The Nurr1 ligand indole acetic acid hydrazide loaded onto ZnFe2O4 nanoparticles suppresses proinflammatory gene expressions in SimA9 microglial cells

• Published in: Scientific reports 2024-06, Vol.14 (1), p.13987-11, Article 13987
• Main Authors: Qasim, Raneen, Thiab, Tuqa Abu, Alhindi, Tareq, Al-Hunaiti, Afnan, Imraish, Amer
• Format: Article
• Language: English
• Subjects: 3-Indole acetic acid hydrazide; 631/250; 631/337; 631/378; 631/80; Acetic acid; Animals; Anti-inflammatory; Anti-inflammatory agents; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Cell Line; Cytokines - metabolism; Enzyme-linked immunosorbent assay; Ferric Compounds - chemistry; Ferric Compounds - pharmacology; Gene Expression Regulation - drug effects; Genes; Homeostasis; Humanities and Social Sciences; Indoleacetic acid; Indoleacetic Acids; Indoles; Indoles - chemistry; Indoles - pharmacology; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Iron oxides; Ligands; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Mice; Microglia; Microglia - drug effects; Microglia - metabolism; multidisciplinary; Nanoparticles; Nanoparticles - chemistry; Nanotechnology; Neuroprotection; Nuclear Receptor Subfamily 4, Group A, Member 2 - genetics; Nuclear Receptor Subfamily 4, Group A, Member 2 - metabolism; Nuclear receptors; Nurr1; Nurr1 protein; Polyethylene glycol; Science; Science (multidisciplinary); Tumor necrosis factor-α
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-64820-z

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 (ZnFe 2 O 4 ) 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-1β, and TNF-α in LPS-stimulated SimA9 via targeting Nurr1. The current study suggests that ZnFe 2 O 4 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.