Prenylated xanthones from mangosteen (Garcinia mangostana) activate the AhR and Nrf2 pathways and protect intestinal barrier integrity in HT-29 cells.
Prenylated xanthones from mangosteen (Garcinia mangostana) activate the AhR and Nrf2 pathways and protect intestinal barrier integrity in HT-29 cells.
复制标题
从Mangosteen（Garcinia Mangostana）中的原酰化的黄色thone激活了AHR和NRF2途径，并保护HT-29细胞中的肠道屏障完整性。
DOI：
10.1016/j.freeradbiomed.2020.11.018
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发表时间：
2021-02-01
影响因子：
7.4
通讯作者：
Johnson JJ
中科院分区：
文献类型：
--
作者：
Tocmo R;Le B;Heun A;van Pijkeren JP;Parkin K;Johnson JJ
热带水果山竹中的氧杂蒽酮具有抗炎和抗氧化活性。在这里，我们分离并确定潜在的诱导剂的芳烃受体（AhR）和核因子红细胞2相关因子2（Nrf 2）信号通路从山竹使用生物测定指导的战略。对山竹果果皮提取物进行连续的溶剂提取，然后进行色谱法结合NMR光谱和质谱分析，以鉴定和分离纯化合物。活性级分的分离导致七个异戊烯基氧杂蒽酮，其被鉴定并随后评价生物活性。使用H1L6.1c3（AhR诱导）和HepG 2-ARE（Nrf 2诱导）的体外荧光素酶报告细胞测定用于鉴定AhR和Nrf 2激活剂。所有七个异戊二烯化的氧杂蒽酮显示AhR诱导活性，而只有五个氧杂蒽酮激活Nrf 2。Garcinone D（GarD）可显著上调HT-29细胞AhR/Cyp 1a 1和Nrf 2/HO-1蛋白表达，并增强闭合小带-1和occludin蛋白水平。此外，GarD通过增强紧密连接（TJ）蛋白和抑制活性氧的产生来抑制氧化应激诱导的肠上皮屏障功能障碍。通过用AhR拮抗剂预处理细胞来抑制AhR揭示了AhR途径是GarD改善上皮屏障功能所必需的。这些结果强调了GarD的双重机制，该机制赋予对肠上皮屏障功能障碍的保护。
Xanthones from the tropical fruit mangosteen (Garcinia mangostana) display anti-inflammatory and anti-oxidative activities. Here, we isolate and identify potential inducers of the aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways from mangosteen using a bioassay-guided strategy. Mangosteen fruit pericarp extracts were subjected to sequential solvent extractions, followed by chromatography coupled with NMR spectroscopy and mass spectrometric analyses for identification and isolation of pure compounds. Isolation of active fractions led to seven prenylated xanthones that were identified and subsequently evaluated for bioactivity. In vitro luciferase reporter cellular assays using H1L6.1c3 (AhR induction) and HepG2-ARE (Nrf2 induction) were used to identify AhR and Nrf2 activators. All seven prenylated xanthones displayed AhR inducing activity, whereas only five xanthones activated Nrf2. Garcinone D (GarD) significantly upregulated AhR/Cyp1a1 and Nrf2/HO-1 protein expression and enhanced zonula occludens-1 and occludin protein levels in HT-29 cells. In addition, GarD inhibited oxidative stress-induced intestinal epithelial barrier dysfunction by enhancing tight junction (TJ) proteins and inhibition of reactive oxygen species production. Inhibition of AhR by pretreating cells with an AhR antagonist revealed that the AhR pathway is required for the improved epithelial barrier functions of GarD. These results highlight a dual mechanism by GarD that confers protection against intestinal epithelial barrier dysfunction.
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影响因子：
29.4
作者：
Dahan S;Rabinowitz KM;Martin AP;Berin MC;Unkeless JC;Mayer L
通讯作者：
Mayer L
影响因子：
5.1
作者：
BENNETT, GJ;LEE, HH;LEE, LP
通讯作者：
LEE, LP
影响因子：
5.2
作者：
Bumrungpert, Akkarach;Kalpravidh, Ruchaneekorn W.;Failla, Mark L.
通讯作者：
Failla, Mark L.
影响因子：
--
作者：
Aisha AF;Abu-Salah KM;Ismail Z;Majid AM
通讯作者：
Majid AM
影响因子：
5.2
作者：
Gutierrez-Orozco, Fabiola;Thomas-Ahner, Jennifer M.;Berman-Booty, Lisa D.;Galley, Jeffrey D.;Chitchumroonchokchai, Chureeporn;Mace, Thomas;Suksamrarn, Sunit;Bailey, Michael T.;Clinton, Steven K.;Lesinski, Gregory B.;Failla, Mark L.
通讯作者：
Failla, Mark L.