Combination of Empagliflozin With Curcumin Attenuates Hepatic Inflammation in High-Fat Diet-Fed Mice Via Macrophage Polarization Remodeling and Nf-Κb Modulation Publisher



Aliabadi M ; Soleimani A A ; Taheripak G ; Nourbakhsh M ; Meshkani R
Source: Journal of Diabetes and Metabolic Disorders Published:2026

Abstract

Purpose: To evaluate the combined effects of empagliflozin (EMPA) and curcumin (Cur) on hepatic macrophage polarization, cytokine profile, and NF-κB signaling in a mouse model of metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: Male C57BL/6J mice (n = 10/group) were fed NCD, HFD, HFD+EMPA, HFD + Cur, or HFD+EMPA + Cur for 23 weeks. Hepatic macrophage infiltration (F4/80 immunofluorescence), M1/M2 polarization markers (CD11c, CD206, Arg-1), cytokine levels (TNF-α, IL-6, IL-1β, IL-10), NF-κB p65 expression (Western blot), and histopathology (H&E) were assessed. Results: HFD induced macrophage infiltration, predominant M1 polarization, increased pro-inflammatory cytokine levels, and upregulation of NF-κB p65. Both EMPA and Cur monotherapies partially attenuated these changes. Co-administration produced the most pronounced effects: significantly reducing macrophage infiltration (p < 0.001), suppressing CD11c (p < 0.001), restoring CD206 and Arg-1 (p < 0.01 for both), markedly reducing TNF-α, IL-6, and IL-1β (p < 0.001 for all), elevating IL-10 (p < 0.001), and suppressing total NF-κB p65 protein expression (p < 0.001). Conclusion: Co-administration of EMPA and Cur attenuates HFD-induced hepatic inflammation by remodeling macrophage polarization from M1 toward the M2 phenotype and attenuating NF-κB-associated inflammatory signaling, as reflected by reduced total p65 protein expression, with effects more pronounced than either agent alone. © The Author(s), under exclusive licence to Tehran University of Medical Sciences 2026.