Luteolin-7-O-β-d-Glucuronide Attenuated Cerebral Ischemia/Reperfusion Injury: Involvement of the Blood-Brain Barrier

• Published in: Biomedicines Vol. 12; no. 6; p. 1366
• Main Authors: Fan, Xing, Song, Jintao, Zhang, Shuting, Lu, Lihui, Lin, Fang, Chen, Yu, Li, Shichang, Jin, Xinxin, Wang, Fang
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19-06-2024; MDPI
• Subjects: Angina; Angina pectoris; Animal experimentation; Antibodies; Apoptosis; Basement membranes; Blood-brain barrier; Brain; Brain injury; Cardiovascular disease; Carotid arteries; Cerebral blood flow; Cerebral cortex; Cerebral infarction; cerebral ischemia/reperfusion; Cerebrospinal fluid; Cerebrovascular diseases; Coronary artery disease; Endothelial cells; Experiments; Flavonoids; Heart diseases; Herbal medicine; inflammation; Intravenous administration; Ischemia; Laboratory animals; luteolin-7-O-β-D-glucuronide; Medicine, Botanic; Medicine, Herbal; Membrane degradation; Membrane permeability; Metalloproteinase; middle cerebral artery occlusion; Morbidity; Myocardial infarction; Neurons; Permeability; Proteins; Quality of life; Reperfusion; S100b protein; Stroke; Tumor necrosis factor-α; Veins & arteries; Water content; China; cerebral ischemia/reperfusion; blood–brain barrier; luteolin-7-O-β-D-glucuronide; inflammation; middle cerebral artery occlusion
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines12061366

Ischemic stroke is a common cerebrovascular disease with high mortality, high morbidity, and high disability. Cerebral ischemia/reperfusion injury seriously affects the quality of life of patients. Luteolin-7-O-β-d-glucuronide (LGU) is a major active flavonoid compound extracted from
Hance, a Chinese medicinal herb mainly used for the treatment of coronary heart disease, angina pectoris, cerebral infarction, etc. In the present study, the protective effect of LGU on cerebral ischemia/reperfusion injury was investigated in an oxygen-glucose deprivation/reoxygenation (OGD/R) neuronal model and a transient middle cerebral artery occlusion (tMCAO) rat model. In in vitro experiments, LGU was found to improve the OGD/R-induced decrease in neuronal viability effectively by the MTT assay. In in vivo experiments, neurological deficit scores, infarction volume rates, and brain water content rates were improved after a single intravenous administration of LGU. These findings suggest that LGU has significant protective effects on cerebral ischemia/reperfusion injury in vitro and in vivo. To further explore the potential mechanism of LGU on cerebral ischemia/reperfusion injury, we performed a series of tests. The results showed that a single administration of LGU decreased the content of EB and S100B and ameliorated the abnormal expression of tight junction proteins ZO-1 and occludin and metalloproteinase MMP-9 in the ischemic cerebral cortex of the tMCAO 24-h injury model. In addition, LGU also improved the tight junction structure between endothelial cells and the degree of basement membrane degradation and reduced the content of TNF-α and IL-1β in the brain tissue. Thereby, LGU attenuated cerebral ischemia/reperfusion injury by improving the permeability of the blood-brain barrier. The present study provides new insights into the therapeutic potential of LGU in cerebral ischemia.