Chen Jinfeng, Guo Xiaoyu, Lu Yingyuan, Shi Mengling, Mu Haidong, Qian Yi, Wang Jinlong, Lu Mengqiu, Zhao Mingbo, Tu Pengfei, Song Yuelin, Jiang Yong
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
Pharmaceutics. 2020 Feb 20;12(2):180. doi: 10.3390/pharmaceutics12020180.
The combination of extract (CTE) and notoginseng total saponins (NGTS), namely, CNP, presents a synergistic effect on myocardial ischemia protection. Herein, comparative pharmacokinetic studies between CNP and CTE/NGTS were conducted to clarify their synergistic mechanisms. A large volume direct injection ultra-high performance liquid chromatography-tandem mass spectrometry (LVDI-UHPLC-MS/MS) platform was developed for sensitively assaying the multi-component pharmacokinetic and in vitro cocktail assay of cytochrome p450 (CYP450) before and after compatibility of CTE and NGTS. The pharmacokinetic profiles of six predominantly efficacious components of CNP, including hydroxysafflor yellow A (HSYA); ginsenosides Rg (GRg), Re (GRe), Rb (GRb), and Rd (GRd); and notoginsenoside R (NGR), were obtained, and the results disclosed that CNP could increase the exposure levels of HSYA, GRg, GRe, GRb, and NGR at varying degrees. The in vitro cocktail assay demonstrated that CNP exhibited more potent inhibition on CYP1A2 than CTE and NGTS, and GRg, GRb, GRd, quercetin, kaempferol, and 6-hydroxykaempferol were found to be the major inhibitory compounds. The developed pharmacokinetic interaction-based strategy provides a viable orientation for the compatibility investigation of herb medicines.
提取物（CTE）与人参总皂苷（NGTS）的组合，即CNP，对心肌缺血保护具有协同作用。在此，进行了CNP与CTE/NGTS之间的比较药代动力学研究，以阐明其协同机制。开发了一种大容量直接进样超高效液相色谱-串联质谱（LVDI-UHPLC-MS/MS）平台，用于灵敏地测定CTE与NGTS配伍前后的多组分药代动力学以及细胞色素P450（CYP450）的体外鸡尾酒试验。获得了CNP六种主要有效成分的药代动力学特征，包括羟基红花黄色素A（HSYA）、人参皂苷Rg（GRg）、Re（GRe）、Rb（GRb）和Rd（GRd）以及三七皂苷R1（NGR），结果表明CNP可不同程度地提高HSYA、GRg、GRe、GRb和NGR的暴露水平。体外鸡尾酒试验表明，CNP对CYP1A2的抑制作用比CTE和NGTS更强，并且发现GRg、GRb、GRd、槲皮素、山奈酚和6-羟基山奈酚是主要的抑制化合物。所开发的基于药代动力学相互作用的策略为草药配伍研究提供了一个可行的方向。
