Licochalcone B attenuates neuronal injury through anti-oxidant effect and enhancement of Nrf2 pathway in MCAO rat model of stroke

• Published in: International immunopharmacology Vol. 100; p. 108073
• Main Authors: Zhou, Baosheng, Wang, Honglin, Zhang, Bo, Zhang, Lianlian
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2021; Elsevier BV
• Subjects: Animals; Antioxidants; Antioxidants - pharmacology; Antioxidants - therapeutic use; Apoptosis; Apoptosis - drug effects; Apoptosis - immunology; Biochemical analysis; Brain-derived neurotrophic factor; Cerebral blood flow; Cerebral infarction; Chalcones - pharmacology; Chalcones - therapeutic use; Disease Models, Animal; Evaluation; Gene Knockdown Techniques; Hippocampus - drug effects; Hippocampus - immunology; Hippocampus - pathology; Humans; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - immunology; Infarction, Middle Cerebral Artery - pathology; Inflammation; Injuries; Interleukin 4; Ischemia; Ischemic stroke; Licochalcone B; Male; Middle cerebral artery occlusion; Nerve growth factor; Neurological diseases; Neuronal injury; Neurons - drug effects; Neurons - immunology; Neurons - pathology; Neuroprotection; NF-E2-Related Factor 2 - agonists; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Nitric-oxide synthase; Occlusion; Oxidants; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - immunology; Oxidizing agents; Rats; Signal Transduction - drug effects; Signal Transduction - genetics; Signal Transduction - immunology; Stroke; Tumor necrosis factor-α; Vitamin C; Neuronal injury; Oxidative stress; Ischemic stroke; Licochalcone B; Middle cerebral artery occlusion
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2021.108073

•First study reported the neuroprotective effects of Licochalcone B (Lico B) in stroke model.•Confirm the anti-oxidant and anti-inflammatory effects of Lico B.•Proposed a potential mechanism that Lico B activated the Nrf2 pathway. Investigating anti-oxidant therapies that lead to the diminution of oxidative injury is priority in clinical. We herein aimed to explore whether and how Licochalcone B (Lico B) act as an anti-oxidant in the stroke model. Middle cerebral artery occlusion (MCAO) was constructed as stroke model and exposed to various doses of Lico B. Behavioral tests and neurological behavior status were detected for neurological function examination. Histological staining was used for evaluating cerebral injury, and neuronal apoptosis or damage. Levels of oxidative stress and inflammation were also assessed by biochemical analysis and expression analysis. Nrf2 knockdown induced by lentiviral vector was used for the research on mechanism. Lico B had improvement effects on cerebral infarction size, memory impairments, and neurological deficits after MCAO. Histological evaluation also revealed the amelioration of neuronal injury and apoptosis by Lico B, along with down-regulation of apoptosis-related proteins. Additionally, Lico B rescued the down-regulation of BDNF and NGF after MCAO. Moreover, Lico B suppressed the oxidative stress and inflammation, manifesting as the enhancement of SOD, GSH and IL-4, but the decline of MDA, iNOS, and TNF-α. Finally, Nrf2 knockdown reversed the Lico B-caused improvement in neuronal injury, apoptosis and oxidative stress levels. The present study revealed the neuroprotective effects of Lico B in MCAO rats. Importantly, we proposed a potential mechanism that Lico B activated the Nrf2 pathway, thereby acting as anti-oxidant to attenuate neuronal injury and apoptosis after stroke. The proposed mechanism provided an encouraging possibility for anti-oxidant therapy of stroke.