Diosmetin Alleviates MRSA-Induced Pneumonia in Mice by Inhibiting NLRP3 Inflammasome Activation and NF-κB Signaling Pathway.

Background/

Objectives

Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant pathogen that poses a major public health concern. It predominantly infects immunocompromised individuals and is frequently associated with severe pulmonary complications, including acute lung injury. Diosmetin, a natural flavonoid, known for its anti-inflammatory, antioxidant, and anti-infective properties. Nevertheless, its therapeutic mechanism in the treatment of acute pneumonia induced by MRSA remains unclear.

Methods

In this study, we employed network pharmacology and molecular docking to elucidate the mechanisms underlying the therapeutic effect of diosmetin against MRSA-induced pneumonia. An MRSA pneumonia model was established in Balb/c mice. The impacts of diosmetin on murine pneumonia were evaluated by detecting biochemical indicators via HE staining, ELISA, RT-qPCR, and WB. In vitro experiments utilized RAW264.7 macrophages to establish an MRSA infection model for further validation of the therapeutic mechanisms of diosmetin.

Results

In vivo results demonstrated that diosmetin alleviated MRSA-induced lung injury and reduced mortality by inhibiting the release of pro-inflammatory cytokines. Furthermore, compared with model mice, diosmetin-treated mice showed reduced phosphorylation levels of NLRP3, pro-caspase-1, ASC, and NF-κB p65, along with an increased level of IκBα in lung tissue. In vitro experiments indicated that diosmetin effectively reduced the levels of pro-inflammatory cytokines in MRSA-infected RAW264.7 macrophages and exerted anti-inflammatory effects by modulating the expression of NLRP3, pro-caspase-1, ASC, IκBα, and NF-κB p65.

Conclusions

Our results demonstrate that diosmetin alleviates MRSA-induced pneumonia in mice, and this protective effect is achieved through dual inhibition of the NF-κB/NLRP3 inflammasome axis.