Abstract
BackgroundMorbidity and mortality remain high for ischemic stroke victims, and at present these patients lack effective neuroprotective agents, which improve the cure rate. In recent years, studies have shown that pelargonidin has many biological actions. However, few studies are available regarding the pelargonidin treatment of cerebral ischemia.MethodsThe rat middle cerebral artery occlusion (MCAO) model was established to investigate the neuroprotective effect of pelargonidin on cerebral ischemia/reperfusion injury. Reperfusion was performed 2 h after ischemia; magnetic resonance imaging (MRI) and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining were used to measure the volume of cerebral ischemia. Both modified neurological severity scores (mNSSs) and Morris water maze test were used to assess the neurological functions. ELISA was applied to determine the levels of TNF-α, TGF-β, IL-6, IL-10, MDA, and SOD. The expression of Nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) protein in brain tissue was measured by immunofluorescence and Western blot assays.ResultsThe results showed that pelargonidin could effectively reduce the volume of cerebral ischemia and improve the neurological function in MCAO rats, thereby improving memory and learning ability. With the corresponding decreases in the expression of TNF-α, TGF-β, IL-6, and MDA, the level of IL-10 and SOD increased and also promoted the nuclear metastasis of Nrf2 and the expression of HO-1 in ischemic brain tissues.ConclusionsOur data demonstrated that pelargonidin ameliorated neurological function deficits in MCAO rats, and its potential mechanism of action was associated with overexpression of the Nrf2/HO-1-signaling pathway. This study will provide a new approach to treat cerebral ischemia/reperfusion injury.
Highlights
Stroke is a group of diseases associated with sudden rupture of cerebral vessels or brain tissue injury caused by blockage of blood flow to the brain and is characterized by high morbidity, mortality, and disability rates
The results showed that pelargonidin could effectively reduce the volume of cerebral ischemia and improve the neurological function in middle cerebral artery occlusion (MCAO) rats, thereby improving memory and learning ability
We found that pelargonidin could decrease the levels of MDA, TNF-α, TGF-β, and IL-6 in the serum of MCAO rats and elevate the expression of SOD and IL-10
Summary
Stroke is a group of diseases associated with sudden rupture of cerebral vessels or brain tissue injury caused by blockage of blood flow to the brain and is characterized by high morbidity, mortality, and disability rates. Pelargonidin relieves brain ischemia/reperfusion injury via Nrf2/HO-1 pathway 21 effective way to restore blood supply in ischemic stroke, only about 3–5% of ischemic stroke patients are effectively treated due to a narrow time window for r-tPA treatment [6,7,8]. It has been shown that Nrf activation attenuated oxidative damage induced by cerebral ischemic injury and that HO-1-deficient mice exhibited more severe brain injury [16,17]. The potential biological activities and mechanism of pelargonidin as an antioxidant and anti-inflammatory factor in cerebral ischemia/reperfusion (I/R) injury remain unclear. Our study showed that pelargonidin could effectively reduce the infarct area, improve neurological functions, significantly reduce the level of inflammatory and oxidative factors, and promote the repair of neuronal cells in brain tissue after cerebral I/R. The neuroprotective effect of pelargonidin on cerebral I/R injury was associated with overexpression of the Nrf2/ HO-1 pathway
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