Galangin attenuated cerebral ischemia-reperfusion injury by inhibition of ferroptosis through activating the SLC7A11/GPX4 axis in gerbils

Insight into Crosstalk between Ferroptosis and Necroptosis: Novel Therapeutics in Ischemic Stroke

“…Oxidative Medicine and Cellular Longevity [192] Xinshao formula MCAO/R rats Increases the activity of SOD and GPX4; decreases the activity of inducible nitric oxide synthase and the content of NO, ROS, and MDA [196] Carthamin yellow MCAO/R rats Decreases Fe (II) and ROS accumulation and MDA lever; increases GSH and GPX4 lever [110] Edaravone MCAO/R rats Reduces ROS generation, cerebral infarct size, and neurological defects [198] Necroptosis Cyclosporine-A BBCAO/R rats Inhibits MPTP opening; reduces RIP1 and RIP3 levels [199] Nec-1 MCAO/R rats Suppresses RIP1-RIP3 interaction and RIP3 activation; decreases the dead rate of neurons in the hippocampal CA1 region [200] β-Caryophyllene OGD/R neuron cell; MCAO/R mice Decreases TNF-α, IL-1β, and toll-like receptor 4 levels; decreases RIP1 and RIP3 expression and MLKL phosphorylation [202] Emricasan +ponatinib MCAO/R rats Decreases RIP1, RIP3, and MLKL expression; reduces the activity of caspase-8 [203] 9 Oxidative Medicine and Cellular Longevity Epac1, which improves cerebral blood flow and promotes neurite outgrowth following ischemic stroke [172]. Ferroptosis is also suppressed by lipophilic antioxidants, including statins and vitamin B12.…”

“…Oxidative stress plays a major role in the pathogenesis of CIRI. Some pharmacotherapies, such as metformin [ 191 ] and galangin [ 192 ], suppress ferroptosis and exert cerebroprotective effects in the context of CIRI by decreasing lipid peroxidation production or increasing the expression of GPX4. Apart from that efficacy, metformin (1,1-Dimethylbiguanide), a hypoglycemic drug, leads to glucose starvation which results in the phosphorylation and activation of adenosine 5′-monophosphate-activated protein kinase (AMPK) [ 193 , 194 ].…”

Emerging Role of Ferroptosis in the Pathogenesis of Ischemic Stroke: A New Therapeutic Target?

“…Naotaifang extract improved neural functions in rats after ischemia by inhibiting neuronal ferroptosis through downregulation of TFR1/DMT1 and upregulation of SCL7A11/GPX4 pathways ( Lan et al, 2020 ). In addition, Galangin, a flavonoid isolated from Alpinia officinarum , attenuated cerebral IR injury by inhibiting ferroptosis via activating the SLC7A11 and GPX4 in gerbils ( Guan et al, 2021 ). Although these traditional Chinese drugs have not been clinically verified to improve patients’ conditions after ischemic stroke, their safety and lack of toxicity may facilitate their testing in clinical trials and application to patients.…”

Ferroptosis: A Novel Therapeutic Target for Ischemia-Reperfusion Injury

“…Deferoxamine treatment immediately after brain reperfusion decreases infarct volume ( Hanson et al, 2009 ), and suppressing tau, a protein of Alzheimer’s disease, protects against cerebral ischemia-reperfusion injury in young mice via ferroptosis inhibition, with ferroptosis inhibitors, such as liproxstatin-1 and Fer-1, reviving the protection provided by tau knockout in older mice ( Tuo et al, 2017 ). Galangin cloud improves the learning ability and memory in gerbils after I/R injury by inhibiting ferroptosis through increased SLC7A11 and GPX4 expressions ( Guan et al, 2021 ), suggesting that the protective effect of galangin on cerebral I/R injury is affected through the inhibition of ferroptosis. Carvacrol, a monoterpenoid phenol, also protects hippocampal neurons against I/R injury by increasing the expression of GPX4 ( Guan et al, 2019 ).…”