Zan Ke, Wang Zhao, Hu Xiao-Wen, Li Yao-Lei, Wang Ying, Jin Hong-Yu, Zuo Tian-Tian, Ma Shuang-Cheng
National Institutes for Food and Drug Control, Beijing, China.
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
Front Pharmacol. 2023 Mar 23;14:1075010. doi: 10.3389/fphar.2023.1075010. eCollection 2023.
The aim of this study was to systematically explore the pyrrolizidine alkaloids (PAs) type, content and risk assessment in the three Boraginaceae used in TCM, involving Arnebia euchroma (AE), A. guttata (AG), and Lithospermum erythrorhizon (LE). A UHPLC-MS/MS method was established to simultaneously determine eight pyrrolizidine alkaloids (PAs), namely intermedine, lycopsamine, intermedine N-oxide, lycopsamine N-oxide, 7-acetyllycopsamine, 7-acetyllycopsamine N-oxide, echimidine N-oxide, and echimidine in the three herbs. Based on these results, the risk assessment was explored using the routine margin of exposure (MOE) combined with relative potency (REP) for oral and external usage, respectively. Imermedine and imermedine N-oxide were common components in the eight tested PAs. 7-acetyllycopsamine and its N-oxide were not detected in AE; echimidine and its N-oxide were not detected in AG; lycopsamine and its N-oxide, 7-acetyllycopsamine and its N-oxide were not detected in LE. The total contents of 8 PAs in 11 batches of AG was341.56-519.51 μg/g; the content in 15 batches of LE was 71.16-515.73 μg/g, and the content in 11 batches of AE was 23.35-207.13 μg/g. Based on these results, the risk assessment was explored using MOE combined with REP for oral and external usage, respectively. The findings of the risk assessment method of PAs based on MOE combined with the REP factor were consistent with the clinical toxicity results. As an oral herb, AE had low risk or no risk due to its low PA contents, and individual batches of LE were medium risk, while attention should be paid to their clinical use.AG was also low risk. The external use of the three Boraginaceae used in TCM was not associated with any risk. This study systematically explored the PA type and content of the three Boraginaceae used in TCM. Additionally, the refined risk assessment of PAs based on REP provided a more scientific basis for quality evaluation and rational use of the medicinal Boraginaceae used in TCM to improve public health.
本研究旨在系统探究三种用于中药的紫草科植物中吡咯里西啶生物碱（PAs）的类型、含量及风险评估，这三种植物分别为新疆紫草（AE）、黄花软紫草（AG）和紫草（LE）。建立了超高效液相色谱-串联质谱（UHPLC-MS/MS）法，用于同时测定这三种草药中的8种吡咯里西啶生物碱，即中蜂斗菜碱、石蒜碱、中蜂斗菜碱氮氧化物、石蒜碱氮氧化物、7-乙酰石蒜碱、7-乙酰石蒜碱氮氧化物、刺凌德草碱氮氧化物和刺凌德草碱。基于这些结果，分别采用常规暴露边际（MOE）结合相对效力（REP）对口服和外用进行风险评估。中蜂斗菜碱和中蜂斗菜碱氮氧化物是8种被测PAs中的常见成分。在新疆紫草中未检测到7-乙酰石蒜碱及其氮氧化物；在黄花软紫草中未检测到刺凌德草碱及其氮氧化物；在紫草中未检测到石蒜碱及其氮氧化物、7-乙酰石蒜碱及其氮氧化物。11批次黄花软紫草中8种PAs的总含量为341.56 - 519.51μg/g；15批次紫草中的含量为71.16 - 515.73μg/g，11批次新疆紫草中的含量为23.35 - 207.13μg/g。基于这些结果，分别采用MOE结合REP对口服和外用进行风险评估。基于MOE结合REP因子的PAs风险评估方法的结果与临床毒性结果一致。作为口服草药，新疆紫草因PAs含量低而风险低或无风险，个别批次的紫草有中度风险，临床使用时应予以关注。黄花软紫草风险也较低。三种用于中药的紫草科植物外用均无风险。本研究系统探究了三种用于中药的紫草科植物中PAs的类型和含量。此外，基于REP的PAs精细风险评估为中药中药用紫草科植物的质量评价和合理使用提供了更科学的依据，以改善公众健康。
