{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:29:39Z","timestamp":1792096179576,"version":"4.4.0"},"reference-count":52,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T00:00:00Z","timestamp":1739577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Research and Development Plan of Hubei Province, China","award":["2023BBB069"],"award-info":[{"award-number":["2023BBB069"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>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\u2013protein 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\u2013brain barrier. The molecular docking results indicated key binding activity between TLR4\u2013berberine and FN1\u2013berberine. 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.<\/jats:p>","DOI":"10.3390\/toxics13020138","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T03:41:47Z","timestamp":1739763707000},"page":"138","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Network Pharmacology to Unveil the Mechanism of Berberine in the Treatment of Streptococcus suis Meningitis in Humans and Pigs"],"prefix":"10.3390","volume":"13","author":[{"given":"Pu","family":"Guo","sequence":"first","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China"},{"name":"Wuhan Engineering and Technology Research Center of Animal Disease-Resistant Nutrition, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunda","family":"Xue","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China"},{"name":"Wuhan Engineering and Technology Research Center of Animal Disease-Resistant Nutrition, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China"},{"name":"Wuhan Engineering and Technology Research Center of Animal Disease-Resistant Nutrition, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qirong","family":"Lu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China"},{"name":"Wuhan Engineering and Technology Research Center of Animal Disease-Resistant Nutrition, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, 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430023, China"},{"name":"Wuhan Engineering and Technology Research Center of Animal Disease-Resistant Nutrition, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulin","family":"Fu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China"},{"name":"Wuhan Engineering and Technology Research Center of Animal Disease-Resistant Nutrition, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China"},{"name":"Wuhan Engineering and Technology Research Center of Animal Disease-Resistant Nutrition, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6476-0509","authenticated-orcid":false,"given":"Xu","family":"Wang","sequence":"additional","affiliation":[{"name":"National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinsheng","family":"Qiu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China"},{"name":"Wuhan Engineering and Technology Research Center of Animal Disease-Resistant Nutrition, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Liedel, C., Rieckmann, K., and Baums, C.G. 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