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目的:筛选抗急性髓系白血病(AML)中药活性分子。方法:搜集治疗急白草药及化合物,通过系统药理学方法预测药物成药性质,潜在靶点以及潜在巯基消耗特性。选择口服生物利用度、类药性和巯基消耗活性较高的紫草素作为验证分子。构建潜在活性化合物-靶点、靶点-疾病网络,通过拓扑学特性筛选关键靶点及潜在活性分子。利用谷胱甘肽(glutathione,GSH)试剂盒及邻苯二甲醛(OPA)荧光法检测加入紫草素后还原型GSH含量变化。数字表达谱芯片检测紫草素100μg·L-1处理HL-60细胞48 h后基因表达。结果:在治疗AML的40味草药的4 024个化合物中,经过口服生物利用度(OB),类药性(drug-likeness,DL)及巯基消耗特性筛选获得72个分子,最后通过与AML相关靶点联系筛选出10个潜在活性化合物。实验验证紫草素消耗细胞及化学体系内GSH,预测靶点能够调控基因芯片的差异基因(100μg·L-1,48 h)。结论:本方法可用于研究中药的物质基础,有助于挖掘治疗AML中药活性分子,为抗AML药物研究提供借鉴。
Objective: To screen anti-acute myeloid leukemia (AML) Chinese medicine active molecules. Methods: Therapies of acute herbs and compounds were collected and systematically predicted the properties of potential drugs, potential targets and the potential of sulfhydryl consumption by systemic pharmacology. Shikonin with oral bioavailability, drug-like properties and high sulfhydryl consumption activity was selected as the verification molecule. Construction of potential active compounds - target, target - disease network, through the topological characteristics of screening key targets and potential active molecules. Glutathione (GSH) kit and phthalaldehyde (OPA) fluorescence were used to detect the content of reduced GSH after adding shikonin. The gene expression of HL-60 cells treated with shikonin 100μg · L-1 for 48 h was detected by digital expression profiling. Results: Forty molecules of 4024 herbs in AML treated with 40 herbal medicines were screened for 72 biomarkers by their oral bioavailability (OB), drug-likeness (DL) and sulfhydryl consumption characteristics. Finally, Contact to screen out 10 potentially active compounds. Experiments show that shikonin consumes cells and chemical GSH, and the predicted target can regulate gene chip differential gene (100μg · L -1,48 h). Conclusion: This method can be used to study the material basis of traditional Chinese medicine and help to excavate the active molecules of traditional Chinese medicine AML, providing reference for anti-AML drug research.