The Effects of Baitouweng Decoction on Salmonella Typhimurium Infection and Its Underlying Mechanisms Evaluated by In Vivo and In Vitro Experiments, Network Pharmacology Analysis, and Molecular Docking Technology.

Abstract

Salmonella Typhimurium is a foodborne pathogen threatening livestock and human health. It is highly resistant to commonly used clinical antibiotics, and it is urgently needed to explore new anti-Salmonella treatment schemes. In this study, first, our in vivo mouse experiments showed that Baitouweng decoction (BTW), a classical Traditional Chinese Medicine (TCM) prescription, had good efficacy against Salmonella Typhimurium infection: mitigating weight loss of mice; lowering the bacterial load of liver, spleen, and colon; reducing the production of serum inflammatory factors (interleukin-1β and tumor necrosis factor-α); and decreasing histological index scores than that in the Salmonella Typhimurium infection group. Furthermore, we explored the potential active components and molecular mechanism of BTW in the treatment of Salmonella Typhimurium infection. A total of 465 compounds of BTW were retrieved from herb website and 227 bioactive compounds were identified, 911 potential BTW-related targets and 1,602 disease targets of Salmonella Typhimurium infection were acquired by ten public analytical databases, among them, 188 genes were overlay targets of BTW-Salmonella Typhimurium; String, Metascape, and Cytoscape plug-in Molecular Complex Detection and ClueGo analysis pointed that BTW exerted an anti-Salmonella effect through a multicomponent, multitarget, and multipathway manner, including 10 hub targets (TNF, AKT CASP3, ALB, EGFR, JUN, MAPK, STAT3, VEGFA, and TP53) and 94 pathways such as cell apoptosis, inflammation, and metabolism. Finally, AutoDock Vina showed that the hub target AKT1 with menispermine and quercetin had good binding energy, which was confirmed by the in vitro cellular thermal shift assay and drug affinity responsive target stability assay. This study laid the foundation for further study of BTW mechanism and for further development of BTW anti-Salmonella.