Anti-inflammatory effects of Chinese propolis extract on methicillin-resistant Staphylococcus aureus-induced inflammation via modulation of arachidonic acid metabolism

Chinese propolis (CP), a polyphenol-rich functional food, exhibits potent anti-inflammatory activity. However, research on the mechanisms by which it affects inflammatory infections associated with antibiotic-resistant bacteria remains limited. This study investigated the protective role of CP supplementation against inflammation associated with methicillin-resistant Staphylococcus aureus (MRSA) and explored the underlying mechanisms. Anti-inflammatory effects were assessed both in vitro using RAW264.7 macrophages and in vivo using a mouse model of acute lung inflammation induced by heat-inactivated MRSA. Additionally, lipoteichoic acid (LTA), a key MRSA-derived virulence factor, was used to stimulate macrophages for mechanistic evaluation. CP significantly reduced nitric oxide (NO) production and downregulated the mRNA expression of inflammatory mediators in MRSA-stimulated macrophages. In vivo, CP supplementation alleviated pulmonary inflammation in mice by reducing inflammatory cell infiltration in lung tissues and downregulating the gene expression of inflammation-related cytokines. Comparable protective effects were observed in the LTA-induced cell model. CP also decreased reactive oxygen species (ROS) levels and inhibited the expression of key proteins associated with MAPK and NF-κB signaling pathways. Untargeted metabolomic and ELISA analyses revealed that CP primarily suppresses LTB₄, a key metabolite in the 5-LOX branch of arachidonic acid metabolism. Finally, molecular docking analysis identified chrysin, quercetin and pinocembrin as the key constituents in CP responsible for its anti-MRSA associated inflammation activity. These findings suggest that regular dietary intake of CP may help prevent or alleviate inflammation associated with antibiotic-resistant bacterial infections, supporting its potential as a natural dietary intervention.