18β-Glycyrrhetinic Acid Attenuates Pasteurella multocida-Induced Vascular Injury via Inhibition of PARP1/NF-κB p65 Nuclear Translocation.

Pasteurella multocida (Pm) is a zoonotic pathogen that causes severe hemorrhagic pneumonia in pigs, characterized by vascular injury and systemic inflammatory responses. Our previous studies demonstrated that 18β-glycyrrhetinic acid (GA), a bioactive triterpenoid derived from liquorice, protected against Pm-induced vascular inflammatory injury through suppression of poly(ADP-ribose) polymerase 1 (PARP1)-mediated nuclear factor-kappa B (NF-κB) and high mobility group box 1 (HMGB1) signaling. However, whether GA modulates PARP1-mediated NF-κB p65 nuclear translocation, a critical step in NF-κB activation, remains unclear. This study evaluated the protective effects of GA and its underlying mechanism using a Pm-infected mouse model and immunofluorescence staining of porcine iliac artery endothelial cells. Our results demonstrated that GA treatment attenuated body weight loss, ameliorated hematological and biochemical parameters, and reduced vascular structural damage in Pm-infected mice. Mechanistically, Pm infection induced PARP1 upregulation, accompanied by phospho-p65 (p-p65) nuclear translocation, all of which were suppressed by GA. PARP1 overexpression drove p-p65 nuclear accumulation, which was reversed by GA, whereas PARP1 knockdown suppressed Pm-induced p-p65 nuclear translocation. The findings demonstrated that GA protected against Pm-induced vascular injury by inhibiting PARP1-mediated NF-κB p65 nuclear translocation, supporting its potential as a candidate therapeutic agent for Pm-associated vascular injury.