Samur, Dilara Nemutlu2026-01-242026-01-2420250014-29991879-0712https://doi.org/10.1016/j.ejphar.2025.177932https://hdl.handle.net/20.500.12868/5678Neuroinflammation is a key contributor to neurodegenerative diseases, including Parkinson's disease (PD). Nonmotor symptoms such as gut-derived inflammation often precede motor deficits and represent an early stage of PD pathology. We aimed to investigate the anti-inflammatory potential of losartan and captopril on rotenoneinduced inflammation in enteric glial cells (EGCs), focusing on the modulation of the TLR4/NLRP3 inflammasome signaling pathway. EGCs were treated with rotenone (1 mu M) to induce inflammation. Non-cytotoxic drug concentrations (10-100 mu M) were identified by cell viability assays. Caspase-1 and IL-1beta levels were quantified via ELISA, and mRNA expression of TLR4/NLRP3 was assessed by RT-qPCR. Molecular docking was performed to predict drug interactions with TLR4 and NLRP3 proteins. Rotenone significantly increased caspase-1 levels and TLR4/NLRP3 expression. Losartan at 10 mu M significantly reduced rotenone-induced NLRP3 mRNA expression, while captopril required a higher concentration (100 mu M) for a comparable inhibitory effect. Paradoxically, losartan and captopril alone increased caspase-1 and/or TLR4 expression, suggesting dose-dependent pro-inflammatory effects. Molecular docking showed a stronger binding affinity for losartan compared to captopril toward TLR4/NLRP3 proteins, consistent with observed biochemical effects. Our results highlight the therapeutic potential of losartan and captopril as modulators of TLR4/NLRP3-mediated inflammation.eninfo:eu-repo/semantics/openAccessParkinson's diseaseInflammationTLR4NLRP3LosartanCaptoprilRotenoneArticle10.1016/j.ejphar.2025.1779321003406455492-s2.0-105010183195Q1WOS:001539077300001Q1