Molecular Neurobiology, 2024 (SCI-Expanded)
Studies in the existing literature propose that allocryptopine possesses both antioxidant and anti-inflammatory properties, showcasing its neuroprotective effects by potentially mitigating oxidative stress and inflammation. This study aims to investigate the antioxidant and anti-inflammatory effects of allocryptopine on various targets and potential mechanisms that have not been previously explored in the literature. Initially, we used MTT and LDH methods to evaluate the effects of allocryptopine on cell viability in BV-2 cells exposed to LPS-induced damage. Subsequently, we evaluated the impact of allocryptopine on pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), other inflammatory mediators (Cox-2 and iNOS), and p38 MAPK genes and proteins through qRT-PCR and Western blot analyses. Also, we evaluated the impact of allocryptopine on NF-κB proteins (TLR4, MyD88, IκBα, p-p50, and p-p65) through ELISA assay. Molecular docking analyses were performed to investigate the potential binding of allocryptopine to target proteins (TLR4, MyD88, IκBα, p50, p65, MKK3, MKK4, MKK6, p38, AP-1 (c-Jun and ATF2), IL-1β, IL-6, TNF-α, Cox-2, and iNOS) associated with the TLR4, NF-κB, and p38 MAPK pathways. Our results indicate that allocryptopine exerts a comprehensive influence on pro-inflammatory cytokines and other inflammatory mediators by inhibiting TLR4 signaling and modulating the NF-κB and p38 MAPK pathways. The outcomes of our study suggest that the antioxidant and anti-inflammatory efficacy of allocryptopine is intricately linked to the modulation of key molecular pathways associated with oxidative stress and inflammation. These findings highlight the potential of allocryptopine as a therapeutic agent for addressing neurodegenerative diseases by safeguarding neuronal health. Graphical Abstract: (Figure presented.)