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Abstract：
As a well-known classical Chinese medicine prescription, Shengxian Decoction (SXD) has been applied for a century to treat cardiovascular diseases, especially coronary heart disease (CHD), but the potentially effective compounds and underlying mechanisms remain unclear. With ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF/MS) and network pharmacology analysis, the potential effective compounds of SXD and their pharmacological mechanisms against CHD were identified and revealed. 57 effective compounds with favorable pharmacokinetic characteristics and biological activities were screened through UPLC-Q-TOF/MS analysis, database and literature mining, interacting with 96 CHD-related targets to support potential synergistic therapeutic actions. Systematic analysis of the PPI network and microarray data further revealed six core targets, including TNF, IL-1β, IL-6, TP53, VEGFA and PTGS2, which were mainly involved in fluid shear stress and atherosclerosis, lipid and atherosclerosis, PI3K-Akt signaling pathway et al. Moreover, the proposed contribution indexes of effective compounds indicated these compounds, including isoferulic acid, quercetin, calycosin, ferulic acid, kaempferol, calycosin 7-O-glycoside, formononetin, astragaloside IV and saikosaponin D, as the core compounds of SXD. The molecular docking results confirmed that those core compound-target pairs exhibited strong binding energy. Furthermore, we validated that SXD significantly alleviated myocardial tissue injury in CHD rats and reversed H/R-induced decreases in H9c2 cell viability by attenuating the production of TNF, IL-6 and IL-1β, and reducing cardiomyocyte apoptosis via down-regulating the TP53, caspase3 and cytochrome C mRNA expression levels as well as caspase3, caspase9 and cytochrome C protein expression levels according to RT-qPCR and Western blot results. Our findings explained the pharmacological mechanisms underlying the effectiveness of SXD in the treatment of CHD, and laid a foundation for future basic and clinical research of SXD.
摘要：
作为著名的中医方剂,圣仙汤（SXD）已应用于心血管疾病治疗已有一个世纪，尤其是冠心病，但潜在有效的化合物和潜在机制仍不清楚.采用超高效液相色谱-四极杆-飞行时间质谱(UPLC-Q-TOF/MS)和网络药理学分析,本研究鉴定并揭示了SXD的潜在有效化合物及其抗CHD的药理机制。通过UPLC-Q-TOF/MS分析筛选出57个具有良好药代动力学特征和生物学活性的有效化合物,数据库和文献挖掘，与96个CHD相关靶标相互作用，以支持潜在的协同治疗作用。对PPI网络和微阵列数据的系统分析进一步揭示了六个核心目标，包括TNF,IL-1β,IL-6、TP53、VEGFA和PTGS2主要参与流体剪切应力和动脉粥样硬化,脂质和动脉粥样硬化，PI3K-Akt信号通路等。此外，有效化合物的拟议贡献指数表明这些化合物，包括异阿魏酸,槲皮素,calycosin,阿魏酸,山奈酚,calycosin7-O-糖苷，福蒙素,黄芪甲苷和柴胡皂苷D，作为SXD的核心化合物。分子对接结果证实了那些核心化合物-靶标对表现出强结合能。此外，我们验证了SXD可显着减轻CHD大鼠的心肌组织损伤，并通过减少TNF的产生来逆转H/R诱导的H9c2细胞活力降低，IL-6和IL-1β,根据RT-qPCR和Westernblot结果，通过下调TP53，caspase3和细胞色素CmRNA表达水平以及caspase3，caspase9和细胞色素C蛋白表达水平来减少心肌细胞凋亡。我们的发现解释了SXD在CHD治疗中的潜在的药理机制。为今后SXD的基础和临床研究奠定了基础。
