Chemico-biological interactionsFeb 19, 2018

Isoquercetin reduces cell damage and nerve cell death after blood flow loss and return by activating protective cell defense pathways

Updated Apr 5, 2026

Abstract

Rats treated with Isoquercetin exhibited a lower degree of infarct volume and brain water content compared to vehicle-treated rats.

Isoquercetin treatment improved neurological deficits as evidenced by a decreased modified neurological severity score in MCAO/R rats.
Treatment reduced the production of reactive oxygen species (ROS) and malondialdehyde (MDA), while increasing the activity of superoxide dismutase (SOD) and catalase (CAT) in the brains of MCAO/R rats.
Isoquercetin prevented ischemia/reperfusion-induced neuronal apoptosis, indicated by increased cell viability and a decrease in TUNEL-positive cells.
The anti-apoptotic effects of Isoquercetin were associated with downregulation of cleaved caspase-3 protein and upregulation of Bcl-2 protein.
Nrf2 knockdown diminished the protective effects of Isoquercetin in primary cultures of rat hippocampal neurons exposed to oxygen and glucose deprivation.
Isoquercetin activated the NOX4/ROS/NF-κB signaling pathway and induced Nrf2 translocation in primary culture of rat hippocampal neurons.

Simplified

Isoquercetin (Iso) has been found to have neuroprotective effects against cerebral ischemic stroke. However, the exact molecular mechanism underlying its neuroprotective ability remains unclear. In this study, we aimed to evaluate the neuroprotective effects of Iso in primary culture of rat hippocampal neurons exposed to oxygen and glucose deprivation and reperfusion (OGD/R) injury and in rats subjected to middle cerebral artery occlusion and reperfusion (MCAO/R) injury. We found that rats treated with Iso exhibited a lower degree of infarct volume, and brain water content than the vehicle-treated rats. Treatment with Iso also improved the neurological deficits in MCAO/R rats as shown by the decreased modified neurological severity score. Iso treatment decreased the reactive oxygen species (ROS) and malondialdehyde (MDA) production, and increased the activity of superoxide dismutase (SOD) and catalase (CAT) in brains of MCAO/R rats and primary culture of rat hippocampal neurons exposed to OGD/R. Iso treatment prevents I/R-induced neuronal apoptosis in vivo and in vitro as indicated by increased cell viability and decreased number of TUNEL-positive cells, accompanying with downregulation of cleaved caspase-3 protein and upregulation of Bcl-2 protein. Moreover, Nrf2 knockdown weakened the anti-apoptotic and anti-oxidant activities of Iso in primary culture of rat hippocampal neurons exposed to OGD/R. Interestingly, we found that Iso could induce Nrf2 translocation from cytoplasm to nucleus in primary culture of rat hippocampal neurons exposed to OGD/R. Iso activated the NOX4/ROS/NF-κB signaling pathway in in vivo and in vitro cerebral I/R injury models. Nrf2 knockdown blocked the inhibitory effect of Iso on protein expression of NOX4, p-IκBα and p-p65 in primary culture of rat hippocampal neurons exposed to OGD/R. All the data suggested that Iso protected against oxidative stress and neuronal apoptosis in in vivo and in vitro cerebral I/R injury models via Nrf2-mediated inhibition of the NOX4/ROS/NF-κB signaling pathway. Our findings suggested that Iso could be a potential agent for I/R brain injury.

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