In-Vitro Evaluation of the Anti-Inflammatory Potential of Empagliflozin Via Nf-Κb Pathway Inhibition
Abstract
Background: Empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, exhibits profound cardioprotective and renoprotective benefits that extend beyond its primary role in glycemic control. Emerging evidence suggests these pleiotropic effects are driven by intrinsic immune-modulating properties. This study aimed to systematically evaluate the in vitro anti-inflammatory efficacy and the underlying molecular mechanisms of empagliflozin in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods: Macrophages were pre-treated with safe, non-cytotoxic concentrations of empagliflozin (10, 25, and 50 μM), determined via CCK-8 assay, prior to stimulation with LPS (1 μg/mL). Extracellular nitric oxide (NO) production was quantified using the Griess reagent, and the secretion of primary pro-inflammatory cytokines (TNFα, IL-6, and IL-1β) was measured via highly sensitive enzyme-linked immunosorbent assays (ELISA). Compartmentalized protein extraction and Western blotting were executed to evaluate the modulation of the nuclear factor-kappa B (NF-κB) signaling axis. Results: Empagliflozin maintained macrophage viability (>96%) at all tested doses. Upon LPS stimulation, empagliflozin dose-dependently and significantly (p < 0.001) attenuated the hyper-secretion of NO, TNF-α, IL-6, and IL-1β. Mechanistic evaluations revealed that empagliflozin robustly rescued cytosolic IκBα from degradation and simultaneously suppressed the phosphorylation of the p65 subunit (p-p65).…
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