Molecular mechanism of Dang-Shen-Yu-Xing decoction againstpneumonia based on network pharmacology, molecular docking, molecular dynamics simulations and experimental verification.

Abstract

pneumonia is a highly contagious respiratory infection caused by. It is particularly prevalent in calves, posing a significant threat to animal health and leading to substantial economic losses. Dang-Shen-Yu-Xing decoction is often used to treat this condition in veterinary clinics. It exhibits robust anti-inflammatory effects and can alleviate pulmonary fibrosis. However, its mechanism of action remains unclear. Therefore, this study aimed to preliminarily explore the molecular mechanism of Dang-Shen-Yu-Xing decoction for treatingpneumonia in calves through a combination of network pharmacology, molecular docking, molecular dynamics simulation methods, and experimental validation. The active components and related targets of Dang-Shen-Yu-Xing decoction were extracted from several public databases. Additionally, complex interactions between drugs and targets were explored through network topology, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Subsequently, the binding affinity of drug to disease-related targets was verified through molecular docking and molecular dynamics simulation. Finally, the pharmacodynamics were verified via animal experiments. The primary network topology analysis revealed two core targets and 10 key active components of Dang-Shen-Yu-Xing decoction againstpneumonia. Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that the mechanism of Dang-Shen-Yu-Xing decoction for treatingpneumonia involved multiple signaling pathways, with the main pathways including PI3K-Akt and IL17 signaling pathways. Moreover, molecular docking predicted the binding affinity and conformation of the core targets of Dang-Shen-Yu-Xing decoction, IL6, and IL10, with the associated main active ingredients. The results showed a strong binding of the active ingredients to the hub target. Further, molecular docking dynamics simulation revealed three key active components of IL10 induced by Dang-Shen-Yu-Xing decoction againstpneumonia. Finally, animal experiments confirmed Dang-Shen-Yu-Xing decoction pharmacodynamics, suggesting that it holds potential as an alternative therapy for treatingpneumonia.