Antioxidant Opuntia ficus-indica Extract Activates AHR-NRF2 Signaling and Upregulates Filaggrin and Loricrin Expression in Human Keratinocytes
Antioxidant Opuntia ficus-indica Extract Activates AHR-NRF2 Signaling and Upregulates Filaggrin and Loricrin Expression in Human Keratinocytes
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DOI：
10.1089/jmf.2014.3396
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发表时间：
2015-10-01
影响因子：
2.4
通讯作者：
Furue, Masutaka
中科院分区：
文献类型：
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作者：
Nakahara, Takeshi;Mitoma, Chikage;Furue, Masutaka
仙人掌（Opuntia ficus-indica，OFI）是一种仙人掌属植物，被广泛用作抗炎、抗血脂和降血糖剂。研究表明，OFI提取物（OFIE）可抑制糖尿病和肝病动物模型中的氧化应激;然而，其抗氧化机制在很大程度上仍然未知。在这项研究中，我们证明OFIE通过激活核因子红细胞2相关因子2（NRF 2）和下游抗氧化酶NAD（P）H：醌氧化还原酶1（NQO 1），抑制肿瘤坏死因子或苯并芘刺激的角质形成细胞中活性氧的产生，表现出有效的抗氧化活性。OFIE的抗氧化能力在NRF 2敲低的角质形成细胞中被取消。OFIE通过激活芳烃受体（AHR）发挥这种NRF 2-NQO 1上调作用。此外，通过OFIE连接AHR上调了表皮屏障蛋白：聚丝蛋白和兜甲蛋白的表达。OFIE还以AHR依赖性方式阻止TH 2丝氨酸介导的聚丝蛋白和兜甲蛋白表达的下调，因为它在AHR敲低的角质形成细胞中被取消。抗氧化剂OFIE是AHR-NRF 2-NQO 1信号传导的有效激活剂，并且可能有益于治疗屏障破坏的皮肤疾病。
Opuntia ficus-indica (OFI) is a cactus species widely used as an anti-inflammatory, antilipidemic, and hypoglycemic agent. It has been shown that OFI extract (OFIE) inhibits oxidative stress in animal models of diabetes and hepatic disease; however, its antioxidant mechanism remains largely unknown. In this study, we demonstrated that OFIE exhibited potent antioxidant activity through the activation of nuclear factor erythroid 2-related factor 2 (NRF2) and the downstream antioxidant enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1), which inhibited the generation of reactive oxygen species in keratinocytes challenged with tumor necrosis factor or benzo[]pyrene. The antioxidant capacity of OFIE was canceled in NRF2 knockdown keratinocytes. OFIE exerted this NRF2-NQO1 upregulation through activation of the aryl hydrocarbon receptor (AHR). Moreover, the ligation of AHR by OFIE upregulated the expression of epidermal barrier proteins: filaggrin and loricrin. OFIE also prevented TH2 cytokine-mediated downregulation of filaggrin and loricrin expression in an AHR-dependent manner because it was canceled in AHR knockdown keratinocytes. Antioxidant OFIE is a potent activator of AHR-NRF2-NQO1 signaling and may be beneficial in treating barrier-disrupted skin disorders.