Combined acylated catalpol diglycoside and Lactobacillus therapy restores the miR-146a-TRAF6-SIRT1/AMPK signaling axis in experimental colitis.

PMID 42155683 | DOI 10.1016/j.taap.2026.117874 · Toxicology and applied pharmacology · 2026

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Inflammatory bowel disease is characterized by altered innate immunity, oxidative stress, and gut microbiota imbalance. This study explored the association between miR-146a expression and the TRAF6-NF-κB-SIRT1-AMPK axis and assessed the therapeutic potential of an acylated catalpol diglycoside (CAT) and a Lactobacillus preparation containing Lactobacillus delbrueckii and Lactobacillus fermentum (LB) in dextran sodium sulfate (DSS)-induced colitis. Colonic injury, oxidative stress, inflammatory mediators, selected gut microbial markers, and molecular signaling were evaluated using histopathology, immunohistochemistry, ELISA, qPCR, and Western blotting. DSS induced marked colonic damage, inflammatory cytokine elevation, oxidative stress, alterations in selected gut microbial taxa, NF-κB activation, SIRT1/AMPK suppression, and miR-146a downregulation. CAT or LB alone partially improved inflammatory and oxidative stress parameters, although changes in miR-146a, SIRT1, and AMPK activation did not reach statistical significance. In contrast, combined CAT+LB treatment was associated with the greatest recovery of miR-146a expression, SIRT1 levels, AMPK activation, and overall colonic protection. Correlation, regression, and mediation analyses supported an inferred upstream network-associated position for miR-146a in relation to TRAF6-NF-κB activity and SIRT1/AMPK signaling. DSS-normalized synergy modeling indicated non-additive network-level effects on miR-146a restoration, TRAF6 suppression, NF-κB attenuation, and SIRT1/AMPK recovery. Collectively, these findings support miR-146a as a putative network-associated regulatory node and suggest that CAT+LB promotes coordinated immune-metabolic recovery in acute DSS-induced colitis.