Ponciretin attenuates ethanol-induced gastric damage in mice by inhibiting inflammatory responses

Ponciretin attenuates ethanol-induced gastric damage in mice by inhibiting inflammatory responses
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DOI:
10.1016/j.intimp.2016.12.021
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发表时间:
2017-02-01
影响因子:
5.6
通讯作者:
Kim, Dong-Hyun
Kim, Dong-Hyun
中科院分区:
医学2区
文献类型:
--
作者:
Kang, Geum-Dan;Kim, Dong-Hyun

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背景:ponciin (PO)和isosakuranetin(或ponciretin [PT])是在柑橘属水果中发现的化合物。它们经常被用于中医治疗炎症和哮喘。因此,我们在体外和体内研究了它们的抗胃炎作用。方法:采用乙醇或脂多糖刺激KATO III细胞,观察PO和PT的抗炎作用。用无水乙醇灌胃诱导ICR小鼠胃炎。采用酶联免疫吸附法、免疫印迹法和定量聚合酶链反应法检测炎症标志物水平。结果:FT或PO可抑制乙醇或脂多糖刺激的KATO III细胞白细胞介素(IL)-8和肿瘤坏死因子(TNF)的分泌。它们还降低了核因子κ B (nf - κ B)的活化。预处理PT或PO对乙醇诱导的出血性胃炎有显著保护作用,其特征是小鼠水肿、组织糜烂和粘膜易碎。用PT或PO处理可抑制乙醇诱导的nf - κ B活化和TNF、IL-8和ifn - γ的释放。PT的保护作用大于PO,与阳性对照雷尼替丁相当。结论:PT可能通过调节CXCL4(或IL-8)的分泌和NF-kappa的激活,抑制免疫细胞(包括中性粒细胞)的浸润,从而减轻乙醇诱导的胃炎。
Background: Poncirin (PO) and isosakuranetin (or ponciretin [PT]) are compounds found in fruits of the genus Citrus. They are frequently used in traditional Chinese medicine for the treatment of inflammation and asthma. Therefore, we examined their anti-gastritis effects in vitro and in vivo.Methods: The anti-inflammatory effects of PO and PT were examined using ethanol- or LPS-stimulated KATO III cells. Gastritis was induced in ICR mice via intragastric injection of absolute ethanol. Levels of inflammatory markers were measured by enzyme-linked immunosorbent assay, immunoblotting, and quantitative polymerase chain reaction.Results: Treatment with FT or PO inhibited the secretion of interleukin (IL)-8 and tumor necrosis factor (TNF) in ethanol- or LPS-stimulated KATO III cells. They also reduced the activation of nuclear factor kappa B (NF-kappa B). Pretreatment with PT or PO significantly protected against ethanol-induced hemorrhagic gastritis, characterized by edema, tissue erosions, and mucosal friability in mice. Treatment with PT or PO suppressed ethanol-induced NF-kappa B activation and the release of TNF, IL-8, and IFN-gamma. The protective effect of PT was greater than that of PO and comparable to ranitidine, a positive control.Conclusion: PT may attenuate ethanol-induced gastritis by inhibiting the infiltration of immune cells, including neutrophils, via the regulation of CXCL4 (or IL-8) secretion and the activation NF-kappa B. (C) 2016 Elsevier B.V. All rights reserved.