Andrographolide Alleviates Liver Damage Caused by Salmonella in Mice by Inhibiting the PANoptosis Pathway

The emergence of antibiotic resistance in pathogens, including Salmonella typhimurium, poses a major challenge to animal health and safety. Andrographolide is well known for its antibacterial properties and therefore offers potential as an antimicrobial treatment to lessen the damage caused by Salmonella. PANoptosis is defined as an inflammatory coordinated cell death pathway encompassing apoptosis, pyroptosis, and necroptosis. To reduce the organ and tissue damage caused by bacterial infection and reduce antibiotic resistance, this study investigated the effect of andrographolide on liver damage in Salmonella-infected mice. We used a mouse model infected with Salmonella typhimurium for in vivo experiments, which involved the detection of the bacterial load in the liver, liver injury indicators, and expression of related PANoptosis-related genes and proteins. Here, our finding indicated that andrographolide effectively inhibited markers associated with apoptosis, pyroptosis, and necroptosis in mouse hepatocytes, alleviated liver injury and clinical symptoms caused by Salmonella typhimurium in mice, and thus exerted therapeutic effects. In this study, we observed that andrographolide modulated the markers associated with these three pathways, indicating their involvement in PANoptosis. These results suggest that andrographolide significantly relieve Salmonella-induced liver injury by inhibiting PANoptosis, highlighting the potential significance of andrographolide as an effective drug for the treatment of Salmonella.