Combination of empagliflozin with curcumin attenuates hepatic inflammation in high-fat diet-fed mice via macrophage polarization remodeling and NF-κB modulation
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 p p p p 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.
Supplementary information: The online version contains supplementary material available at 10.1007/s40200-026-02013-3.
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