Berberine Protects Brain Endothelial Barrier via β-Catenin: A Network Pharmacology in Pigs and In Vitro Mechanistic Analysis.
- 1Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China.
- 2Wuhan Engineering and Technology Research Center of Animal Disease-Resistant Nutrition, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China.
Abstract
Glaesserella parasuis (G. parasuis) is an important swine pathogen that causes Glässer's disease, of which meningitis is among the most severe clinical symptoms. However, the molecular mechanisms underlying G. parasuis-induced meningitis remain poorly understood. In this study, we employed a network pharmacology-based strategy combined with in vitro experimental validation to investigate the protective effects and mechanisms of berberine against G. parasuis meningitis. Network pharmacology analysis identified CTNNB1 (encodes the β-catenin protein) as a core target among multiple candidate targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the predicted targets of berberine are significantly associated with inflammatory signaling (mitogen-activated protein kinase MAPK/nuclear factor kappa B NF-κB) and stress-response pathways (forkhead box O FoxO/p53), suggesting a multifaceted protective mechanism against G. parasuis-induced blood-brain barrier (BBB) disruption. Molecular docking results combined with drug affinity responsive target stability (DARTS) assays demonstrated that berberine binds directly to β-catenin with high affinity (docking score = -7.52 kcal/mol), as evidenced by enhanced proteolytic stability of β-catenin upon berberine (2.5, 10, and 20 μg/mL) treatment. To further validate the functional relevance, we introduced zonula occludens-1 (ZO-1), a representative tight junction protein, as a functional verification indicator. Our results demonstrated that G. parasuis infection significantly downregulated the expression of both ZO-1 and β-catenin in human brain microvascular endothelial cells (hBMECs), while berberine (2.5, 10, and 20 μg/mL) treatment effectively reversed this downregulation in a concentration-dependent manner. These findings reveal that berberine exerts its protective effects against G. parasuis meningitis by targeting CTNNB1 to restore intercellular junctional integrity-including tight junctions (ZO-1) and adherens junctions (β-catenin)-thereby preserving BBB function. This study provides a mechanistic basis for the development of berberine as a promising alternative therapeutic agent against G. parasuis meningitis.
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BibTeX
@article{guo2026berberine,
title = {{Berberine Protects Brain Endothelial Barrier via β-Catenin: A Network Pharmacology in Pigs and In Vitro Mechanistic Analysis.}},
author = {Pu Guo and Yangfan Dong and Yu Cheng and Yunda Xue and Qirong Lu and Zhongyuan Wu and Chun Ye and Yu Liu and Yinsheng Qiu},
journal = {Animals : an open access journal from MDPI},
year = {2026},
month = oct,
doi = {10.3390/ani16203240},
url = {https://europepmc.org/article/MED/42939171},
note = {CC BY},
}
RIS
TY - JOUR
TI - Berberine Protects Brain Endothelial Barrier via β-Catenin: A Network Pharmacology in Pigs and In Vitro Mechanistic Analysis.
AU - Pu Guo
AU - Yangfan Dong
AU - Yu Cheng
AU - Yunda Xue
AU - Qirong Lu
AU - Zhongyuan Wu
AU - Chun Ye
AU - Yu Liu
AU - Yinsheng Qiu
PY - 2026
DA - 2026/10/15
JO - Animals : an open access journal from MDPI
DO - 10.3390/ani16203240
UR - https://europepmc.org/article/MED/42939171
AB - Glaesserella parasuis (G. parasuis) is an important swine pathogen that causes Glässer's disease, of which meningitis is among the most severe clinical symptoms. However, the molecular mechanisms underlying G. parasuis-induced meningitis remain poorly understood. In this study, we employed a network pharmacology-based strategy combined with in vitro experimental validation to investigate the protective effects and mechanisms of berberine against G. parasuis meningitis. Network pharmacology analysis identified CTNNB1 (encodes the β-catenin protein) as a core target among multiple candidate targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the predicted targets of berberine are significantly associated with inflammatory signaling (mitogen-activated protein kinase MAPK/nuclear factor kappa B NF-κB) and stress-response pathways (forkhead box O FoxO/p53), suggesting a multifaceted protective mechanism against G. parasuis-induced blood-brain barrier (BBB) disruption. Molecular docking results combined with drug affinity responsive target stability (DARTS) assays demonstrated that berberine binds directly to β-catenin with high affinity (docking score = -7.52 kcal/mol), as evidenced by enhanced proteolytic stability of β-catenin upon berberine (2.5, 10, and 20 μg/mL) treatment. To further validate the functional relevance, we introduced zonula occludens-1 (ZO-1), a representative tight junction protein, as a functional verification indicator. Our results demonstrated that G. parasuis infection significantly downregulated the expression of both ZO-1 and β-catenin in human brain microvascular endothelial cells (hBMECs), while berberine (2.5, 10, and 20 μg/mL) treatment effectively reversed this downregulation in a concentration-dependent manner. These findings reveal that berberine exerts its protective effects against G. parasuis meningitis by targeting CTNNB1 to restore intercellular junctional integrity-including tight junctions (ZO-1) and adherens junctions (β-catenin)-thereby preserving BBB function. This study provides a mechanistic basis for the development of berberine as a promising alternative therapeutic agent against G. parasuis meningitis.
SN - 2076-2615
ER -