Luteolin Enhances Endothelial Barrier Function and Attenuates Myocardial Ischemia–Reperfusion Injury via FOXP1-NLRP3 Pathway

TL;DR

Luteolin, a natural flavonoid, protects the heart from injury during blood flow restoration by improving blood vessel integrity and reducing inflammation.

Contribution

This study identifies the FOXP1-NLRP3 pathway as a novel mechanism through which luteolin protects against heart injury.

Findings

Luteolin improved heart function and reduced vascular leakage in a rat model of heart injury.

Luteolin's effects were blocked when FOXP1 was silenced, confirming its role in the protective mechanism.

NLRP3 inhibition mimicked luteolin's protective effects, linking inflammation suppression to its benefits.

Abstract

As a natural flavonoid, the flavonoid luteolin is characterized by its powerful antioxidant and anti-inflammatory effects. While its precise mechanisms require further elucidation, existing evidence confirms its efficacy in ameliorating myocardial ischemia–reperfusion injury (MIRI). This research was designed to investigate the mechanism through which luteolin protects against MIRI. We established MIRI rat models through the ligation of left anterior descending coronary artery (LAD). To evaluate the cardioprotective effects of luteolin, echocardiographic analysis was performed, Hematoxylin and Eosin (HE) staining, and serum cardiac injury markers creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH). Cardiac vascular permeability was determined using Evans blue staining. To mimic ischemia–reperfusion injury, endothelial cells (ECs) were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro. Endothelial cell barrier function was evaluated through F-actin phalloidin staining and FITC-Dextran fluorescence leakage experiments. To elucidate the molecular mechanism, FOXP1 small interfering RNA (siRNA) and NLRP3 inhibitor MCC950 were administered. In MIRI rats, luteolin significantly improved cardiac function and preserved endothelial barrier integrity. These effects were associated with upregulation of FOXP1 and suppression of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. In OGD/R-treated endothelial cells, luteolin restored barrier function and cell viability. The protective effects of luteolin were abolished after FOXP1 silencing. Pharmacological NLRP3 inhibition (MCC950) mirrored luteolin’s protection. Our study indicates that luteolin enhances endothelial barrier function and attenuates MIRI via the FOXP1-NLRP3 pathway. The current study provides a potential drug for MIRI treatment.

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