Betulinic Acid Attenuates Lipopolysaccharide-Induced Kidney Inflammatory Injury by Suppressing PANoptosis in Weaned Piglets

In the intensive livestock farming industry, weaned piglets are highly prone to renal injury triggered by weaning stress, pathogen infection, and antibiotic abuse. This injury induces metabolic disorders and immunosuppression, severely restricting production efficiency. As a natural pentacyclic triterpene, betulinic acid (BA) exhibits notable biological activities, particularly in anti-inflammatory and antioxidant activities. However, its preventive potential against renal injury in piglets and the underlying mechanisms remain unclear. In this study, BA was administered as a long-term dietary pretreatment prior to lipopolysaccharide (LPS) challenge to evaluate its protective role in a preventive model of renal inflammatory injury in weaned piglets. BA pretreatment significantly mitigated pathological lesions, including renal tubular epithelial cell shedding and interstitial congestion, reduced the renal index, and decreased the concentrations of renal injury markers and serum UREA. In addition, BA pretreatment mitigated the renal oxidative stress and inflammatory injury induced by LPS in piglets. Molecular analyses showed that BA pretreatment was associated with decreased expression of key markers involved in apoptosis, necroptosis, and pyroptosis in renal tissue. Furthermore, protein-protein interaction analysis suggested potential associations between the HMGB1/TLR4/NF-κB signaling pathway and PANoptosis-related processes, providing exploratory and hypothesis-generating support for the proposed regulatory network. Collectively, these findings suggest that dietary BA pretreatment exerts a preventive effect against LPS-induced renal inflammatory injury in weaned piglets, potentially through modulation of HMGB1/TLR4/NF-κB-associated PANoptosis-related pathways, providing a theoretical basis for its application in livestock production.