<i>In vitro</i> and <i>in vivo</i> antimicrobial activity of protoberberine alkaloids as novel therapeutic candidates against <i>Mycoplasma hyopneumoniae</i>

Swine enzootic pneumonia, caused by <i>Mycoplasma hyopneumoniae</i> (<i>M. hyopneumoniae</i>), remains one of the most economically devastating respiratory diseases in the global swine industry. The emergence of antibiotic resistance in livestock highlights the urgent need for effective, safe, and sustainable alternatives. This study demonstrates that naturally derived protoberberine alkaloids exhibit potent antibacterial activity against <i>M. hyopneumoniae</i> while maintaining low host cytotoxicity and strong anti-inflammatory effects. Among them, jatrorrhizine showed remarkable therapeutic efficacy in infected pigs, comparable with that of florfenicol. These findings provide a scientific basis for developing protoberberine alkaloids as promising natural alternatives to conventional antibiotics for controlling <i>M. hyopneumoniae</i> infections, thereby contributing to improved animal health, reduced antimicrobial resistance, and sustainable swine production.