[Prediction of mechanism of ginger-processed Anemarrhenae Rhizoma in intervening in cough due to cold and dampness in lung based on network pharmacology]

This study employed network pharmacology, molecular docking, and animal experiments to investigate the mechanism of ginger-processed Anemarrhenae Rhizoma in treating cough due to cold and dampness in lung, aiming to provide a modern pharmacological basis for this therapy. The active ingredients of ginger-processed Anemarrhenae Rhizoma were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) with the oral bioavailability(OB≥30%) and drug likeness(DL≥0.18) as the screening conditions and from the relevant literature. A library of the active ingredients of ginger-processed Anemarrhenae Rhizoma was established, and SwissTargetPrediction was used to predict the potential targets of the active ingredients. The western medical symptom corresponding to cough due to cold and dampness in lung was identified as acute bronchitis based on SymMap, and the targets related to acute bronchitis were obtained from GeneCards, and the Online Mendelian Inheritance in Man(OMIM). Venny was utilized to obtain the common targets between the active ingredients and the disease, and STRING and Cytoscape were used to establish the protein-protein interaction(PPI) network for the common targets. The Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of potential therapeutic targets were performed with DAVID. AutoDock was used to simulate the molecular docking between the active ingredients with potential targets. Finally, a mouse model of acute bronchitis was prepared with the smoke plus cold stimulation method for validation. In this study, a total of 557 potential targets of the active ingredients of ginger-processed Anemarrhenae Rhizoma were retrieved, including 157 common targets shared with acute bronchitis. The enrichment analysis yielded 1 072 GO terms and 169 KEGG pathways. The results of molecular docking showed that the active ingredients had good binding affinity with MAPK14 and MMP3, and timosaponin AⅢ showcased the strongest binding affinity among the active ingredients. In the animal experiments, other treatment groups except the low-and high-dose raw Anemarrhenae Rhizoma and the ginger decoction groups showed reduced pathological changes in the lung tissue, attenuated inflammatory cell infiltration, lowered levels of interleukin(IL)-1β, IL-18, and tumor necrosis factor(TNF)-α in the bronchoalveolar lavage fluid(BALF), and down-regulated mRNA and protein levels of MAPK14 and MMP3 in the lung tissue. Moreover, ginger-processed Anemarrhenae Rhizoma outperformed raw Anemarrhenae Rhizoma. This study preliminarily revealed that ginger-processed Anemarrhenae Rhizoma can inhibit inflammation by regulating the IL-17, TNF, and other signaling pathways to treat cough due to cold and dampness in lung, verifying the rationality of this therapy. The findings provide a basis for the inheritance and application of the characteristic ginger processing of Anemarrhenae Rhizoma.