Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, PR China.
Phytomedicine. 2013 Dec 15;21(1):82-9. doi: 10.1016/j.phymed.2013.06.012. Epub 2013 Aug 27.
Daphnane-type diterpenoids (DDs) are the main types of plant diterpene orthoesters known and have remarkable biological activities. However, the in vivo toxicity and pharmacokinetic profile of DDs remains unkonwn. The aim of this study was to investigate the toxicity and pharmacokinetic profile of DDs from Genkwa Flos (Thymelaeaceae). The toxicity of diterpenoids was evaluated after oral administration of total diterpenoids extract from Genkwa Flos to rats, and the blood concentration of diterpenoids was analyzed by ultra performance liquid chromatography tandem triple-quadrupole mass spectrometry (UPLC-TQ-MS). The diterpenoids were confirmed to be the toxic components of Genkwa Flos. The pharmacokinetic profile of these diterpenoids was quite different due to their different structures. Although the contents of yuanhuafine and yuanhuapine were low in the extract, the blood concentrations were extremely high. In contrary, the contents of genkwanine F and Wikstroemia factor M1 in the extract were much higher, but they could not be detected in the blood. This result implied that yuanhuafine and yuanhuapine but not genkwanine F and Wikstroemia factor M1 were the potentail toxic components of Genkwa Flos in vivo. This paper shows for the first time the toxicity of diterpenoids from Genkwa Flos was correlated with their blood concentration and when DDs were used for medicinal purposes, their contents in herb as well as their blood concentrations should be considered.
瑞香烷型二萜类化合物（DDs）是已知植物二萜异戊酸酯的主要类型，具有显著的生物活性。然而，DDs 的体内毒性和药代动力学特征尚不清楚。本研究旨在探讨芫花中的 DDs 的毒性和药代动力学特征。采用大鼠口服芫花总二萜提取物的方法评价二萜的毒性，并用超高效液相色谱串联三重四极杆质谱（UPLC-TQ-MS）分析二萜的血药浓度。结果表明，二萜类化合物是芫花的毒性成分。由于结构不同，这些二萜类化合物的药代动力学特征有很大差异。虽然提取物中芫花定和芫花瑞林的含量较低，但血药浓度极高。相反，提取物中芫花乙素 F 和广防己甲素 M1 的含量要高得多，但在血液中却无法检测到。这一结果表明，芫花中的芫花定和芫花瑞林而不是芫花乙素 F 和广防己甲素 M1 是芫花在体内的潜在毒性成分。本文首次表明芫花中二萜类化合物的毒性与其血药浓度有关，当 DDs 用于药用目的时，应考虑草药中的含量及其血药浓度。
