Integrated metabolomics and network pharmacology to reveal the different reason of propolis and gum against bacterial infection

Background Propolis is a substance derived from plant resin (tree gum), and its antibacterial activity is one of its most important biological activities. However, the key differential components between propolis and tree gum and their antibacterial mechanisms remain unclear. Therefore, this study aimed to reveal the key active differential metabolites and potential antibacterial mechanisms of these differential metabolites utilizing widely targeted metabolomics and network pharmacology. Methods Widely targeted metabolomics was employed to identify metabolites in poplar propolis and poplar gum. The antibacterial activities of poplar propolis and poplar gum against methicillin-resistant Staphylococcus aureus (MRSA) were compared using the inhibition zone diameter (DIZ), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC), and the data were analyzed using one-way analysis of variance (ANOVA). Additionally, network pharmacology was utilized to screen key active differential metabolites and their core targets. The potential antibacterial mechanisms of these key active differential metabolites were determined through GO enrichment and KEGG pathway analysis. Results Using widely targeted metabolomics, we identified 1646 metabolites in two poplar propolis samples and one poplar gum sample, of which 942 were common differential metabolites that were enriched in nine KEGG enrichment pathways, including flavonoid biosynthesis. In vitro antibacterial experiments also revealed that the diameter of the zone of inhibition of MRSA by poplar gum was significantly different from that of poplar propolis (p < 0.05). Furthermore, the MIC for poplar propolis was 0.15625 mg/ml, the MBC was 0.3125 mg/ml, the MIC for poplar gum was 0.3125 mg/ml, and the MBC was 0.625 mg/ml. Poplar propolis exhibited stronger antibacterial activity than poplar gum. Subsequently, network pharmacology analysis identified 72 key active differential metabolites and 23 core targets associated with the treatment of bacterial infection. Finally, GO enrichment and KEGG pathway analyses revealed that the core targets were predominantly enriched in signaling pathways related to immune regulation and the inflammatory response. Conclusions In summary, although propolis is derived from tree gum, its metabolites are significantly different from those of tree propolis. In addition, the key active differential metabolites of propolis and poplar propolis determined the differences in their antibacterial efficacy, and the potential antibacterial mechanisms of poplar propolis and poplar gum might include immune regulation and the inflammatory response. Moreover, the screening of key active differential metabolites might lead to the identification of reliable biomarkers for poplar propolis and poplar gum. This work provides valuable insights for future quality control of poplar propolis and treatment of associated bacterial infections.