Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China.
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China.
Int Immunopharmacol. 2019 Aug;73:304-311. doi: 10.1016/j.intimp.2019.05.033. Epub 2019 May 22.
Microglia-mediated neuroinflammation is an important contributor to the pathogenesis of neurodegenerative diseases. Inhibition of neuroinflammation has been proved to be effective in neurodegenerative diseases treatment. Nuclear factor erythroid 2 related factor 2 (Nrf2) is a key mediator of endogenous inducible defense systems in the body. In response to oxidative stress, Nrf2 translocates to the nucleus and binds to specific DNA sites termed as anti-oxidant response elements to initiate transcription of cytoprotective genes, such as hemeoxygenase-1 (HO-1) and nicotinamide adenine dinucleotide phosphate: quinine oxidoreductase-1 (NQO1). However, insufficient Nrf2 activation has been closely associated with the progress of neurodegenerative diseases. New findings have linked activation of Nrf2 signaling to anti-inflammatory effects. Icariin (ICA), a natural compound derived from Herba Epimedii, possesses amounts of pharmacological activities, such as anti-aging, anti-oxidation and anti-inflammatory effects. Recent studies have confirmed that ICA exerted neuroprotection against neurodegenerative diseases. However, the mechanisms underlying ICA-mediated neuroprotection were not fully understood. In the present study, microglia BV-2 cell lines were performed to investigate the anti-neuroinflammatory effects of ICA and the mechanisms of actions. Results showed that ICA suppressed lipopolysaccharide (LPS)-induced microglial pro-inflammatory factors production. In addition, activation of Nrf2 signaling pathway participated in ICA-mediated anti-neuroinflammation, as evidenced by the following observations. First, Nrf2 siRNA reversed ICA-reduced microglial activation and pro-inflammatory factors release. Second, a selective inhibitor of HO-1 abolished ICA-mediated anti-neuroinflammatory actions. This study will give us an insight into the potential of Nrf2 and neuroinflammation in terms of opening up an alternative therapeutic strategy for neurodegenerative diseases.
小胶质细胞介导的神经炎症是神经退行性疾病发病机制的重要因素。抑制神经炎症已被证明在神经退行性疾病的治疗中是有效的。核因子红细胞 2 相关因子 2 (Nrf2) 是体内内源性诱导防御系统的关键介质。在氧化应激的情况下，Nrf2 易位到细胞核并与称为抗氧化反应元件的特定 DNA 位点结合，从而启动细胞保护基因，如血红素加氧酶-1 (HO-1) 和烟酰胺腺嘌呤二核苷酸磷酸：醌氧化还原酶-1 (NQO1) 的转录。然而，Nrf2 的激活不足与神经退行性疾病的进展密切相关。新的发现将 Nrf2 信号的激活与抗炎作用联系起来。淫羊藿苷（ICA）是一种从淫羊藿中提取的天然化合物，具有多种药理活性，如抗衰老、抗氧化和抗炎作用。最近的研究证实，ICA 对神经退行性疾病具有神经保护作用。然而，ICA 介导的神经保护作用的机制尚不完全清楚。在本研究中，采用小胶质细胞 BV-2 细胞系研究 ICA 的抗神经炎症作用及其作用机制。结果表明，ICA 抑制脂多糖 (LPS) 诱导的小胶质细胞促炎因子的产生。此外，Nrf2 信号通路的激活参与了 ICA 介导的抗神经炎症，这可以从以下观察结果中得到证明。首先，Nrf2 siRNA 逆转了 ICA 减少的小胶质细胞激活和促炎因子释放。其次，HO-1 的选择性抑制剂消除了 ICA 介导的抗神经炎症作用。本研究将使我们深入了解 Nrf2 和神经炎症在神经退行性疾病治疗方面的潜力，为其提供一种新的治疗策略。
