Velagapudi Ravikanth, Kumar Asit, Bhatia Harsharan S, El-Bakoush Abdelmeneim, Lepiarz Izabela, Fiebich Bernd L, Olajide Olumayokun A
Department of Pharmacy, University of Huddersfield, Queensgate, Huddersfield, West Yorkshire HD1 3DH, United Kingdom.
Neurochemistry Research Laboratory, Department of Psychiatry and Psychotherapy, University of Freiburg Medical School, Hauptstrasse 5, 79104 Freiburg, Germany.
Int Immunopharmacol. 2017 Jul;48:17-29. doi: 10.1016/j.intimp.2017.04.018. Epub 2017 May 3.
Thymoquinone is an antioxidant phytochemical that has been shown to inhibit neuroinflammation. However, little is known about the potential roles of intracellular antioxidant signalling pathways in its anti-inflammatory activity. The objective of this study was to elucidate the roles played by activation of the Nrf2/ARE antioxidant mechanisms in the anti-inflammatory activity of this compound. Thymoquinone inhibited lipopolysaccharide (LPS)-induced neuroinflammation through interference with NF-κB signalling in BV2 microglia. Thymoquinone also activated Nrf2/ARE signalling by increasing nuclear localisation, DNA binding and transcriptional activity of Nrf2, as well as increasing protein levels of HO-1 and NQO1. Suppression of Nrf2 activity through siRNA or with the use of trigonelline resulted in the loss of anti-inflammatory activity by thymoquinone. Taken together, our studies show that thymoquinone inhibits NF-κB-dependent neuroinflammation in BV2 microglia, by targeting antioxidant pathway involving activation of both Nrf2/ARE. We propose that activation of Nrf2/ARE signalling pathway by thymoquinone probably results in inhibition of NF-κB-mediated neuroinflammation.
百里醌是一种抗氧化植物化学物质，已被证明可抑制神经炎症。然而，关于细胞内抗氧化信号通路在其抗炎活性中的潜在作用知之甚少。本研究的目的是阐明Nrf2/ARE抗氧化机制的激活在该化合物抗炎活性中所起的作用。百里醌通过干扰BV2小胶质细胞中的NF-κB信号传导来抑制脂多糖（LPS）诱导的神经炎症。百里醌还通过增加Nrf2的核定位、DNA结合和转录活性，以及增加HO-1和NQO1的蛋白质水平来激活Nrf2/ARE信号传导。通过siRNA或使用胡芦巴碱抑制Nrf2活性会导致百里醌失去抗炎活性。综上所述，我们的研究表明，百里醌通过靶向涉及Nrf2/ARE激活的抗氧化途径来抑制BV2小胶质细胞中NF-κB依赖性神经炎症。我们提出，百里醌激活Nrf2/ARE信号通路可能导致NF-κB介导的神经炎症受到抑制。
