Carbamazepine

In female non‑obese diabetic (NOD) mice, dietary carbamazepine (0.5% w/w) achieved serum levels of ~15 µM and reduced diabetes incidence by approximately 50% over 25 weeks. Carbamazepine‑treated mice showed improved glucose tolerance at 6 weeks of age, before diabetes onset, and exhibited less insulitis. No significant changes were observed in CD4⁺/CD8⁺ T cell composition in pancreatic lymph nodes or circulating inflammatory markers. The findings indicate that the sodium channel blocker carbamazepine protects against autoimmune diabetes by maintaining functional beta‑cell mass rather than broadly altering systemic immunity.

Fig. 1 Oral carbamazepine ameliorates diabetes incidence NOD mice. (Lee JTC, et al., 2018)

In cultured macrophages and a murine model of Clostridioides difficile infection (CDI), the exotoxin TcdB inhibited CTNNB1/β‑catenin activity, downregulated MITF, and reduced expression of vacuolar ATPase components, leading to lysosome acidification failure. This impaired autophagic flux and activated SQSTM1‑NFκB signaling, driving pro‑inflammatory cytokines. Vitamin D₃ and carbamazepine restored MITF expression and lysosomal acidification, reducing inflammation and tissue damage. These findings identify the CTNNB1‑MITF‑lysosome axis as a therapeutic target in CDI and support repurposing of vitamin D₃ or carbamazepine as adjunctive treatments.

Fig. 2 Effects of lysosome activators 1α,25-dihydroxyvitamin D3 and carbamazepine on TcdB-induced autophagic flux impairment and cytokine response in human PMA-differentiated THP-1 macrophages. (Chan H, et al., 2022)