目的:利用系统药理学技术,初步探究丹参治疗冠心病的作用机制。方法:通过建立丹参多组分靶点数据集、冠心病靶点数据集,构建丹参治疗冠心病的"成分-靶点-疾病"交互网络,进行可视化分析、网络中各节点的拓扑参数分析,然后采用京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)进行通路注释分析和基因本体(gene ontology,GO)富集分析,预测丹参治疗冠心病的作用机制。结果:系统药理学分析结果显示,共发现32个与疗效直接相关的活性成分以及47个潜在交互作用蛋白,并获得了14条相关信号通路和62个生物过程;丹参多组分所作用的靶点主要富集于磷脂酰肌醇-3-激酶-蛋白激酶B信号通路、叉头转录因子信号通路及丝裂原活化蛋白激酶信号通路等;丹参多成分所作用的靶点主要富集于多个与冠心病有关的生物过程,主要包括调节活性氧代谢过程、正调控平滑肌细胞增殖、雄激素受体信号通路、由p53类介导的DNA损伤反应及积极调节活性氧代谢过程。结论:这些发现初步揭示了丹参治疗冠心病的系统调控网络,为丹参治疗冠心病的研究提供了理论依据。
Objective To explore the active components with toxic effects in five Aconitum L. herbal medicines on Tetrahymena thermophila. Methods The fingerprints of five Aconitum L. herbal medicines were established by ultra-high performance liquid chromatography （UPLC） and the toxicity was evaluated by using a TAM Air Isothermal Calorimeter on Tetrahymena thermophila SB1 10. Results By analyzing the spectrum- effect relationships between UPLC fingerprints and toxic effects, the active components which had the toxic effects were obtained. Conclusion This work provides a general model of the combination of UPLC and microcalorimetry to study the spectrum-effect relationships of the five Aconitum L. herbal medicines, which could be used to evaluate the toxic effects and analyze the principal toxic components of the five Aconitum L. herbal medicines. On the whole, this result provides the experimental basis for the safe use of the five Aconitum L. herbal medicines in clinic.
Objective： To investigate the possible mechanism of San-Cao Granule（SCG, 三草颗粒） mediating antiliver fibrosis. Methods： A total of 60 male Sprague-Dawley rats were randomly divided into the normal control group, porcine serum-treated group, ursodesoxycholic acid（UDCA, 60 mg/kg）, SCG（3.6 g/kg） group, SCG（1.8 g/kg） group and SCG（0.9 g/kg） group, with 10 rats in each group. Liver fibrosis was induced with porcine serum by intraperitoneal injection for 8 weeks, except for the normal control group. Then, the rats in the three SCG-treated groups and UDCA group were administered SCG and UDCA respectively for 4 weeks. The serum levels of alanine transaminase（ALT）, aspartate transaminase（AST）, albumin（ALB）, total bilirubin（TBIL）, hyaluronic acid（HA）, laminin（LN）, and type Ⅳcollagen（ⅣC） were examined using commercial kits and hepatic histopathology was examined with hematoxylin and eosin and Masson staining. Moreover, the protein expression levels of high mobility group box-1 protein（HMGB1）, transforming growth factor β1（TGF-β1）, phosphorylated mothers against decapentaplegic homolog 3（p-Smad3）, Smad7, toll-like receptor 4（TLR4）, myeloid differentiation factor 88（My D88）, nuclear factor-kappa B（NF-κB） and α-smooth muscle actin（α-SMA） were determined by western blot, immunohistochemistry and real time quantitativereverse transcription polymerase. Results： Both SCG（3.6 and 1.8 g/kg） and UDCA significantly ameliorated the liver fibrosis induced by porcine serum as indicated by retarding the serum levels increasing of ALT, AST, TBIL, HA, LN and ⅣC and preventing the serum level reducing of ALB compared with the model group（all P〈0.01）. Meanwhile, the collagen deposition was attenuated by SCG and UDCA treatment. Furthermore, SCG markedly reduced the expressions of HMGB1, TGF-β1, p-Smad3, TLR4, My D88, NF-κB and α-SMA, and enhanced the expression of the Smad7 compared with the model group（all P〈0.01）. Conclusion�
