Silu Hou, Danyang Ma, Shaofeng Wu, Yarong Gong, Xiaosong Zhang, Zhihui Hao
Current study evaluated the clinical efficacy of a compound berberine sulfate injection (CBSI) as an antibiotic-sparing strategy and explored its underlying mechanisms against Enteropathogenic and Enterotoxigenic Escherichia coli (ETEC/EPEC) induced diarrhea in weaned piglets. A total of 180 diarrheic piglets were randomly assigned to six groups (n = 30): Berberine (BBR) group, Colistin Sulfate (CS) group, three CBSI groups (CBL, CBM, CBH at 0.05, 0.1, and 0.2 mL/kg, respectively), and a non-treated control (CON) group. Treatments were administered intramuscularly for 3 consecutive days. CBSI at 0.1 mL/kg, containing a 50% reduced dose of colistin, achieved a clinical cure rate of 83.18% ± 7.28%, comparable to full-dose colitin (82.71% ± 6.92%) and higher than BBR alone (53.74% ± 7.28%), with no significant differences among groups (p > 0.05). Pathogen clearance rates reached 80.95% for ETEC and 90.15% for EPEC in the CBSI group, indicating effective bacterial control. In addition, CBSI improved feed conversion efficiency compared with the untreated control group. Mechanistically, network pharmacology identified 73 intersecting targets, with KEGG enrichment suggesting involvement of inflammatory signaling pathways, including TNF and IL-17. Molecular docking, supported by successful native-ligand redocking for PTGS2 and MAPK14, suggested potential interactions between berberine and selected inflammatory targets; however, these findings remain predictive. These findings suggest that CBSI at 0.1 mL/kg may serve as an effective antibiotic-sparing strategy that maintains therapeutic efficacy while reducing colistin dosage by 50%.