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Capillarisin augments anti-oxidative and anti-inflammatory responses by activating Nrf2/HO-1 signaling

机译:Capillarisin通过激活NRF2 / HO-1信号来增加抗氧化和抗炎反应

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Capillarisin is a naturally isolated chromone, which is one of the major bioactive constituents of Artemisia capillaries. Capillarisin has antioxidant, anti-inflammatory, and anti-tumor potential, but the underlying molecular mechanisms remain largely unclear. In the present study, we demonstrate that the transcription factor nuclear factor E2-related factor-2 (Nrf2) is activated by capillarisin in neuroblastoma SH-SY5Y cells and microglial BV2 cells. Capillarisin leads to Nrf2 phosphorylation, subsequent activation of antioxidant response element (ARE)-mediated transcription, and up-regulation of downstream molecules, such as heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1. Capillarisin protects SH-SY5Y cells froth 6-hydroxydopamine-induced oxidative stress and attenuates inflammatory responses in lipopolysaccharide-treated BV2 cells. The cytoprotective and anti-inflammatory effects of capillarisin are significantly abolished in cells transfected with specific Nrf2 or HO-1 siRNA, suggesting that these pharmacological properties of capillarisin are primarily due to increased HO-1 activity. Capillarisin induces the activation of c-Jun N-terminal kinase in SH-SY5Y and BV2 cells, which is responsible for Nrf2 phosphorylation and HO-1 upregulation. Together, this study demonstrates that capillarisin is a potential activator of the Nrf2/ARE-dependent pathway and could be an attractive candidate for the regulation of oxidative stress and inflammatory responses in the brain. (C) 2017 Elsevier Ltd. All rights reserved.
机译:Capillarisin是一种天然分离的铬酮,是蒿甲毛细血管的主要生物活性成分之一。毛细血管具有抗氧化剂,抗炎和抗肿瘤潜力,但下面的分子机制仍然很大程度上不清楚。在本研究中,我们证明转录因子核因子E2相关因子-2(NRF2)通过辣椒素SH-SEC5Y细胞和微胶质组织BV2细胞激活Capillarisin。毛细血管导致NRF2磷酸化,随后激活抗氧化剂响应元件(是)介导的转录,以及下游分子的上下调,如血红素氧合酶-1(HO-1)和NAD(P)H:醌氧化还原酶1.辣椒素保护SH-SY5Y细胞泡沫泡沫泡沫诱导的氧化应激并衰减脂多糖处理的BV2细胞中的炎症反应。用特异性NRF2或HO-1 siRNA转染细胞的细胞保护和抗炎作用显着消除,表明这些辣椒素的这些药理学性质主要是由于HO-1活性增加。辣椒素诱导SH-SY5Y和BV2细胞中C-JUM N-末端激酶的活化,这对NRF2磷酸化和HO-1上调负责。该研究在一起表明毛细血管是NRF2 /依赖性途径的潜在激活剂,并且可以是用于调节氧化应激和脑中炎症反应的有吸引力的候选者。 (c)2017 Elsevier Ltd.保留所有权利。

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