Laiyang pear cough syrup relieves cough through the PI3K-AKT pathway

Abstract

Objective

To predict the mechanism of action of Laiyang Pear Cough Syrup in treating cough by using network pharmacology, molecular docking technology and the predicted key pathways in animal experiments.

Methods

Chemical components of each medicinal flavor were collected and screened from TCMSP and other databases to establish a database of the components of Laiyang Pear Cough Syrup. Cough-related targets were obtained from TTD and other databases. A Venn diagram of the components targets and cough targets was drawn to prelim determine the potential targets of the active ingredients of Laiyang Pear Cough Syrup in the treatment of cough. A PPI network was constructed and key targets were screened. The data were into Cytoscape 3.10.1 software, and a "active component-disease target" network was constructed, and key components were screened. The screened targets were subjected to GO enrichment analysis and KEGG pathway enrichment analysis. Molecular docking verification between key targets and core active ingredients was conducted using AutoDock Tools 1.5.6 software. A citric acid-induced guinea pig cough model was established. The cough latency and cough frequency were measured in the control and treatment groups, and the PI3K-AKT pathway predicted by network pharmacology was validated via Western blot analysis.

Results

43 active chemical components, 76 common targets, 591 GO biological processes, and 159 KEGG signaling pathways were screened out. The active components of Laiyang Pear Cough Syrup in the treatment of cough may be quercetin, stigmasterol, and luteolin, and the key may be IL-6, TNF, AKT1, IL-1β, and PTGS₂, which mainly regulate the PI3K/AKT pathway to relieve cough. Molecular docking revealed that luteolin, quercetin, and stigmasterol as the key active ingredients in Laiyang Pear Cough Syrup bind to AKT1 with high affinities, displaying docking scores of −8.1, −8.0, and −7.7 kcal mol⁻¹. These results indicate that the compounds may function as potent agonists to activate the PI3K-AKT signaling pathway. Laiyang Pear Cough Syrup can significantly prolong the cough latency period and reduce the number of coughs (compared with the control group, P < 0.01 or 0.05), and down-regulate the expression of PI3K, p-PI3K, AKT, p-AKT proteins.

Conclusion

Laiyang Pear Cough Syrup can relieve cough through a variety of components, targets and pathways. Regulating the PI3K-AKT pathway may be its main mechanism of action.