Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210046, China.
Evid Based Complement Alternat Med. 2013;2013:901943. doi: 10.1155/2013/901943. Epub 2013 Oct 21.
In this study, the reverse docking methodology was applied to predict the action targets and pathways of Shaofu Zhuyu decoction (SFZYD) bioactive ingredients. Furthermore, Traditional Chinese Medicine (TCM) cold coagulation blood stasis (CCBS) syndrome was induced in female Sprague-Dawley rats with an ice-water bath and epinephrine, and SFZYD was used to treat CCBS syndrome. A metabolomic approach was used to evaluate changes in the metabolic profiles and to analyze the pharmacological mechanism of SFZYD actions. Twenty-three potential protein targets and 15 pathways were discovered, respectively; among these, pathways are associated with inflammation and immunological stress, hormone metabolism, coagulation function, and glycometabolism. There were also changes in the levels of endogenous metabolites of LysoPCs and glucuronides. Twenty endogenous metabolites were identified. Furthermore, the relative quantities of 6 endogenous metabolites in the plasma and 5 in the urine were significantly affected by SFZYD (P < 0.05). The pharmacological mechanism of SFZYD was partially associated with glycerophospholipid metabolism and pentose and glucuronate interconversions. In conclusion, our findings demonstrated that TCM CCBS pattern induced by ice water and epinephrine was complex and related to multiple metabolic pathways. SFZYD did regulate the TCM CCBS by multitargets, and biomarkers and SFZYD should be used for the clinical treatment of CCBS syndrome.
在这项研究中，应用反向对接方法预测了芍药逐瘀汤（SFZYD）生物活性成分的作用靶点和途径。此外，采用冰水浴和肾上腺素诱导雌性 Sprague-Dawley 大鼠产生中医寒凝血瘀（CCBS）综合征，并使用 SFZYD 治疗 CCBS 综合征。采用代谢组学方法评估代谢谱的变化，并分析 SFZYD 作用的药理机制。分别发现了 23 个潜在的蛋白质靶点和 15 条途径；其中，这些途径与炎症和免疫应激、激素代谢、凝血功能和糖代谢有关。LysoPCs 和葡糖醛酸苷的内源性代谢物水平也发生了变化。鉴定出 20 种内源性代谢物。此外，SFZYD 显著影响了血浆中的 6 种内源性代谢物和尿液中的 5 种内源性代谢物的相对含量（P<0.05）。SFZYD 的药理机制部分与甘油磷脂代谢和戊糖和葡糖醛酸相互转化有关。总之，我们的研究结果表明，冰水和肾上腺素诱导的中医 CCBS 模式复杂，与多种代谢途径有关。SFZYD 通过多靶点调节中医 CCBS，生物标志物和 SFZYD 应用于 CCBS 综合征的临床治疗。
