Abstract
Stroke represents one of the main causes of disability and death worldwide. The pathological subtypes of stroke are ischemic stroke, the most frequent, and hemorrhagic stroke. Nrf2 is a transcription factor that regulates redox homeostasis. In stress conditions, Nrf2 translocates inside the nucleus and induces the transcription of enzymes involved in counteracting oxidative stress, endobiotic and xenobiotic metabolism, regulators of inflammation, and others. Different natural compounds, including food and plant-derived components, were shown to be able to activate Nrf2, mediating an antioxidant response. Some of these compounds were tested in stroke experimental models showing several beneficial actions. In this review, we focused on the studies that evidenced the positive effects of natural bioactive compounds in stroke experimental models through the activation of Nrf2 pathway. Interestingly, different natural compounds can activate Nrf2 through multiple pathways, inducing a strong antioxidant response associated with the beneficial effects against stroke. According to several studies, the combination of different bioactive compounds can lead to a better neuroprotection. In conclusion, natural bioactive compounds may represent new therapeutic strategies against stroke.
Highlights
Stroke represents the second cause of death and one of the main causes of disability
We focused on the studies performed on in vivo and in vitro stroke models, that evaluated the protective effects of natural compounds through the activation of Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway
The results suggested that ginseng pretreatment may exert protection after permanent distal MCA occlusion (MCAO) and Nrf2 pathway had a role in its protective effects [92]
Summary
Stroke represents the second cause of death and one of the main causes of disability. The mass effect caused by hematoma and the possible interruption of cerebrospinal fluid circulation in case of subarachnoid or intraventricular bleeding, causes an increase in intracranial pressure. In this case tPA can induce hematoma dissolution and restore cerebrospinal fluid circulation. In the case of hemorrhagic stroke other than the primary damage caused by the hematoma mass effect, the second injury has a fundamental role, because of the onset of the pro-inflammatory cascade and the oxidative stress [6]. Oxidative stress, indicated as an alteration between reactive oxygen species (ROS) production and elimination, plays a main role in stroke For this reason, counteracting oxidative stress could be considered as a potential therapeutic approach. In order to select the studies, we performed a PubMed search using the keywords “stroke” and “Nrf2,” considering the experimental studies published from 2015 that evaluated in in vivo stroke models, both in vivo and in vitro stroke models or in microglia and astrocyte in vitro models the efficacy of the natural compounds showing the involvement of Nrf
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