Ellagitannins from Rubus Berries for the Control of Gastric Inflammation: In Vitro and In Vivo Studies

Ellagitannins have shown anti-inflammatory and anti-Helicobacter pylori properties; however, their anti-inflammatory activity at gastric level was not previously investigated. The aim of this research was to evaluate the effects of ellagitannins from Rubus berries on gastric inflammation. Ellagitannin enriched extracts (ETs) were prepared from Rubus fruticosus L. (blackberry) and Rubus idaeus L. (raspberry). The anti-inflammatory activity was tested on gastric cell line AGS stimulated by TNF-α and IL-1β for evaluating the effect on NF-kB driven transcription, nuclear translocation and IL-8 secretion. In vivo the protective effect of ellagitannins was evaluated in a rat model of ethanol-induced gastric lesions. Rats were treated orally for ten days with 20 mg/kg/day of ETs, and ethanol was given one hour before the sacrifice. Gastric mucosa was isolated and used for the determination of IL-8 release, NF-kB nuclear translocation, Trolox equivalents, superoxide dismutase and catalase activities. In vitro, ETs inhibited TNF-α induced NF-kB driven transcription (IC₅₀: 0.67-1.73 µg/mL) and reduced TNF-α-induced NF-kB nuclear translocation (57%-67% at 2 µg/mL). ETs inhibited IL-8 secretion induced by TNF-α and IL-1β at low concentrations (IC₅₀ range of 0.7-4 µg/mL). Sanguiin H-6 and lambertianin C, the major ETs present in the extracts, were found to be responsible, at least in part, for the effect of the mixtures. ETs of blackberry and raspberry decreased Ulcer Index by 88% and 75% respectively and protected from the ethanol induced oxidative stress in rats. CINC-1 (the rat homologue of IL-8) secretion in the gastric mucosa was reduced in the animals receiving blackberry and raspberry ETs. The effect of ETs on CINC-1 was associated to a decrease of NF-κB nuclear translocation in ETs treated animals. The results of the present study report for the first time the preventing effect of ETs in gastric inflammation and support for their use in dietary regimens against peptic ulcer.

鞣花丹宁具有抗炎和抗幽门螺杆菌的特性;然而，他们在胃水平的抗炎活性以前没有被调查。本研究旨在评价悬钩子花鞣花鞣质对胃炎的治疗作用。以黑莓(blackberry)和树莓(Rubus idaeus L.)为原料，制备了富含鞣花丹宁的提取物(ETs)。以TNF-α和IL-1β刺激的胃细胞系AGS，检测其抗炎活性，评价其对NF-kB驱动的转录、核转位和IL-8分泌的影响。用大鼠乙醇胃损伤模型评价鞣花丹宁的体内保护作用。大鼠灌胃10 d，灌胃ETs 20 mg/kg/d，处死前1 h灌胃乙醇。分离胃黏膜，测定IL-8释放、NF-kB核转位、Trolox当量、超氧化物歧化酶、过氧化氢酶活性。体外，ETs抑制TNF-α诱导的NF-kB驱动转录(IC₅₀:0.67-1.73µg/mL)，并减少TNF-α诱导的NF-kB核易位(在2µg/mL时57%-67%)。ETs在低浓度下抑制TNF-α和IL-1β诱导的IL-8分泌(IC₅₀range of 0.7-4µg/mL)。研究发现，在提取物中存在的主要ETs Sanguiin H-6和朗伯田宁C至少是混合物效果的部分原因。黑莓和覆盆子提取物对大鼠乙醇诱导的氧化应激有一定的保护作用，使大鼠溃疡指数分别降低88%和75%。在接受黑莓和覆盆子et的动物胃粘膜中，ccin -1(大鼠IL-8同源物)分泌减少。ETs对cin -1的影响与ETs处理动物NF-κB核易位的降低有关。本研究的结果首次报道了ETs在胃炎症中的预防作用，并支持其在抗消化性溃疡的饮食方案中使用。

Read More

http://med.wanfangdata.com.cn/Paper/Detail/PeriodicalPaper_PM23940786