Protective effects of leonurine against ischemic stroke in mice by activating nuclear factor erythroid 2‐related factor 2 pathway

Abstract

Aims Leonurine has been shown to trigger antioxidant responses during ischemic stroke, and nuclear factor erythroid 2‐related factor 2 (Nrf‐2) imparts protective effects against oxidative injury. The present study has determined that leonurine prevents ischemic injury of brain tissues via Nrf‐2 pathway activation. Methods Male ICR mice and Nrf‐2−/− mice were subjected to permanent middle cerebral artery occlusion (pMCAO) and received leonurine treatment at 2 hours after pMCAO by intraperitoneal injection. Neurological deficit scores as well as infarct volume were assessed to determine the neuroprotective role of leonurine. Nrf‐2 was investigated using Western blotting and real‐time polymerase chain reaction (RT‐PCR) analysis to elucidate the neuroprotective mechanism of leonurine. Commercial kits were employed to determine reactive oxygen species (ROS), superoxide (SOD), catalase (CAT), glutathione peroxidase (GSH‐Px), malonaldehyde (MDA), and glutathione (GSH). Vascular endothelial growth factor (VEGF) was evaluated by Western blotting and RT‐PCR analysis, and VEGF was localized using immunofluorescence. Results The application of leonurine on ICR mice resulted in an improvement in neurological deficit scores and a reduction in infarct volume. Leonurine upregulated nuclear Nrf‐2 protein and increased total Nrf‐2 protein expression and mRNA levels. Leonurine regulated SOD, MDA, CAT, GSH, and GSH‐Px, and it significantly inhibited ROS production in ICR mice. Leonurine improved VEGF expression and increased VEGF expression in neurons, astrocytes, and endothelial cells. However, leonurine had no obvious beneficial effects on Nrf‐2−/− mice. Conclusions Leonurine exerted neuroprotective effects, promoted antioxidant responses, and upregulated VEGF expression by activating the Nrf‐2 pathway.

Inhibition of Acyl-CoA Synthetase Long-Chain Family Member 4 Facilitates Neurological Recovery After Stroke by Regulation Ferroptosis

“…Reduced glutathione and total glutathione/oxidized glutathione are the main dynamic indicators of cellular redox status ( Aquilano et al, 2014 ). Furthermore, GPx is a specific catalase for the hydrogen peroxide reduction of reduced glutathione and its activity represents the rate at which GSH is catalyzed ( Xie et al, 2019 ). In this study, GPx activity, GSH levels, GSH/GSSG ratio, and SOD levels were decreased in stroke patients, but MDA levels and LPO levels were increased.…”

Nrf2/HO-1 mediates neuroprotective effects of pramipexole by attenuating oxidative damage and mitochondrial perturbation after traumatic brain injury

“…It also binds to specific deoxyribonucleic acid antioxidant response elements (AREs) to initiate the transcription of cytoprotective genes such as heme oxygenase-1 ( HO-1 ; also known as Hmox1 ), superoxide dismutase family members (SODs) and glutathione reductase ( Gsr ) in the nucleus ( Chen et al, 2018 ). It has been reported that an increased level of Nrf2 exerts neuroprotective effects in TBI ( Caglayan et al, 2019 ) and neurodegenerative diseases due to amelioration of oxidative damage ( Xie et al, 2019 ). Thus, modulation of Nrf2 is a potential strategy to attenuate TBI-induced oxidative damage and mitochondrial dysfunction.…”

Oxidative Stress at the Crossroads of Aging, Stroke and Depression

“…Thirdly, antioxidant systems also exert protective effects on blood vessels. For instance, ginkgolide [ 166 ] and leonurine [ 167 ] promote angiogenesis via upregulated VEGF expression. Fourthly, BBB integrity can be protected by several antioxidants, including astragaloside IV [ 168 ], Osthole [ 169 ] and the Chinese herbal medicine formula, Tao Hong Si Wu Decoction[ 170 , 171 ].…”