Park Sun Young, Kim Young Hun, Park Geuntae
Bio-IT Fusion Technology Research Institute, Pusan National University, Busan, Korea.
Bio-IT Fusion Technology Research Institute, Pusan National University, Busan, Korea; Department of Nanomaterials Engineering, Pusan National University, Busan, Korea.
Chin J Nat Med. 2016 May;14(5):343-53. doi: 10.3724/SP.J.1009.2016.00343.
Excessive microglial cell activation is related to the progression of chronic neuro-inflammatory disorders. Heme oxygenase-1 (HO-1) expression mediated by the NFE2-related factor (Nrf-2) pathway is a key regulator of neuro-inflammation. Nardostachys chinensis is used as an anti-malarial, anti-nociceptive, and neurotrophic treatment in traditional Asian medicines. In the present study, we examined the effects of an ethyl acetate extract of N. chinensis (EN) on the anti-neuro-inflammatory effects mediated by HO-1 up-regulation in Salmonella lipopolysaccharide (LPS)- or Staphylococcus aureus lipoteichoic acid (LTA)-stimulated BV2 microglial cells. Our results indicated that EN suppressed pro-inflammatory cytokine production and induced HO-1 transcription and translation through Nrf-2/antioxidant response element (ARE) signaling. EN markedly inhibited LPS- and LTA-induced activation of nuclear factor-kappa B (NF-κB) as well as phosphorylation of mitogen-activated protein kinases (MAPKs) and signal transducer and activator of transcription (STAT). Furthermore, EN protected hippocampal HT22 cells from indirect neuronal toxicity mediated by LPS- and LTA-treated microglial cells. These results suggested that EN impairs LPS- and LTA-induced neuro-inflammatory responses in microglial cells and confers protection against indirect neuronal damage to HT22 cells. In conclusion, our findings indicate that EN could be used as a natural anti-neuro-inflammatory and neuroprotective agent.
小胶质细胞过度激活与慢性神经炎症性疾病的进展有关。由NFE2相关因子（Nrf-2）途径介导的血红素加氧酶-1（HO-1）表达是神经炎症的关键调节因子。甘松在传统亚洲药物中用作抗疟疾、抗伤害感受和神经营养治疗药物。在本研究中，我们检测了甘松乙酸乙酯提取物（EN）对沙门氏菌脂多糖（LPS）或金黄色葡萄球菌脂磷壁酸（LTA）刺激的BV2小胶质细胞中HO-1上调介导的抗神经炎症作用的影响。我们的结果表明，EN通过Nrf-2/抗氧化反应元件（ARE）信号传导抑制促炎细胞因子的产生，并诱导HO-1的转录和翻译。EN显著抑制LPS和LTA诱导的核因子κB（NF-κB）激活以及丝裂原活化蛋白激酶（MAPK）和信号转导及转录激活因子（STAT）的磷酸化。此外，EN保护海马HT22细胞免受LPS和LTA处理的小胶质细胞介导的间接神经元毒性。这些结果表明，EN可减轻LPS和LTA诱导的小胶质细胞神经炎症反应，并对HT22细胞的间接神经元损伤具有保护作用。总之，我们的研究结果表明，EN可作为一种天然的抗神经炎症和神经保护剂。
