The aim of this study was to investigate the synergistic effect and underlying mechanism of compatibility of Aconiti Lateralis Radix Praeparata water-soluble alkaloids (FWA) and Ginseng Radix et Rhizoma total ginsenosides (RTG) on propafenone hydrochloride induced acute heart failure (AHF) rats. Firstly, hemodynamics and serum biochemical indexes were measured to observe the therapeutic effect of FWA, RTG and their compatibility on AHF rats. Non-target serum metabolomics and multicomponent pharmacokinetic experiments were then performed to reveal the mechanism from the two aspects of body reaction and drug behavior in vivo. Data showed the haemodynamics indexes (maximum change rate of left ventricular pressure, heart rate) and neuroendocrine cytokines (TNF-α and Nt-proBNP) levels in rats treated by compatibility of FWA and RTG were improved more significantly than that treated by single drug. Through metabolomics analysis, six metabolites, including L-pipecolic acid, L-arginine, uric acid, N-benzoylglycine, sphingosine-1-phosphate and phosphatidylinositol lyso 16:0, were selected and identified as the potential biomarkers of the synergistic effect. Furthermore, lysine degradation, arginine and proline metabolism, purine metabolism, sphingolipid metabolism, etc. were the differential pathways involved. The results of pharmacokinetics showed C_max, AUC_last and t_1/2 of the four components (uracil, salsolinol, guanosine, higenamine) of FWA in compatibility group were obviously higher than that in single drug group, which indicated the absorption and bioavailability of these alkaloids were increased, and the residence time was prolonged after FWA combined with RTG. In conclusion, the therapeutic effect of FWA-RTG on AHF rats was enhanced and that might because the compatibility of FWA-RTG affected the process of some metabolites in AHF rats, and pharmacokinetic behavior of components in FWA was obviously influenced after co-administered with RTG.

这项研究的目的是调查乌头水溶性人生物碱（FWA）和人参总人参总皂苷（RTG）对盐酸普罗帕酮诱发的急性心力衰竭（AHF）大鼠的协同作用和相容性的潜在机制。首先，测量血流动力学和血清生化指标，观察FWA，RTG及其对AHF大鼠的治疗作用。然后进行了非目标血清代谢组学和多组分药代动力学实验，从体内反应和体内药物行为两个方面揭示了机理。数据显示，与单药治疗相比，FWA和RTG相容性治疗的大鼠的血流动力学指数（最大心室压力变化率，心律）和神经内分泌细胞因子（TNF-α和Nt-proBNP）水平显着提高。通过代谢组学分析，选择了六种代谢物，包括L-哌酸，L-精氨酸，尿酸，N-苯甲酰甘氨酸，鞘氨醇-1-磷酸和磷脂酰肌醇溶血素16：0，并将其识别为协同作用的潜在生物标志物。此外，赖氨酸降解，精氨酸和脯氨酸代谢，嘌呤代谢，鞘脂代谢等是涉及的差异途径。药代动力学结果显示C _max，AUC _last和t _1/2相容性组中FWA的4种成分（尿嘧啶，Salsolinol，鸟苷，组胺）明显高于单药组，这表明这些生物碱与FWA结合后吸收和生物利用度增加，并且停留时间延长。 RTG。总之，FWA-RTG对AHF大鼠的治疗作用增强了，这可能是因为FWA-RTG的相容性影响了AHF大鼠某些代谢产物的过程，与FWA-RTG并用后其药代动力学行为受到明显影响。 RTG。