Licochalcone A activates Nrf2 in vitro and contributes to licorice extract-induced lowered cutaneous oxidative stress in vivo

Licochalcone A activates Nrf2 in vitro and contributes to licorice extract-induced lowered cutaneous oxidative stress in vivo
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DOI:
10.1111/exd.12588
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发表时间:
2015-01-01
影响因子:
3.6
通讯作者:
Neufang, Gitta
Neufang, Gitta
中科院分区:
医学2区
文献类型:
--
作者:
Kuehnl, Jochen;Roggenkamp, Dennis;Neufang, Gitta

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逆查耳酮甘草查耳酮A(LicA)先前已被证明具有抗菌和抗炎特性。在这项研究中,我们专注于负责LicA的抗氧化特性的途径。在体外,LicA通过激活细胞保护性II相酶的表达,保护免受活性氧(ROS)介导的氧化应激。LicA诱导原代人成纤维细胞中NF-E2相关因子2(Nrf 2)的核转位,并提高细胞保护和抗炎酶血红素加氧酶1和谷氨酸-半胱氨酸连接酶修饰亚基的表达。在UVA照射的人皮肤成纤维细胞以及活化的中性粒细胞中,LicA处理的细胞显示出更高的还原型谷胱甘肽与氧化型谷胱甘肽的比率和降低的ROS浓度。在体内,用富含LicA的甘草提取物处理的皮肤的超弱光子发射分析揭示了显著降低的UVA诱导的发光,表明氧化过程减少。我们从这些数据中得出结论,甘草提取物的局部应用是一种很有前途的方法,以诱导Nrf 2依赖的细胞保护在人类皮肤。
The retrochalcone licochalcone A (LicA) has previously been shown to possess antimicrobial and anti-inflammatory properties. In this study, we focused on pathways responsible for the antioxidative properties of LicA. In vitro, LicA protected from oxidative stress mediated by reactive oxygen species (ROS) by activating the expression of cytoprotective phase II enzymes. LicA induced nuclear translocation of NF-E2-related factor 2 (Nrf2) in primary human fibroblasts and elevated the expression of the cytoprotective and anti-inflammatory enzymes heme oxygenase 1 and glutamate-cysteine ligase modifier subunit. LicA-treated cells displayed a higher ratio of reduced to oxidized glutathione and decreased concentrations of ROS in UVA-irradiated human dermal fibroblasts, as well as in activated neutrophils. In vivo, ultraweak photon emission analysis of skin treated with LicA-rich licorice extract revealed a significantly lowered UVA-induced luminescence, indicative for a decrease in oxidative processes. We conclude from these data that topical application of licorice extract is a promising approach to induce Nrf2-dependent cytoprotection in human skin.