Nobiletin and Eriodictyol Suppress Release of IL-1β, CXCL8, IL-6, and MMP-9 from LPS, SARS-CoV-2 Spike Protein, and Ochratoxin A-Stimulated Human Microglia

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 636 - 636

Published: Jan. 14, 2025

Neuroinflammation is involved in various neurological and neurodegenerative disorders which the activation of microglia one key factors. In this study, we examined anti-inflammatory effects flavonoids nobiletin (5,6,7,8,3′,4′-hexamethoxyflavone) eriodictyol (3′,4′,5,7-tetraxydroxyflavanone) on human cell line stimulated by either lipopolysaccharide (LPS), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) full-length Spike protein (FL-Spike), or mycotoxin ochratoxin A (OTA). Human were preincubated with (10, 50, 100 µM) for h, following which, they 24 h. The inflammatory mediators interleukin-1 beta (IL-1β), chemokine (C-X-C motif) ligand 8 (CXCL8), IL-6, matrix metalloproteinase-9 (MMP-9) quantified culture supernatant enzyme-linked immunosorbent assay (ELISA). Both significantly inhibited LPS, FL-Spike, OTA-stimulated release IL-1β, CXCL8, MMP-9 at 50 µM, while, most cases, was also effective 10 pronounced reductions µM. These findings suggest that both are potent inhibitors pathogen-stimulated microglial mediators, highlighting their potential therapeutic application neuroinflammatory diseases, such as long COVID.

Language: Английский

Repetitive Low-Level Blast Exposure Alters Circulating Myeloperoxidase, Matrix Metalloproteinases, and Neurovascular Endothelial Molecules in Experienced Military Breachers

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1808 - 1808

Published: Feb. 20, 2025

Repeated exposure to low-level blast overpressure, frequently experienced during explosive breaching and heavy weapons use in training operations, is increasingly recognised as a serious risk the neurological health of military personnel. Although research on underlying pathobiological mechanisms humans remains limited, this study investigated effects such circulating molecular biomarkers associated with inflammation, neurovascular damage, endothelial injury. Blood samples from breachers were analysed for myeloperoxidase (MPO), matrix metalloproteinases (MMPs), junctional proteins indicative blood-brain barrier (BBB) disruption including occludin (OCLN), zonula occludens-1 (ZO-1), aquaporin-4 (AQP4), syndecan-1 (SD-1). The results revealed significantly elevated levels MPO, MMP-3, MMP-9, MMP-10 compared unexposed controls, suggesting heightened oxidative stress, vascular Increased OCLN SD-1 further indicated BBB glycocalyx degradation breachers. These findings highlight potential chronic unit damage/dysfunction repeated underscore importance early targeted interventions-such reducing reinforcing integrity, managing inflammation-that could be essential mitigating long-term impairment exposure.

Language: Английский

Tenascin-C Facilitates Microglial Polarization via TLR4/MyD88/NF-κB Pathway Following Subarachnoid Hemorrhage

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 3555 - 3570

Published: March 1, 2025

Purpose: This study primarily aims to elucidate the underlying mechanism of Tenascin-C in neuroinflammation and microglia polarization a mouse model subarachnoid hemorrhage (SAH). Methods: The was constructed by injecting blood into anterior chiasmatic cistern stimulating primary with hemoglobin vitro. Then, Imatinib mesylate used inhibit Tenascin-C. Through neurological function scoring, brain edema, cell extraction, immunofluorescence staining, CCK8, Tunel Elisa, Western blot other methods, potential induced explored. Results: results this observed that expression up-regulated after hemorrhage. Inhibiting increase imatinib could significantly ameliorate neuroinflammation, neuronal apoptosis, barrier disruption edema. When level decreased, numbers TLR4 positive, MyD88 positive NF-κB microglial cells decreased accordingly. Moreover, hemorrhage, number for M1-type markers increased significantly. After inhibited Tenascin-C, M2-type Conclusion: In summary, elevated induces activation microglia, releasing large inflammatory factors aggravating early injury. Keywords: SAH,

Language: Английский