Mangiferin Mitigates Gastric Ulcer in Ischemia/ Reperfused Rats: Involvement of PPAR-γ, NF-κB and Nrf2/HO-1 Signaling Pathways.
Mangiferin Mitigates Gastric Ulcer in Ischemia/ Reperfused Rats: Involvement of PPAR-γ, NF-κB and Nrf2/HO-1 Signaling Pathways.
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DOI：
10.1371/journal.pone.0132497
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
El-Abhar HS
中科院分区：
文献类型：
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作者：
Mahmoud-Awny M;Attia AS;Abd-Ellah MF;El-Abhar HS
芒果苷（Mangiferin，MF）是芒果中的一种黄酮类化合物，具有抗分泌和抗氧化的胃保护作用，但其分子机制尚未阐明。因此，本研究的目的是首次使用缺血/再灌注模型测试其对几个信号通路的调节作用。动物接受MF、奥美拉唑（OMP）和溶剂给药。MF可能通过诱导Nrf 2、HO-1和PPAR-γ的表达沿着下调NF-κB的表达而发挥胃保护作用。令人惊讶的是，MF的作用，特别是高剂量，超过了OMP介导的作用，除了Nrf 2。分子结果反映在测量的生物标志物上，其中MF的抗氧化作用通过增加总抗氧化能力和谷胱甘肽来表现，除了使丙二醛水平正常化之外。此外，MF降低I/R诱导的一氧化氮升高，效果优于OMP。在血清中，MF，剂量依赖性，增强内皮型一氧化氮合酶，而减少诱导亚型。关于MF的抗炎作用，它降低了IL-1β和sE-选择素的血清水平，这种作用反映在髓过氧化物酶（中性粒细胞浸润标志物）的组织水平上。此外，MF还具有抗凋亡作用，其作用机制为升高Bcl-2水平，降低caspase-3水平，并呈剂量相关性。结论：MF的胃保护作用可能通过调节Nrf 2/HO-1、PPAR-γ/NF-κB信号通路介导氧化应激、炎症反应和细胞凋亡。
Mangiferin (MF), a xanthonoid from Mangifera indica, has been proved to have antisecretory and antioxidant gastroprotective effects against different gastric ulcer models; however, its molecular mechanism has not been previously elucidated. Therefore, the aim of this study was to test its modulatory effect on several signaling pathways using the ischemia/reperfusion model for the first time. Animals were treated with MF, omeprazole (OMP), and the vehicle. The mechanistic studies revealed that MF mediated its gastroprotective effect partly via inducing the expression of Nrf2, HO-1 and PPAR-γ along with downregulating that of NF-κB. Surprisingly, the effect of MF, especially the high dose, exceeded that mediated by OMP except for Nrf2. The molecular results were reflected on the biomarkers measured, where the antioxidant effect of MF was manifested by increasing total antioxidant capacity and glutathione, besides normalizing malondialdehyde level. Additionally, MF decreased the I/R-induced nitric oxide elevation, an effect that was better than that of OMP. In the serum, MF, dose dependently, enhanced endothelial nitric oxide synthase, while reduced the inducible isoform. Regarding the anti-inflammatory effect of MF, it reduced serum level of IL-1β and sE-selectin, effects that were mirrored on the tissue level of myeloperoxidase, the neutrophil infiltration marker. In addition, MF possessed an antiapoptotic character evidenced by elevating Bcl-2 level and reducing that of caspase-3 in a dose related order. As a conclusion, the intimated gastroprotective mechanisms of MF are mediated, partially, by modulation of oxidative stress, inflammation and apoptosis possibly via the Nrf2/HO-1, PPAR-γ/NF-κB signaling pathways.