Background: At present, the treatment and prevention of Pasteurella multocida infections in pigs mainly rely on antibiotics and vaccines, but inflammatory injury cannot be eliminated. The compound 18β-glycyrrhetinic acid (GA), a pentacyclic triterpenoid extracted from Glycyrrhiza glabra L. root (liquorice) and with a chemical structure similar to that of steroidal hormones, has become a research focus because of its anti-inflammatory, antiulcer, antimicrobial, antioxidant, immunomodulatory, hepatoprotective and neuroprotective effects, but its potential for the treatment of vascular endothelial inflammatory injury by P. multocida infections has not been evaluated. This study aimed to investigate the effects and mechanisms of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections. Materials and Methods: Putative targets of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections were identified using network pharmacological screening and molecular docking simulation. The cell viability of PIEC cells was investigated via the CCK-8 assay. The mechanism of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections were investigated using cell transfection and western blot. Results: Through network pharmacological screening and molecular docking simulation, this study found that PARP1 may be a core target for GA to exert anti-inflammatory effects. Mechanistically, GA alleviates P. multocida-induced vascular endothelial inflammation by PARP1-mediated NF-κB and HMGB1 signalling suppression. Conclusion: These findings, for the first time, demonstrate the potential therapeutic relationship among GA, PARP1 and inflammatory injury, providing a candidate drug, therapeutic targets and explanation for treating vascular endothelial inflammatory injury caused by P. multocida infection.

Glaesserella parasuis (GPS), a causative agent of Glässer’s disease, is thought to be the main fatal cause of peritonitis in swine, thus resulting in high mortality and morbidity and significant economic losses to the swine industry. However, the mechanisms of GPS infection-induced apoptosis and possible therapeutic pathway for GPS infection in peritonitis remain unclear. Baicalin has important biological functions during disease treatment, such as antiviral, bacterial inhibition, anti-apoptosis, and anti-inflammatory. However, whether baicalin has anti-apoptotic effects during the process of GPS infection in peritonitis is unclear. In the present study, the anti-apoptotic effect and mechanisms of baicalin in GPS infection-induced apoptosis were investigated in porcine peritoneal mesothelial cells (PPMC). The results showed that baicalin could inhibit the apoptosis rate occurrence of PPMC induced by GPS to various degrees and inhibit the expression of apoptosis-related genes and cleaved caspase-3. Meanwhile, baicalin significantly antagonized the expression of p-JNK, p-p38, and p-ERK induced by GPS in PPMC. These findings for the first time demonstrate that baicalin exerted the effect of antagonizing GPS induced apoptosis in PPMC by inhibiting the activation of the PKC-MAPK pathway and could be a therapeutic option in the management of GPS infection.

Aflatoxin B1 (AFB1) is a highly toxic secondary metabolite produced by Aspergillus species. Its extensive contamination of animal feed and human food poses significant health hazards to livestock and humans, with hepatotoxicity being a primary concern. This study investigated the protective effect of baicalin on AFB1-induced liver injury in ducklings. In the first experiment, ducklings were administered AFB1 at doses of 0, 6, 12, or 24 μg/kg body weight/day for 7 days to identify the optimal concentration for establishing a model of AFB1-induced growth performance and liver injury. Administration of AFB1, particularly at the higher doses (12 and 24 μg/kg body weight/day), significantly reduced growth performance and induced structural and functional liver injury (p < 0.05). In a second experiment, ducklings were administered AFB1 (12 μg/kg body weight/day) with or without baicalin (25–100 mg/kg body weight/day) for 7 days. Dietary baicalin significantly increased the serum albumin level; reduced the serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase levels; improved growth performance; and ameliorated structural and functional liver injury in ducklings exposed to AFB1 (p < 0.05). The results indicate that dietary baicalin alleviates AFB1-induced liver injury and growth performance decline in ducklings. Hence, baicalin could serve as a potential feed additive to reduce the harmful effects of AFB1 in the poultry breeding industry.

T-2 toxin, a highly toxic type A trichothecene, is a secondary fungal metabolite produced by various Fusarium species. The consumption of food and feed contaminated with T-2 toxin is a major factor contributing to growth retardation, posing significant risks to both human and animal health. However, the specific targets and mechanisms that mitigate T-2 toxin-induced growth retardation remain unclear. In this study, transcriptomic analysis was employed to identify key differentially expressed genes associated with the alleviation of T-2 toxin-induced growth retardation. Peroxiredoxin 4 (PRDX4), a gene linked to oxidative stress and apoptosis, was found to be one of the most downregulated in T-2 toxin-treated GH3 cells, an in vitro model of growth retardation. The experiments demonstrated that T-2 toxin significantly increased reactive oxygen species’ production, apoptosis, and cell cycle arrest while reducing the activity of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) and PRDX4 expression in GH3 cells. Furthermore, PRDX4 silencing exacerbated T-2 toxin-induced oxidative stress and apoptosis, whereas PRDX4 overexpression effectively mitigated these effects. These findings highlight the protective role of PRDX4 in counteracting T-2 toxin-induced oxidative stress and apoptosis, suggesting that PRDX4 can serve as a therapeutic target for the treatment of T-2 toxin-induced growth retardation.

Streptococcus suis (S. suis) is a major swine pathogen throughout the world as well as an emerging zoonotic agent. Among the symptoms caused by S. suis, including septicemia, pneumonia, endo-carditis, arthritis, and meningitis, the latter is the most overlooked. In the present study, we explored the mechanism of action of berberine against S. suis meningitis by obtaining berberine-related action targets, porcine S. suis meningitis targets, and human S. suis meningitis targets from open databases. We constructed a protein–protein interaction (PPI) network by using the STRING database and employed Cytoscape 3.8.0 to screen for core targets. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses through DAVID. We identified 31 potential targets of berberine, of which Toll-like receptor 4 (TLR4), fibronectin 1 (FN1), superoxide dismutase (SOD1), and catalase (CAT) were the four most critical targets. GO analysis revealed the enrichment of terms related to the response to oxidative stress and the inflammatory response. KEGG analysis revealed the enrichment of the interleukin 17 (IL-17), phosphoinositide 3-kinase (PI3K)-Akt, TLR, tumor necrosis factor (TNF), and mitogen-activated protein kinase (MAPK) signaling pathways. In addition, the admetSAR results showed that berberine can cross the blood–brain barrier. The molecular docking results indicated key binding activity between TLR4–berberine and FN1–berberine. In summary, berberine protects against Streptococcus suis meningitis by regulating inflammatory response and oxidative stress in humans and pigs. Our study updates the current knowledge of the targets of S. suis meningitis to exploit new drugs in humans and pigs, to develop environmentally friendly and antibiotic-free animal-derived food products, and to improve the farming industry and economic development.