Investigation of the effects of losartan and captopril on rotenone-induced inflammation via TLR4/NLRP3 pathway: An integrative in vitro and in silico study

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dc.contributor.authorSamur, Dilara Nemutlu
dc.date.accessioned2026-01-24T12:31:08Z
dc.date.available2026-01-24T12:31:08Z
dc.date.issued2025
dc.departmentAlanya Alaaddin Keykubat Üniversitesi
dc.description.abstractNeuroinflammation 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.
dc.identifier.doi10.1016/j.ejphar.2025.177932
dc.identifier.issn0014-2999
dc.identifier.issn1879-0712
dc.identifier.pmid40645549
dc.identifier.scopus2-s2.0-105010183195
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.ejphar.2025.177932
dc.identifier.urihttps://hdl.handle.net/20.500.12868/5678
dc.identifier.volume1003
dc.identifier.wosWOS:001539077300001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofEuropean Journal of Pharmacology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WoS_20260121
dc.subjectParkinson's disease
dc.subjectInflammation
dc.subjectTLR4
dc.subjectNLRP3
dc.subjectLosartan
dc.subjectCaptopril
dc.subjectRotenone
dc.titleInvestigation of the effects of losartan and captopril on rotenone-induced inflammation via TLR4/NLRP3 pathway: An integrative in vitro and in silico study
dc.typeArticle

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