5-HMF plays an intervention role in ischemic stroke by regulating GluR2 to improve mitochondrial function and promote angiogenesis

Abstract

Introduction

5-Hydroxymethyl furfural (5-HMF) is a furan compound with a molecular formula of C₆H₆O₃. Studies have found that 5-HMF has many pharmacological effects, such as improving hemorheology, anti-inflammatory, antioxidant activity and anti-myocardial ischemia. Identifying the preventive effect of 5-HMF against ischemic stroke and its possible mechanism was the aim of this investigation.

Methods

The MCAO animal model was used to detect the related indexes of behavior, neurological function and mitochondrial function, and to clarify the effect of 5-HMF on ischemic stroke. The HBMECs model induced by OGD-R was intervened by 5-HMF, and the GluR2 silencing sequence was added to detect mitochondrial function and angiogenesis-related indicators, so as to further explore the mechanism of 5-HMF intervention in ischemic stroke.

Results

In the MCAO experiment, the behavioral results showed that 5-HMF increased the quantity of autonomic activities, increased the exercise time and distance, reduced the balance beam score, and prolonged the residence time of MCAO rats on the rotating rod (P < 0.01). The results of neurological function indicated that 5-HMF reduced the neurological function score, increased the blood flow velocity of middle cerebral artery (P < 0.01), reduced the area of cerebral infarction, and alleviated the damage of cerebral cortex and hippocampal neurons. The results of mitochondrial function indicated that 5-HMF could significantly reduce the apoptosis of primary brain cells, ROS, Ca²⁺ levels, increase mitochondrial membrane potential and GluR2 expression in MCAO rats (P < 0.01). In the OGD-R-induced HBMECs experiment, 5-HMF increased the expression level of GluR2, increased cell viability, and decreased LDH activity in cell supernatant (P < 0.01). The results of mitochondrial function showed that 5-HMF reduced the levels of Ca²⁺ and glutamate in the cell supernatant, reduced the levels of apoptosis and ROS, increased the mitochondrial membrane potential, and improved the expression of mitochondrial dynamics-related proteins (P < 0.05 or P < 0.01). These improvements were markedly reversed after the addition of GluR2 silencing sequence (P < 0.01).

Conclusions

5-HMF has the effect of ameliorating brain damage in MCAO rats, and by regulating the expression of GluR2, reducing intracellular Ca²⁺ concentration, improving mitochondrial function, promoting angiogenesis, thereby reducing OGD-R-induced HBMECs damage.