Objective To establish an HPLC analysis method for simultaneous determination of multiple components in Kelu oral liquid and to investigate its antitussive mechanism based on network pharmacology.

Methods An HPLC method was developed to simultaneously determine the content of nine components (two ephedrine alkaloids and seven flavonoids) derived from three medicinal materials ( Ephedra sinica, Licorice and Scutellaria baicalensis ) in Kelu oral liquid, and the transfer rate was investigated. Potential targets of the active ingredients in Kelu oral liquid associated with diseases were screened using the Swiss Target Prediction and TTD databases. A "drug-ingredient-target-disease" network was constructed, and GO functional annotation and KEGG pathway enrichment analyses were performed.

Results The established HPLC method allowed for the simultaneous determination of all nine components. Methodological validation results were satisfactory, with no interference observed between the components. The diversion rate of oroxylin A-7-O-β-D-glucuronide from the raw materials to the preparation was the highest (67.42 %), while the diversion rates of baicalin, baicalein, liquiritin apioside, and wogonin were all below 20 %. Network pharmacological analysis identified key active ingredients such as quercetin, luteolin, kaempferol, and wogonin. These components are likely to exert antitussive effects by acting on core targets including tumor suppressor protein 53 (TP53), protein kinase Bα (AKT1), tumor necrosis factor (TNF), signal transducer and activator of transcription 3 (STAT3), thereby regulating signaling pathways such as interleukin-17 signaling pathway and Th17 cell differentiation.

Conclusion The developed analytical method is stable, reliable, and suitable for the quality control of Kelu oral liquid. The antitussive effect of the preparation involves multiple components, targets, and pathways, providing a foundation for further in-depth investigation of its mechanism and clinical development.

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