5-HMF attenuates striatum oxidative damage via Nrf2/ARE signaling pathway following transient global cerebral
Bai-Liu Ya1, Hong-Fang Li2, Hai-Ying Wang1
1Department of Physiology, Jining Medical University, 16 He-hua Street, Bei-hu District, Jining, Shandong, 272067, People's Republic of China.
Abstract:
Recent studies have shown 5-hydroxymethyl-2-furfural (5-HMF) has favorable biological effects, and its neuroprotection in a variety of neurological diseases has been noted. Our previous study showed that treatment of 5-HMF led to protection against permanent global cerebral ischemia. However, the underlying mechanisms in cerebral ischemic injury are not fully understood. This study was conducted to investigate the neuroprotective effect of 5-HMF and elucidate the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway mechanism in the striatum after transient global cerebral ischemia. C57BL/6 mice were subjected to bilateral common carotid artery occlusion for 20 min and sacrificed 24 h after reperfusion. 5-HMF (12 mg/kg) or an equal volume of vehicle was intraperitoneally injected 30 min before ischemia and 5 min after the onset of reperfusion. At 24 h after reperfusion, neurological function was evaluated by neurological disability status scale, locomotor activity test and inclined beam walking test. Histological injury of the striatum was observed by cresyl violet staining and terminal deoxynucleotidyl transferase (TdT)-mediated dNTP nick end labeling (TUNEL) staining. Oxidative stress was evaluated by the carbonyl groups introduced into proteins, and malondialdehyde (MDA) levels. An enzyme-linked immunosorbent assay (ELISA)-based measurement was used to detect Nrf2 DNA binding activity. Nrf2 and its downstream ARE pathway protein expression such as heme oxygenase-1, NAD (P)H:quinone oxidoreductase 1, glutamate-cysteine ligase catalytic subunit and glutamate-cysteine ligase modulatory subunit were detected by western blot. Our results showed that 5-HMF treatment significantly ameliorated neurological deficits, reduced brain water content, attenuated striatum neuronal damage, decreased the carbonyl groups and MDA levels, and activated Nrf2/ARE signaling pathway. Taken together, these results demonstrated that 5-HMF exerted significant antioxidant and neuroprotective effects following transient cerebral ischemia, possibly through the activation of the Nrf2/ARE signaling pathway.
Insights
5-hydroxymethylfurfural (5-HMF) demonstrates neuroprotective effects against cerebral ischemia by activating the Nrf2/ARE pathway. This compound reduces neuronal damage and oxidative stress, offering a potential therapeutic strategy for stroke recovery.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- 5-hydroxymethyl-2-furfural (5-HMF) exhibits beneficial biological effects, including neuroprotection.
- Previous research indicated 5-HMF protects against permanent global cerebral ischemia.
- The precise mechanisms underlying 5-HMF's neuroprotection in cerebral ischemic injury require further elucidation.
Purpose of the Study:
- To investigate the neuroprotective effect of 5-HMF in transient global cerebral ischemia.
- To elucidate the role of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway in 5-HMF-mediated neuroprotection.
Main Methods:
- C57BL/6 mice underwent transient global cerebral ischemia via bilateral common carotid artery occlusion.
- 5-HMF was administered intraperitoneally before ischemia and reperfusion.
- Neurological function, striatal histological injury, oxidative stress markers (carbonyl groups, MDA), and Nrf2/ARE pathway activation (ELISA, Western blot) were assessed.
Main Results:
- 5-HMF treatment significantly improved neurological function and reduced brain water content.
- Histological analysis revealed attenuated striatal neuronal damage and decreased oxidative stress markers.
- 5-HMF administration activated the Nrf2/ARE signaling pathway, increasing the expression of downstream proteins like heme oxygenase-1.
Conclusions:
- 5-hydroxymethylfurfural (5-HMF) exerts significant antioxidant and neuroprotective effects following transient cerebral ischemia.
- The Nrf2/ARE signaling pathway is likely a key mechanism mediating the neuroprotective actions of 5-HMF.
- These findings suggest 5-HMF as a promising therapeutic candidate for managing cerebral ischemic injury.
