Kang Ze-Chun, Wang Hai-Gang, Yang Yu-Lin, Zhao Xiao-Yue, Zhou Qi-Meng, Yang Ying-Lin, Yang Jing-Yu, Du Guan-Hua
Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang City, Liaoning Province, People's Republic of China.
Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Drug Des Devel Ther. 2020 Sep 4;14:3577-3587. doi: 10.2147/DDDT.S249176. eCollection 2020.
As a substrate of apoER2, Reelin has been verified to exert neuroprotection by preventing memory impairment. Pinocembrin is the most abundant natural flavonoid found in propolis, and it has been used to exert neuroprotection, blood-brain barrier protection, anti-oxidation, and inflammation diminishing, both in vitro and in vivo. However, the roles and molecular mechanisms of pinocembrin in neurobehavioral outcomes and neuronal repair after vascular dementia are still under investigation.
To explore the role of pinocembrin in the involvement of the Reelin-dab1 signaling pathway in improving memory impairment, both in cell culture and animals experiments.
Behavioral tests were conducted on day 48 to confirm the protection of pinocembrin against cognitive impairment. Cell and molecular biology experiments demonstrated that the Reelin-dab1 pathway mediates the underlying mechanism of cognitive improvement by pinocembrin.
It was showed that pinocembrin alleviated learning and memory deficits induced by vascular dementia, by inducing the expression of Reelin, apoER2, and p-dab1 in the hippocampus. The expression of Reelin and p-dab1 was both inhibited following Reelin RNA interference in SH-SY5Y prior to oxygen glucose deprivation (OGD) injury, suggesting that Reelin played a core role in pinocembrin's effect on OGD in vitro.
Pinocembrin improves the cognition via the Reelin-dab1 signaling pathway.
作为载脂蛋白E受体2(apoER2)的底物,Reelin已被证实可通过预防记忆障碍发挥神经保护作用。白杨素是蜂胶中含量最丰富的天然黄酮类化合物,已被用于在体外和体内发挥神经保护、血脑屏障保护、抗氧化和减轻炎症的作用。然而,白杨素在血管性痴呆后神经行为结果和神经元修复中的作用及分子机制仍在研究中。
在细胞培养和动物实验中,探讨白杨素在Reelin-dab1信号通路参与改善记忆障碍中的作用。
在第48天进行行为测试,以确认白杨素对认知障碍的保护作用。细胞和分子生物学实验表明,Reelin-dab1通路介导了白杨素改善认知的潜在机制。
结果显示,白杨素通过诱导海马中Reelin、apoER2和磷酸化dab1(p-dab1)的表达,减轻了血管性痴呆诱导的学习和记忆缺陷。在氧糖剥夺(OGD)损伤前,对SH-SY5Y细胞进行Reelin RNA干扰后,Reelin和p-dab1的表达均受到抑制,这表明Reelin在白杨素对体外OGD的影响中起核心作用。
白杨素通过Reelin-dab1信号通路改善认知。