Guo Xiaozhen, Xie Yang, Lian Shan, Li Zhixiong, Gao Yu, Xu Zhou, Hu Pei, Chen Mingcang, Sun Zhaolin, Tian Xiaoting, Huang Chenggang
Shanghai Institute of Material Medica, Chinese Academy of Science, Shanghai, China.
University of Chinese Academy of Science, Beijing, China.
Biomed Chromatogr. 2018 Mar;32(3). doi: 10.1002/bmc.4124. Epub 2017 Nov 22.
Pulsatilla chinensis saponins, the major active components in the herb, have drawn great attention as potential hepatitis B virus infection and hepatoma treatments. Here, a sensitive and accurate HPLC-MS/MS method was established for simultaneous determination of three saponins - anemoside B4, anemoside A3 and 23-hydroxybetulinic acid - in rat plasma and liver, and fully validated. The method was successfully applied to a pharmacokinetics and liver distribution study of P. chinensis saponins. Consequently, 23-hydroxybetulinic acid, with an extremely low content in the P. chinensis saponins, exhibited the highest exposure in the liver and in sites before and after hepatic disposition, namely, in the portal vein plasma and systemic plasma, followed by anemoside B4, which showed the highest content in the herb, whereas anemoside A3 displayed quite limited exposure. The hepatic first-pass effects were 71% for 23-hydroxybetulinic acid, 27% for anemoside B4 and 37% for anemoside A3, corresponding to their different extents of liver distribution. To our knowledge, this is the first investigation on the liver first-pass effect and distribution of P. chinensis saponins to date. These results also provide valuable information for the understanding of the pharmacological effect of P. chinensis saponins on liver diseases.
白头翁皂苷是该草药中的主要活性成分，作为潜在的乙型肝炎病毒感染和肝癌治疗药物受到了广泛关注。在此，建立了一种灵敏、准确的HPLC-MS/MS方法，用于同时测定大鼠血浆和肝脏中的三种皂苷——白头翁皂苷B4、白头翁皂苷A3和23-羟基白桦酸，并进行了全面验证。该方法成功应用于白头翁皂苷的药代动力学和肝脏分布研究。结果表明，在白头翁皂苷中含量极低的23-羟基白桦酸在肝脏以及肝处置前后的部位，即门静脉血浆和全身血浆中表现出最高的暴露量，其次是白头翁皂苷B4，其在草药中的含量最高，而白头翁皂苷A3的暴露量相当有限。23-羟基白桦酸的肝首过效应为71%，白头翁皂苷B4为27%，白头翁皂苷A3为37%，这与它们不同程度的肝脏分布相对应。据我们所知，这是迄今为止对白头翁皂苷肝首过效应和分布的首次研究。这些结果也为理解白头翁皂苷对肝脏疾病的药理作用提供了有价值的信息。
