Department of Neurosurgery, Tianjin First Central Hospital, Tianjin, China.
Department of Interventional Medicine, Dazhou Central Hospital, Dazhou, China.
Int Immunopharmacol. 2021 Nov;100:108073. doi: 10.1016/j.intimp.2021.108073. Epub 2021 Aug 25.
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.
研究导致氧化损伤减少的抗氧化疗法是临床的首要任务。我们旨在探讨lico 查尔酮 B（lico B）是否以及如何作为抗氧化剂在中风模型中发挥作用。
构建大脑中动脉闭塞（MCAO）作为中风模型，并暴露于不同剂量的lico B。行为测试和神经行为状态用于神经功能检查。组织学染色用于评估脑损伤、神经元凋亡或损伤。通过生化分析和表达分析评估氧化应激和炎症水平。使用慢病毒载体诱导 Nrf2 敲低用于研究机制。
Lico B 对 MCAO 后大脑梗死面积、记忆障碍和神经功能缺损有改善作用。组织学评价还显示 Lico B 改善了神经元损伤和凋亡，并下调了凋亡相关蛋白。此外，Lico B 挽救了 MCAO 后 BDNF 和 NGF 的下调。此外，Lico B 抑制氧化应激和炎症，表现为 SOD、GSH 和 IL-4 的增强，而 MDA、iNOS 和 TNF-α的下降。最后，Nrf2 敲低逆转了 Lico B 引起的神经元损伤、凋亡和氧化应激水平的改善。
本研究揭示了 Lico B 在 MCAO 大鼠中的神经保护作用。重要的是，我们提出了一种潜在的机制，即 Lico B 激活了 Nrf2 通路，从而作为抗氧化剂减轻中风后神经元损伤和凋亡。所提出的机制为中风的抗氧化治疗提供了一个令人鼓舞的可能性。
