18β-Glycyrrhetinic acid mitigates radiation-induced skin damage via NADPH oxidase/ROS/p38MAPK and NF-κB pathways
18β-Glycyrrhetinic acid mitigates radiation-induced skin damage via NADPH oxidase/ROS/p38MAPK and NF-κB pathways
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DOI：
10.1016/j.etap.2018.04.012
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发表时间：
2018-06-01
影响因子：
4.3
通讯作者：
Hong, Jinsheng
中科院分区：
文献类型：
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作者：
Su, Li;Wang, Zeng;Hong, Jinsheng
放射性炎症在放射性组织损伤中起重要作用。18 β-甘草次酸（18 β-GA）具有抗炎活性。本研究旨在评估18 β-GA对辐射诱导的皮肤损伤的活性，并探讨其潜在的机制。体外实验显示18 β-GA处理降低了照射后的RAW 264.7巨噬细胞中IL-1 β、IL-6、PGE 2的产生，并降低了p38 MAPK磷酸化、AP-1的DNA结合活性和NF-κ B B活化。此外，18 β-GA通过抑制NF-κ B/p65和I κ B-α磷酸化来抑制NF-κ B B活化，并减轻经辐照的RAW 264.7巨噬细胞中ROS的过度产生。体内实验显示18 β-GA可减轻放射性皮肤损伤的严重程度，减少皮肤组织中的炎性细胞浸润和TNF-α、IL-1 β和IL-6水平。我们的研究结果表明，18 β-GA对辐射诱导的皮肤损伤表现出抗炎作用，可能是通过抑制NADPH氧化酶活性、ROS产生、p38 MAPK和NF-κ B信号的激活以及NF-κ B和AP-1的DNA结合活性，从而抑制促炎细胞因子的产生。
Radiation-induced inflammation plays an important role in radiation-induced tissue injury. 18 beta-glycyrrhetinic acid (18 beta-GA) has shown an anti-inflammatory activity. This study aimed to assess the activity of 18 beta-GA against radiation-induced skin damage, and explore the underlying mechanisms. In vitro assay revealed 18 beta-GA treatment decreased the production of IL-1 beta, IL-6, PGE2 and decreased p38MAPK phosphorylation, DNA-binding activity of AP-1, and NF-kappa B activation in irradiated RAW264.7 macrophages. Additionally, 18 beta-GA suppressed NF-kappa B activation by inhibiting NF-kappa B/p65 and I kappa B-alpha phosphorylation and alleviated ROS overproduction in irradiated RAW264.7 macrophages. In vivo assay showed 18 beta-GA alleviated severity of radiation-induced skin damage, reduced inflammatory cell infiltration and TNF-alpha, IL-1 beta and IL-6 levels in cutaneous tissues. Our findings demonstrate that 18 beta-GA exhibits anti-inflammatory actions against radiation-induced skin damage probably by inhibiting NADPH oxidase activity, ROS production, activation of p38MAPK and NF-kappa B signaling, and the DNA binding activities of NF-kappa B and AP-1, consequently suppressing pro-inflammatory cytokine production.