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

## TL;DR

Betulinic acid, a plant compound, helps protect piglet kidneys from inflammation and damage caused by bacterial toxins.

## Contribution

This study reveals betulinic acid's novel preventive role in reducing kidney injury in piglets via suppression of PANoptosis.

## Key findings

- Betulinic acid pretreatment reduced kidney tissue damage and inflammation in piglets exposed to bacterial toxins.
- The compound improved antioxidant capacity and modulated HMGB1/TLR4/NF-κB signaling pathways.
- Molecular analyses showed decreased expression of cell death markers like apoptosis and pyroptosis.

## Abstract

Kidney injury is a common health problem in weaned piglets raised under intensive farming conditions and is often associated with stress, bacterial infection, and inflammation. Such injury can negatively affect animal health and growth performance. Betulinic acid is a natural compound derived from plants and is known for its anti-inflammatory and antioxidant properties. However, its potential role in protecting kidney health in piglets has not been fully explored. In this study, piglets were fed a diet supplemented with betulinic acid for several weeks before being exposed to a bacterial toxin that induces kidney inflammation. The results showed that dietary pretreatment with betulinic acid reduced kidney tissue damage, improved antioxidant capacity, and alleviated inflammatory responses. Changes in several molecular indicators related to cell injury and inflammation were also observed, suggesting that betulinic acid may help regulate multiple biological processes involved in kidney damage. Overall, these findings indicate that long-term dietary supplementation with betulinic acid may help reduce inflammation-related kidney injury in piglets. This study provides useful information for improving animal health management and suggests a potential application of natural plant-derived compounds in livestock production.

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.