Magnolol ameliorates Streptococcus suis serotype 2-induced pulmonary inflammatory injury in mice via inhibition of GSDMD

Streptococcus suis serotype 2 (SS2) is a highly virulent zoonotic pathogen that causes substantial economic losses in the swine industry and poses a serious threat to public health. Magnolol, a key bioactive compound derived from Magnolia officinalis, is known for its anti-inflammatory and Antibacterial properties, yet its specific impact on SS2-induced inflammatory injury has not been fully elucidated. This study aimed to elucidate the protective mechanisms of magnolol against SS2 Infection. We initially demonstrated that SS2 Infection induces severe pulmonary inflammation in mice, characterized by alveolar wall thickening, tissue congestion, and increased secretion of the pro-inflammatory cytokines IL-1β and IL-18. Treatment with magnolol significantly alleviated these pathological changes, reduced lung tissue damage, and decreased cytokine release. In vitro experiments further revealed that magnolol attenuated SS2-induced macrophage membrane disruption, as indicated by decreased propidium iodide (PI) uptake, and inhibited the production of IL-1β and IL-18. Mechanistic investigations using Western blot analysis confirmed that magnolol reduced the expression of GSDMD. Correspondingly, GSDMD-deficient mice exhibited reduced Bacterial loads in multiple tissues, diminished lung inflammation, downregulated expression of IL-1β and IL-18, enhanced macrophage recruitment, and decreased macrophage death-effects that closely mirrored those achieved with magnolol treatment. Collectively, these findings demonstrate that magnolol alleviates SS2-induced inflammatory injury by inhibiting GSDMD, underscoring its potential as a host-directed therapeutic agent for the management of streptococcal infections.