ABSTRACT
Research interest in examining Elaeagnus angustifolia's potential as a source of anti-inflammatory and antioxidant agents has grown as a result of the plant's endorsement as a rich source of bioactive chemicals with promising anti-inflammatory and antioxidant activity. In this study, zinc oxide (Fe0.25-ZnO) bimetallic nanoparticles (E.ang-Fe0.25-ZnO NPs) were synthesized using an aqueous extract of Elaeagnus angustifolia. Synthesized Fe0.25-ZnO nanoparticles were characterized by FTIR and XRD. The anti-inflammatory and antioxidant activities were investigated in LPS-stimulated RAW 264.7 macrophages using RT-PCR and ELISA techniques for antioxidant- and inflammation-related genes. The concentration of 39.6â µg/ml of E.ang-Fe0.25-ZnO NPs demonstrated a significant anti-inflammatory activity by suppressing the mRNA levels of TNF-α and IL-6 by 88.3 %±1.9 and 93.6 %±0.1, respectively, compared to LPS-stimulated cells. This was confirmed by the significant reduction of TNF-α and IL-6 secretion levels from 95.2 and 495.6â pg/ml in LPS-stimulated cells to 5.6 and 26.5â pg/ml in E.ang-Fe0.25-ZnO treated group. In addition, E.ang-Fe0.25-ZnO NPs nanoparticles treatment significantly enhanced the expression of antioxidant-related genes, SOD and CAT. Together, our results proved that phyto-mediated Fe0.25-ZnO nanoparticles using Elaeagnus angustifolia have great potential in biomedical applications such as anti-inflammatory and antioxidant.
ABSTRACT
The nuclear receptor-related factor 1 (Nurr1), an orphan nuclear receptor in microglia, has been recognized as a major player in attenuating the transcription of the pro-inflammatory genes to maintain CNS homeostasis. In this study, we investigate Nurr1 trans-repression activity by targeting this receptor with one of the indole derivatives 3-Indole acetic acid hydrazide (IAAH) loaded onto zinc iron oxide (ZnFe2O4) NPs coated with PEG. XRD, SEM, FTIR, UV-Vis spectroscopy, and DLS were used to characterize the synthesized IAAH-NPs. The anti-inflammatory properties of IAAH-NPs on LPS-stimulated SimA9 microglia were assayed by measuring pro-inflammatory cytokine gene expressions and protein levels using RT-PCR and ELISA, respectively. As a result, IAAH-NPs showed an ability to suppress pro-inflammatory genes, including IL-6, IL-1ß, and TNF-α in LPS-stimulated SimA9 via targeting Nurr1. The current study suggests that ZnFe2O4 NPs as a delivery system can increase the efficiency of cellular uptake and enhance the IAAH ability to inhibit the pro-inflammatory cytokines. Collectively, we demonstrate that IAAH-NPs is a potential modulator of Nurr1 that combines nanotechnology as a delivery system to suppress neuroinflammation in CNS which opens a window for possible ambitious neuroprotective therapeutic approaches to neuro disorders.