Poncirin ameliorates oxygen glucose deprivation/reperfusion injury in cortical neurons via inhibiting NOX4-mediated NLRP3 inflammasome activation.

Abstract

Poncirin, a natural flavonoid present abundantly in citrus fruits, possesses anti-oxidant and anti-inflammatory activities that contribute to neuroprotection, but its roles and mechanisms in neuronal injury is still poorly understood. In this study, an oxygen-glucose deprivation/reoxygenation (OGD/R) model was established in primary cortical neurons to induce neuronal injury in vitro. Poncirin effectively attenuated OGD/R-induced neuronal damage by enhancing cell viability, restraining lactate dehydrogenase release, and reducing apoptosis of neurons. Poncirin restrained mitochondrial dysfunction and oxidative stress by increasing mitochondrial membrane potential, declining reactive oxygen species production, lessening malondialdehyde generation, and increasing the activities of antioxidant enzymes in OGD/R-treated neurons. Poncirin also repressed inflammatory responses by reducing the secretion of pro-inflammatory factors, and inhibiting NLRP3 inflammasome activation. Importantly, poncirin administration notably abolished OGD/R-induced upregulation of NADPH oxidase 4 (NOX4), and overexpression of NOX4 neutralized poncirin-mediated neuroprotection. In conclusion, poncirin protects cortical neurons from OGD/R injury via inhibiting NOX4/ROS/NLRP3 axis.

• Authors: Ruili Wang, Lei Li, Baogong Wang
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 102 Pg. 107210 (Jan 2022) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 34266770 (Publication Type: Journal Article)
• Copyright: Copyright © 2020. Published by Elsevier B.V.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Flavonoids
• NLR Family, Pyrin Domain-Containing 3 Protein
• Neuroprotective Agents
• poncirin
• NADPH Oxidase 4
• Nox4 protein, rat
• Glucose
• Oxygen

Topics

• Animals
• Animals, Newborn
• Anti-Inflammatory Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Survival (drug effects)
• Cells, Cultured
• Cerebral Cortex (cytology)
• Cytokines (metabolism)
• Flavonoids (pharmacology)
• Glucose
• Mitochondria (drug effects, physiology)
• NADPH Oxidase 4 (genetics, metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Neurons (drug effects, metabolism)
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects)
• Oxygen
• Rats, Sprague-Dawley
• Reperfusion Injury (genetics, metabolism)
• Rats