Omarigliptin

Alsufyani SE, et al. Life Sciences, 2025, 376, 123758.

This study investigated the protective effects of omarigliptin against cisplatin-induced nephrotoxicity using forty Wistar rats randomized into four groups: control, cisplatin-only, and cisplatin combined with omarigliptin at 2.5 or 5 mg/kg/day. Cisplatin was administered intraperitoneally at escalating weekly doses (0.8-4.8 mg/kg). Omarigliptin was delivered orally starting one week before cisplatin exposure and continued for six days post-final cisplatin injection. Renal function, oxidative stress markers, inflammatory mediators, autophagy activity, and morphological alterations were assessed. Results demonstrated that omarigliptin dose-dependently enhanced GLP-1 signaling, restored redox balance, attenuated pyroptosis via TXNIP/NLRP3/gasdermin D axis, and mitigated histopathological damage. This experimental approach highlights omarigliptin's potential as a renoprotective agent during platinum-based chemotherapy.

MA Abd Elmaaboud, et al. Biomedicine & Pharmacotherapy, 2024, 177, 117026.

In a preclinical study, the protective effects of omarigliptin, alone or in combination with rosinidin, were evaluated against cyclophosphamide-induced pulmonary toxicity in rats. Experimental groups received cyclophosphamide to induce lung injury, followed by oral administration of omarigliptin (with or without rosinidin). Lung tissues were analyzed biochemically for antioxidant enzyme activity, inflammatory cytokines, and glucagon-like peptide-1 levels. Histopathological assessment examined fibrosis, apoptosis, and autophagy markers. Molecular investigations included HMGB1/RAGE/NF-κB axis modulation and TXNIP/NLRP3 inflammasome signaling. Omarigliptin/rosinidin co-treatment synergistically restored redox balance, mitigated inflammation, regulated autophagy/apoptosis, and reduced fibrogenic responses, demonstrating a robust experimental application of omarigliptin in attenuating chemotherapeutic lung injury.

Kabel AM, et al. Life Sciences, 2022, 295, 120396.

This study investigated the therapeutic potential of omarigliptin alone and in combination with galangin against lipopolysaccharide (LPS)-induced neuroinflammation in rats. Behavioral assessments, including cognitive and motor function tests, were conducted to evaluate neurological performance. Biochemical analyses measured oxidative stress markers, toll-like receptor-4 (TLR-4) levels, glucagon-like peptide-1 (GLP-1) expression, and apoptotic indicators in cerebral tissues. Western blotting quantified phospho-Akt, GSK-3β, and autophagy-related protein beclin-1, while histopathological and electron microscopic examinations assessed neuronal integrity. Omarigliptin administration restored antioxidant defenses, suppressed TLR-4-mediated inflammation, modulated Akt/GSK-3β signaling, and enhanced autophagy. Notably, the combination with galangin produced superior neuroprotective effects, demonstrating the experimental applicability of omarigliptin in mitigating LPS-triggered neuroinflammatory pathways.

Ma L, et al. Molecular Immunology, 2022, 141, 108-115.

This study investigated the protective effects of Omarigliptin against lipopolysaccharide (LPS)-induced injury in BEAS-2B human bronchial epithelial cells. Cells were pretreated with Omarigliptin prior to LPS exposure, and oxidative stress was assessed by measuring mitochondrial reactive oxygen species (ROS) and reduced glutathione (GSH) levels. Inflammatory responses were quantified via ELISA for IL-1β, IL-12, and MCP-1. MUC5AC overproduction was evaluated using immunoblotting, while SOCS1 expression was determined to elucidate signaling mechanisms. Mechanistic studies indicated that Omarigliptin's modulation of SOCS1 was mediated through AMPK activation. Experimental results demonstrated that Omarigliptin significantly reduced ROS, restored GSH, suppressed pro-inflammatory cytokines, and mitigated MUC5AC overproduction, highlighting its potential as a therapeutic agent for chronic inflammatory lung diseases.