联合体内外多维化学物质组和分子对接策略的炮附子抗炎药效物质基础研究

Study on pharmacodynamic material basis of processed Aconiti Lateralis Radix Praeparata combined with in vivo and in vitro multi-dimensional chemical substance group and molecular docking strategy

目的挖掘炮附子Aconiti Lateralis Radix Praeparata潜在的抗炎药效物质基础。方法采用超高效液相色谱-质谱联用法(UPLC-MS)鉴别炮附子的体内外多维化学物质组;通过蛋白互作网络、拓扑学分析以及相关文献筛选疾病靶点并结合分子对接技术筛选与目标蛋白结合良好的化合物。结果鉴定了炮附子中53个化学成分、37个入血成分;确定Toll样受体4(Toll-like receptor 4,TLR4)、基质金属蛋白酶9(matrix metalloprotein 9,MMP9)受体、纤溶酶原(plasminogen,PLG)受体为关键靶蛋白,发现卡拉可林、宋果灵、海替生、易混翠雀花碱、黄草乌碱丁、绣线菊碱C、苯甲酰新乌头原碱、苯甲酰乌头原碱、苯甲酰次乌头原碱、三小叶翠雀碱E、裸翠雀亭等21个化合物为炮附子潜在的抗炎药效物质。结论所建立的方法充分考虑中药饮片化学成分的复杂性,从多个层次逐步推进,方便快捷地筛选出炮附子潜在的抗炎药效物质,可为中药药效物质筛选提供借鉴。

Objective To excavate the potential anti-inflammatory pharmacodynamic material basis of processed Aconiti Lateralis Radix Praeparata(Pao Fuzi in Chinese).Methods Ultra-performance liquid chromatography-mass spectrometry(UPLC-MS)was used to identify the multi-dimensional chemical substance group of Aconiti Lateralis Radix Praeparata in vivo and in vitro;Protein interaction network,topological analysis and related literatures were used to screen disease targets,and then molecular docking technology was used to screen for compounds that bind well to the target proteins.Results A total of 53 chemical components of Aconiti Lateralis Radix Praeparata and 37 components that enter the blood were identified;TLR4 receptor,MMP9 receptor,and PLG receptor were identified as the key target proteins,and 21 compounds such as karakoline,songorine,hetisine,condelphine,sachaconitine,spiradine C,benzoylmesaconine,benzoylaconine,benzoylhypacoitine,trifoliolasine E,and denudatine were found to be the potential anti-inflammatory pharmacodynamic materials.Conclusion The established method fully considered the complexity of the chemical components of traditional Chinese medicine decoction pieces and advanced from multiple levels gradually.It is convenient and quick to screen out the potential anti-inflammatory pharmacodynamic material of Aconiti Lateralis Radix Praeparata.The idea can provide a reference for the screening of pharmacodynamic material of Chinese medicine.