A Strategy for Optimizing the Combination of Active Components Based on Chinese Medicinal Formula Sheng-Mai-San for Myocardial Ischemia
A Strategy for Optimizing the Combination of Active Components Based on Chinese Medicinal Formula Sheng-Mai-San for Myocardial Ischemia
复制标题
中药生脉散治疗心肌缺血活性成分优化组合策略
DOI：
10.1159/000487572
复制
发表时间：
2018-01-01
影响因子：
--
通讯作者：
Yu, Bo-Yang
中科院分区：
文献类型：
--
作者：
Li, Fang;Fan, Xiao-Xue;Yu, Bo-Yang
背景/目的：中医已在临床实践中使用了数千年，在针对复杂疾病的体内疗效方面积累了相当多的知识。中药方剂是由数百种具有多种潜在靶点的化学成分混合而成，本质上是一种多成分药物的联合治疗。然而，由于物质的不明确和分子机制的不明确，阻碍了其进一步发展和国际化。因此，有必要在中药有效成分与临床疗效相结合的基础上开发新的现代药物。本研究旨在以生脉散为基础，寻找治疗心肌缺血有效成分的最佳组合比例。方法：在对生脉散治疗心肌缺血的初步研究和参考相关文献的基础上，选择人参皂苷Rbl (G)、ruscogenin (R)和五味子苷(S) 3种具有代表性的成分进行优化设计研究。首先，采用正交设计法，探讨异丙肾上腺素和垂体后叶素对不同小鼠心肌缺血的适宜配伍比例。然后，通过多模型、多指标的均匀设计，对不同比例组合进行进一步优化。最后，在缺血/再灌注损伤心肌模型、慢性间歇性缺氧模型和急性梗死模型中验证联合用药的保护作用。结果：经实验筛选得到的优化组合GRS （G: 6 mg/kg, R: 0.75 mg/kg, S: 6 mg/kg）对心肌缺血损伤具有显著的保护作用，表现为心肌梗死面积减小，组织学特征改善，心肌髓过氧化物酶（MPO）、丙二醛（MDA）、钙超载降低，血清乳酸脱氢酶（LDH）、肌酸激酶MB同功酶（CK-MB）、心肌肌钙蛋白I （cTn-I）活性降低。此外，还研究了组合GRS中三个组分的相互作用。与G、R、S相比，联合用药可显著降低血清CK-MB、ctn - 1浓度，减小心肌梗死面积，显示了联合用药治疗心肌缺血的优势。结论：优化后的复方GRS对心肌缺血损伤具有明显的保护作用，且效果与生脉制剂相似，为进一步在中药方剂基础上开发具有肯定疗效的心血管疾病现代新药提供了一定的药理学依据。(C) 2018年，作者：s . Karger AG，巴塞尔出版。
Background/Aims: Traditional Chinese medicine (TCM) has been used in clinical practice for thousands of years and has accumulated considerable knowledge concerning the in vivo efficacy of targeting complicated diseases. TCM formulae are a mixture of hundreds of chemical components with multiple potential targets, essentially acting as a combination therapy of multi-component drugs. However, the obscure substances and the unclear molecular mechanisms are obstacles to their further development and internationalization. Therefore, it is necessary to develop new modern drugs based on the combination of effective components in TCM with exact clinical efficacy. In present study, we aimed to detect optimal ratio of the combination of effective components based on Sheng-Mai-San for myocardial ischemia. Methods: On the basis of preliminary studies and references of relevant literature about Sheng-Mai-San for myocardial ischemia, we chose three representative components (ginsenoside Rbl (G), ruscogenin (R) and schisandrin (S)) for the optimization design studies. First, the proper proportion of the combination was explored in different myocardial ischemia mice induced by isoproterenol and pituitrin based on orthogonal design. Then, the different proportion combinations were further optimized through uniform design in a multi-model and multi-index mode. Finally, the protective effect of combination was verified in three models of myocardial ischemia injured by ischemia/reperfusion, chronic intermittent hypoxia and acute infarction. Results: The optimized combination GRS (G: 6 mg/kg, R: 0.75 mg/kg, S: 6 mg/kg) obtained by experimental screening exhibited a significant protective effect on myocardial ischemia injury, as evidenced by decreased myocardium infarct size, ameliorated histological features, decreased myocardial myeloperoxidase (MPO) and malondiadehyde (MDA), calcium overload, and decreased serum lactate dehydrogenase (LDH), creatine kinase MB isoenzyme (CK-MB), cardiac troponin I (cTn-I) activity. In addition, the interactions of three components in combination GRS were also investigated. The combination, compared to G, R and S, could significantly reduce the concentration of serum CK-MB and cTn-I, and decrease myocardial infarct size, which demonstrated the advantages of this combination for myocardial ischemia. Conclusion: Our results demonstrated that the optimized combination GRS could exert significant cardioprotection against myocardial ischemia injury with similar effect compared to Sheng Mai preparations, which might provide some pharmacological evidences for further development of new modern Chinese drug for cardiovascular diseases basing on traditional Chinese formula with affirmative therapeutic effect. (C) 2018 The Au thor(s) Published by S. Karger AG, Basel.