Department of Pharmacy, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai 200003, China.
Research and Development Center of Chinese Medicine Resources and Biotechnology, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Biomed Pharmacother. 2021 Dec;144:112354. doi: 10.1016/j.biopha.2021.112354. Epub 2021 Oct 28.
Shengxian Decotion (SXT), a well-known Traditional Chinese Medicine (TCM) formula composed of Astragali Radix, Bupleuri Radix, Cimicifugae Rhizoma, Anemarrhenae Rhizoma and Platycodonis Radix, is clinically considered as an effective formula against cardiovascular diseases. However, the exact effective substance of SXT in treating chronic heart failure (CHF) still remains unclear. In the current study, we investigated the benefit of SXT in doxorubicin (DOX)-induced CHF rats and established a UHPLC-MS/MS method to simultaneously determine 18 key compounds in a subsequent comparative pharmacokinetic study in normal and CHF rats. Histopathological studies, transmission electron microscopy, and echocardiography were applied to assess the therapeutic effect of SXT on DOX-induced CHF rats, which indicated that SXT significantly ameliorated DOX-induced CHF, similar to enalapril. In addition, we successfully established a UHPLC-MS/MS method to determine the pharmacokinetics of the components in rat plasma, which was validated with good linearity, inter-day and intra-day precisions and accuracies, matrix effects, extraction recovery, and stability values. Our results showed that only astragaloside IV showed increased plasma exposure in the CHF rats, while saikosaponin A, quercetin, timosaponin B-II, ferulic acid, isoferulic acid and formononetin decreased compared to their pharmacokinetic characteristics in the normal and CHF rats. This study demonstrates that SXT enjoys obvious therapeutic effect on DOX-induced CHF rats, and the altered metabolism of some compounds in SXT is affected by the pathological state of CHF rats. Our findings provide a better understanding of the in vivo exposure to complex compounds of SXT, supporting effective substance screening and further investigation of the therapeutic mechanism.
生脉饮（SXT）是一种著名的中药方剂，由黄芪、柴胡、桂枝、知母和桔梗组成，临床上被认为是治疗心血管疾病的有效方剂。然而，SXT 治疗慢性心力衰竭（CHF）的确切有效物质仍不清楚。在本研究中，我们研究了 SXT 在阿霉素（DOX）诱导的 CHF 大鼠中的益处，并建立了 UHPLC-MS/MS 方法，以在随后的正常和 CHF 大鼠比较药代动力学研究中同时测定 18 种关键化合物。组织病理学研究、透射电子显微镜和超声心动图用于评估 SXT 对 DOX 诱导的 CHF 大鼠的治疗效果，结果表明 SXT 显著改善了 DOX 诱导的 CHF，与依那普利相似。此外，我们成功建立了一种 UHPLC-MS/MS 方法来测定大鼠血浆中成分的药代动力学，该方法具有良好的线性、日内和日间精密度和准确度、基质效应、提取回收率和稳定性值。我们的结果表明，只有黄芪甲苷 IV 显示在 CHF 大鼠中血浆暴露增加，而柴胡皂苷 A、槲皮素、知母皂苷 B-II、阿魏酸、异阿魏酸和芒柄花素的药代动力学特征与正常和 CHF 大鼠相比有所降低。这项研究表明，SXT 对 DOX 诱导的 CHF 大鼠具有明显的治疗作用，SXT 中一些化合物的代谢变化受 CHF 大鼠病理状态的影响。我们的发现提供了对 SXT 中复杂化合物体内暴露的更好理解，支持有效物质筛选和进一步研究治疗机制。
