保元汤中具有心肌保护作用的活性成分及其潜在作用靶点研究

保元汤作为临床上广泛用于冠心病气虚血瘀兼阳虚证治疗的经典名方,其药效物质基础和作用机制迄今尚缺乏系统研究。为了阐明保元汤的活性物质基础及其作用机制,该文采用氧糖剥夺/复氧(OGD/R)诱导的H9c2心肌细胞损伤模型,对保元汤及其所含单体化合物进行心肌保护活性筛选;之后采用Pub Chem's Bio Assay database对具有活性的单体化合物进行生物靶标预测,并将预测的生物靶标进行归类整理,分析保元汤中活性成分与生物靶标之间的内在联系。结果发现保元汤水提物及其中17个单体化合物能够显著提高OGD/R诱导的H9c2心肌细胞存活率;虚拟靶标筛选研究结果显示,15个活性单体化合物与心肌保护相关的潜在作用机制主要涉及调控氧化应激通路、钙离子通路、线粒体保护、抗细胞凋亡等。该研究结果验证了保元汤具有心肌保护作用,并且阐明其保护作用是通过多成分、多靶点的网络调控作用实现的。该文研究结果为临床上保元汤用于冠心病的治疗提供了理论依据和参考。

Active compounds from Baoyuan decoction with myocardial protection activities and their potential targets

Baoyuan decoction (BYD) is a classical Chinese formula for coronary heart disease with Qi deficiency, blood stasis tonifying Qi and Yang deficiency. However, the chemical material basis and underlying action mechanisms of BYD still lack systemic stu-dy. In order to clarify the active compounds and the potential action mechanisms of BYD, the oxygen-glucose deprivation/recovery (OGD/R)-induced H9c2 cells injury models was used to screen the monomeric compounds of BYD with myocardial protection activity. PubChem''s BioAssay database was then used to analyze the potential targets of active monomeric compounds, classify the predicted biological targets, and analyze the internal relation between active compounds of BYD and biological targets. The screening results showed that BYD aqueous extract and 17 monomeric compounds could significantly increase the survival rate of OGD/R-induced H9c2 myocardial cells. The results of virtual targets screening study showed that 15 monomeric compounds and the potential mechanisms for myocardial protection were related to oxidative stress pathway, calcium ion pathway, mitochondrial protection, anti-apoptosis, etc. These results verified that BYD had myocardial protection effect, which was obtained by network regulation of multi-components and multi-targets. All these results provide the theoretical basis and references for the clinical usage of BYD in treatment of coronary heart disease.