{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:25:27Z","timestamp":1787030727880,"version":"build-2736575974"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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-\u03baB, IL-6, and TNF-\u03b1 were evaluated by qRT-PCR, Western blotting, immunofluorescence, and ELISA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Bioinformatic enrichment highlighted AGE-RAGE signaling and inflammation-related NF-\u03baB 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-\u03baB phosphorylation and immunofluorescence-based nuclear accumulation, and lower IL-6 and TNF-\u03b1 expression and secretion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Empagliflozin attenuates AGE-BSA\/high-glucose-induced inflammatory injury in C2C12 myotubes, and this effect is associated with reduced activation of RAGE\/NF-\u03baB-related inflammatory signaling. Further gain- or loss-of-function experiments and validation in diabetic animal models are required to determine whether this pathway is causally involved and whether the observed cell-based effect can be translated into an in vivo setting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1903580","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:28:58Z","timestamp":1787027338000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Empagliflozin attenuates AGE-BSA\/high-glucose-induced inflammation in C2C12 myotubes associated with suppression of the RAGE\/NF-\u03baB pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaoying","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Zhengzhou Central Hospital Affiliated to Zhengzhou University","place":["Zhengzhou, Henan, 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