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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Tarih
2025
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Neuroinflammation 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.
Açıklama
Anahtar Kelimeler
Parkinson's disease, Inflammation, TLR4, NLRP3, Losartan, Captopril, Rotenone
Kaynak
European Journal of Pharmacology
WoS Q Değeri
Q1
Scopus Q Değeri
Q1
Cilt
1003
