Effects of fisetin on virulence of Actinobacillus Pleuropneumoniae.

Porcine infectious pleuropneumonia (PCP), caused by Actinobacillus pleuropneumoniae (APP), is a highly infectious respiratory disease of pigs, resulting in significant economic losses to the industry. Apx toxins are cytolytic virulence factors produced by APP. The natural flavonoid fisetin has a variety of biological activities, including antioxidant and anti-inflammatory properties. This study aimed to investigate the protective effects of fisetin against APP. Fisetin was found to effectively inhibit the hemolytic activity of both APP culture supernatants and the purified toxins, and blood agar plate results also showed that the addition of fisetin to APP reduced the diameter of the hemolytic zone. Fisetin did not influence the expression of Apx toxins, although it reduced that of the virulence factor CPS. In vitro, fisetin effectively inhibited APP cytotoxicity and intracellular colonization, as well as intracellular ROS production. Furthermore, it reduced the expression of IL-6, TNF-α, and TLR4 in porcine alveolar macrophages (3D4/21). In vivo, fisetin reduced APP colonization of mouse lung tissues and improved the survival rate of APP-infected mice. In conclusion, fisetin was found to reduce the release of pro-inflammatory cytokines and ROS, decrease the risk of hemolysis, and attenuate APP virulence. The findings highlight the potential therapeutic value of fisetin in the management of APP infection. Further investigations into the mechanisms underlying the effects of fisetin are warranted.