Empagliflozin attenuates AGE-BSA/high-glucose-induced inflammation in C2C12 myotubes associated with suppression of the RAGE/NF-κB pathway
Abstract
Introduction: Empagliflozin is an established sodium-glucose cotransporter 2 inhibitor with reported anti-inflammatory activity, but its effects on advanced glycation end product/high-glucose-induced inflammatory injury in skeletal muscle cells remain unclear.
Methods: A GEO-derived transcriptomic dataset from gastrocnemius muscle of type 2 diabetes mellitus rats was analyzed to screen pathways associated with diabetes-related skeletal muscle injury, and molecular docking was performed to explore the possible structural compatibility between empagliflozin and RAGE. Differentiated C2C12 myotubes were exposed to AGE-BSA under high-glucose conditions and treated with empagliflozin. Cell viability was assessed using CCK-8, and RAGE, NF-κB, IL-6, and TNF-α were evaluated by qRT-PCR, Western blotting, immunofluorescence, and ELISA.
Results: Bioinformatic enrichment highlighted AGE-RAGE signaling and inflammation-related NF-κB pathways in diabetic skeletal muscle. Molecular docking provided a computational structural hypothesis suggesting possible compatibility between empagliflozin and human RAGE involving Asp160. In AGE-BSA/high-glucose-stimulated C2C12 myotubes, empagliflozin improved cell viability and was accompanied by reduced RAGE expression, lower NF-κB phosphorylation and immunofluorescence-based nuclear accumulation, and lower IL-6 and TNF-α expression and secretion.
Discussion: Empagliflozin attenuates AGE-BSA/high-glucose-induced inflammatory injury in C2C12 myotubes,…
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