Unveiling the anti-inflammatory power of star anise-cinnamon compound essential oil against MDR Salmonella.

INTRODUCTION: This study aimed to investigate the antiinfi ammatory effects and potential molecular mechanisms of star anise-cinnamon compound essential oil (SCEO) against multidrug-resistant Salmonella Thompson (MDR S. Thompson) infection in mice.

METHODS: An intestinal infection model was established in mice by oral gavage of MDR S. Thompson (1×109 CFU/mL) for two consecutive days. Experimental animals were randomly assigned to a blank group, a model group, a levofioxacin group (positive control), and SCEO low-, medium-, and high-dose groups (100, 200, and 400mg/kg, respectively).

RESULTS AND DISCUSSION: SCEO intervention significantly alleviated clinical symptoms in infected mice, restored pathological damage in the liver and ileum, and normalized the liver index. Gas chromatography-mass spectrom- etry (GC-MS) analysis identified trans-cinnamaldehyde and trans-anethole as the primary active components of SCEO. Network pharmacology and molecular docking analyses revealed strong binding affinities between these components and Toll-like receptor 4 (TLR4), RELA, and mitogen-activated protein kinase 14 (MAPK14) (Vina score < -5.0 kcal/mol). Further in vivo and in vitro experiments demonstrated that SCEO significantly downregulated the mRNA expression of key cytokines, including Tlr4, interleukin-6 (Il6), tumor necrosis factor (Tnf), and interleukin-17A (Il17a), and suppressed the overactivation of the TLR4/nuclear factor kappa-B (NFĸB)/MAPK signaling pathway. SCEO effectively alleviated Salmonella-induced infiammatory damage, a protective process potentially me- diated through the modulation of the TLR4/NFĸB/MAPK signaling axis. These findings provide a theoretical basis for the development of SCEO as a natural, plant-derived anti-infective agent.