的中药毒性不应一概而论,应重点关注AA-Ⅰ和AA-Ⅱ。本文建议合理使用含AAAs的中药,加强对AAAs种类和含量的研究、分析及毒理学研究。此外,应制定AA-Ⅰ和AA-Ⅱ的限量标准并进行科学监管。