基于"网络药理学-文本挖掘-分子对接"的补阳还五汤抗动脉粥样硬化"药代效应标志物"研究OA

This study integrated network pharmacology,text mining,and molecular docking to identify core bioactive components of Buyang Huanwu Decoction(BYHWD)against atherosclerosis(AS)and investigate their pharmacokinetic profiles in normal rats and the rat model of lipopolysaccharide(LPS)-induced chronic inflammation.Network pharmacology screening revealed 31 core components and 6 key targets(ESR1,PARP1,ALOX5,CNR2,NOS2,and PTGS2),enabling the construction of a herb-active component-target network for the anti-AS effects of BYHWD.Text mining supplemented high-frequency components reported in the literature,ultimately defining 8 critical pharmacokinetic effect markers:hydroxysafflor yellow A,amygdalin,albiflorin,paeoniflorin,ferulic acid,astragaloside Ⅳ,n-butylidenephthalide,and Z-ligustilide.Molecular docking demonstrated the binding energy below-5 kJ·mol-1 for all component-target pairs except hydroxysafflor yellow A-CNR2,indicating strong biological affinity.In the pharmacokinetic study,normal and model rats were administrated with BYHWD at a dose of 30 g·kg-1 by gavage.Then,plasma samples were collected at multiple time points and detected by the ultra performance liquid chromatography-triple quadrupole-mass spectrometry(UPLC-QQQ-MS)system.The results showed that compared with the normal group,the model group presented decreases in Cmax and AUC0-t and increases in t1/2,CL,and MRT0-t of most components(P<0.05).The tmax of 6 components showed a prolonged trend in the model group.Neither n-butylidenephthalide nor Z-ligustilide was detected in plasma samples due to concentrations below the lower limits of quantification(LLOQ).This multidimensional approach systematically elucidated the anti-AS pharmacodynamic basis and mechanism of BYHWD,establishing a novel methodology for investigating"pharmacokinetic effect markers"in TCM formulas.