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柠檬桉鞣花单宁对大鼠乙醇诱导型胃溃疡的保护作用:对氧化应激、炎症及降钙素基因相关肽的影响

Protective role of ellagitannins from Eucalyptus citriodora against ethanol-induced gastric ulcer in rats: impact on oxidative stress, inflammation and calcitonin-gene related peptide.

作者信息

Al-Sayed Eman, El-Naga Reem N

机构信息

Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, 11566 Cairo, Egypt.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, 11566 Cairo, Egypt.

出版信息

Phytomedicine. 2015 Jan 15;22(1):5-15. doi: 10.1016/j.phymed.2014.10.002. Epub 2014 Oct 24.

DOI:10.1016/j.phymed.2014.10.002
PMID:25636864
Abstract

The gastroprotective activity of an ellagitannin-rich fraction obtained from Eucalyptus citriodora (ECF) was investigated against ethanol-induced gastric ulceration in rats. The rats were pretreated with ECF (25, 50 and 100mg/kg) 1h before the administration of absolute ethanol to induce acute gastric ulceration. The gastric lesions were significantly reduced by all doses of ECF. Notably, pre-treatment with ECF (100mg/kg) conferred 99.6% gastroprotection, which is significantly higher than that produced by omeprazole. Moreover, ECF administration markedly increased the mucin content in a dose-dependent manner. The potent gastroprotective effect of ECF could be partly mediated by attenuating ethanol-induced oxidative stress. ECF-pre-treatment markedly increased the depleted GSH and SOD levels in a dose-dependent manner. Moreover, ECF significantly decreased the elevated MDA tissue levels induced by ethanol administration. The results demonstrated that ECF administration exerted a powerful anti-inflammatory activity as evidenced by the reduction in the pro-inflammatory markers; IL-1β, TNF-α, 5-LO and COX-2. Additionally, the caspase-3 tissue levels were significantly reduced in the groups pre-treated with ECF. These results suggest that ECF could exert a beneficial gastroprotective effect through their antioxidant, anti-inflammatory and anti-apoptotic properties. Furthermore, ECF pre-treatment significantly attenuated the ethanol-induced decrease in CGRP expression, which has a protective role against gastric ulceration. Histopathological examination revealed intact mucosal layer, absence of hemorrhage and necrosis in groups treated with ECF. Ellagitannins were identified as the major active constituents responsible for the marked antioxidant and gastroprotective properties of ECF. The HPLC-PDA-ESI/MS/MS technique was employed to identify the ellagitannins of E. citriodora.

摘要

研究了从柠檬桉中提取的富含鞣花单宁的组分(ECF)对大鼠乙醇诱导的胃溃疡的胃保护活性。在给予无水乙醇诱导急性胃溃疡前1小时,用ECF(25、50和100mg/kg)对大鼠进行预处理。所有剂量的ECF均能显著减少胃损伤。值得注意的是,用ECF(100mg/kg)预处理可提供99.6%的胃保护作用,显著高于奥美拉唑产生的保护作用。此外,给予ECF能以剂量依赖的方式显著增加黏液含量。ECF的强大胃保护作用可能部分是通过减轻乙醇诱导的氧化应激来介导的。ECF预处理能以剂量依赖的方式显著增加耗尽的谷胱甘肽(GSH)和超氧化物歧化酶(SOD)水平。此外,ECF显著降低了乙醇给药诱导的升高的丙二醛(MDA)组织水平。结果表明,给予ECF具有强大的抗炎活性,这可通过促炎标志物白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、5-脂氧合酶(5-LO)和环氧化酶-2(COX-2)的减少来证明。此外,在ECF预处理组中,半胱天冬酶-3组织水平显著降低。这些结果表明,ECF可通过其抗氧化、抗炎和抗凋亡特性发挥有益的胃保护作用。此外,ECF预处理显著减轻了乙醇诱导的降钙素基因相关肽(CGRP)表达的降低,CGRP对胃溃疡具有保护作用。组织病理学检查显示,用ECF处理的组黏膜层完整,无出血和坏死。鞣花单宁被确定为负责ECF显著抗氧化和胃保护特性的主要活性成分。采用高效液相色谱-光电二极管阵列-电喷雾串联质谱(HPLC-PDA-ESI/MS/MS)技术鉴定了柠檬桉中的鞣花单宁。

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