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https://hdl.handle.net/20.500.14365/6237
Title: | 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 | Authors: | Baris, Elif Portakal, Huseyin Saygin Aslan, Arda Karagonlar, Zeynep Firtina Tosun, Metiner |
Keywords: | Liraglutide Prostaglandins Inflammation Cyclooxygenase Cholinergic Nicotinic In Silico Analysis |
Publisher: | Springer | 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 the anti-inflammatory effects of liraglutide in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. Results demonstrate that increasing concentrations of liraglutide suppresses LPS-elevated prostaglandin E2 (PGE2), 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha, a stable prostacyclin metabolite) and thromboxane A2 (TXA2), similar to that observed with conventional anti-inflammatory agents, ibuprofen and celecoxib. Mechanistic exploration reveals that liraglutide's anti-inflammatory action is dually-modulated by cyclooxygenase (COX) and nicotinic acetylcholine receptor (nAChR) signaling. The application of non-selective, non-competitive nAChR antagonist or selective and potent alpha 7-nAChR antagonist, mecamylamine (MEC) and methyllycaconitine (MLA), respectively, highlights the involvement of cholinergic pathways in liraglutide's activity. Based on in silico molecular docking analyses, liraglutide exhibits favorable binding affinities to COX-1, COX-2, prostacyclin synthase (PGIS), and alpha 7nAChRs, supporting its potential multi-target anti-inflammatory effects. These findings suggest that the therapeutic potential of liraglutide may go beyond metabolic regulation and may be promising for conditions in which metabolic and inflammatory pathways converge, including inflammation and modulation of cholinergic signaling. | URI: | https://doi.org/10.1007/s00210-025-04225-5 https://hdl.handle.net/20.500.14365/6237 |
ISSN: | 0028-1298 1432-1912 |
Appears in Collections: | PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection |
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