Liraglutide modulates cyclooxygenase and α7 acetylcholine receptors: in vitro and in silico insights into its anti-inflammatory role in LPS-induced inflammation in RAW 264.7 macrophages

• DOI: 10.1007/s00210-025-04225-5
• Publication Date: 2025-05-31T10:02:39Z
• Authors: Elif Baris; Huseyin Saygin Po...; Arda Aslan; Zeynep Firtina Ka...; Metiner Tosun
• Keywords: Methyllycaconitine

Abstract Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is well-established for its metabolic benefits, including glycemic control and weight loss. Beyond these roles, it exhibits significant anti-inflammatory properties, though the mechanisms remain underexplored. This study investigates effects of liraglutide in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. Results demonstrate that increasing concentrations suppresses LPS-elevated prostaglandin E2 (PGE2), 6-keto F1α (6-keto-PGF 1α , stable prostacyclin metabolite) thromboxane A2 (TXA2), similar to observed with conventional agents, ibuprofen celecoxib. Mechanistic exploration reveals liraglutide's action dually-modulated by cyclooxygenase (COX) nicotinic acetylcholine (nAChR) signaling. The application non-selective, non-competitive nAChR antagonist or selective potent α7-nAChR antagonist, mecamylamine (MEC) methyllycaconitine (MLA), respectively, highlights involvement cholinergic pathways activity. Based on silico molecular docking analyses, favorable binding affinities COX-1, COX-2, synthase (PGIS), α7nAChRs, supporting potential multi-target effects. These findings suggest therapeutic may go beyond regulation be promising conditions which inflammatory converge, inflammation modulation