基于"性-效-物"的小儿消积止咳口服液质量标志物研究OACSTPCD

Objective:To determine the quality markers(Q-marker)in Xiao'er Xiaoji Zhike Oral Liquid(XEXJ)based on the theory of"property-response-component".Methods:The molecular docking experiment was used to determine the drug properties(tastes)of the compounds.Schrödinger 2020 Maestro software was used to conduct molecular docking experiments between sour,sweet,bitter and pungent taste receptors and corresponding compounds.Network pharmacology and in vitro receptor experiments were used to determine the efficacy of compounds.Related databases were used to obtain and integrate the common targets of compounds and diseases,which were input into the STRING network analysis platform to screen out the core targets,and then bioinformatics analysis was performed.Cytoscape was used to construct the network.The effects of the representative components on cholinergic receptor muscarinic 3(CHRM3),adrenergic receptor beta 2(ADRB2),adrenergic receptor alpha 1A(ADRA1A)and cyclooxygenase-2(COX-2)receptors were further detected by G protein-coupled receptor and enzyme activity assay.Results:The results of molecular docking showed that the organic acids and coumarins may be the material basis for the sour taste of XEXJ.The saccharides and the simple phenylpropanoids may be the sweet material basis.The lignans,phenylethanoid glycosides,flavonoids and triterpenoids might be the material basis for the bitter taste.The alkaloids and flavonoids may be the material basis for the pungent taste.The results of network pharmacology showed that XEXJ may exert its pro-digestive,anti-tussive,anti-pyretic and anti-inflammatory effects via 90 pathways,such as neurotransmitter-receptor interactions,serotonergic synapse,cyclic guanosine monophosphate-protein kinase G(cGMP-PKG)signaling pathway,and calcium signaling pathway.The results of functional receptor experiments showed that the mechanism of XEXJ in clearing heat,resolving lung congestion,resolving accumulation and relieving cough may be related to the activation of CHRM3 and ADRB2 receptors and the inhibition of ADRA1A and COX-2 receptors.In conclusion,hesperidin,naringin,neohesperidin,demethylnobiletin,synephrine,arecoline,quercetin-3-O-β-D-glucose-7-O-β-D-gentiobioside,quercitrin,isoquercitrin,hyperoside,kaempferol,forsythoside A,forsythoside E,phillygenin,(+)-piresil-4-O-β-D-glucopyraside,platycodin D,3,29-dibenzoyl rarounitriol,citric acid and chlorogenic acid might be the quality markers of XEXJ.Conclusion:Based on the theory of"property-response-component",the quality markers of pharmacodynamic action of XEXJ were preliminarily determined by molecular docking,network pharmacology and receptor experiments,providing a reference for the quality control and mechanism research of XEXJ.