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铁皮石斛多糖在体外和体内保护胃黏膜细胞免受氧化损伤诱导的凋亡。

Polysaccharides of Dendrobium officinale Kimura & Migo protect gastric mucosal cell against oxidative damage-induced apoptosis in vitro and in vivo.

作者信息

Zeng Qiang, Ko Chun-Hay, Siu Wing-Sum, Li Long-Fei, Han Xiao-Qiang, Yang Liu, Bik-San Lau Clara, Hu Jiang-Miao, Leung Ping-Chung

机构信息

Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China.

Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, Guangdong, China.

出版信息

J Ethnopharmacol. 2017 Aug 17;208:214-224. doi: 10.1016/j.jep.2017.07.006. Epub 2017 Jul 4.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Dendrobium officinale Kimura & Migo (DO) is a valuable Traditional Chinese Medicine to nourish stomach, in which polysaccharides are identified as active ingredients. However, limited scientific evidences have been reported on the gastroprotective efficacy of DO. The aim of the current study was to investigate the protective effects and underlying mechanism of polysaccharides from DO(DOP) on gastric mucosal injury.

MATERIAL AND METHODS

For in vitro study, HFE145 cells were pretreated with DOP before induction of cell apoptosis by HO. Cell apoptosis and related proteins expression were detected. In the in vivo study, absolute ethanol was administered orally to induce gastric mucosal injury in rat. The gastric mucosal injury area and histological examination were used to evaluate the effects of DOP treatment on the recovery of the gastric mucosal injury.

RESULTS

HO treatment for 6h significantly induced cell apoptosis in HFE145 cells. However, the destructive effects of HO on HFE 145 cells could be reversed by the pretreatment with DOP. The increased ROS level induced by HO for 4h was reduced after DOP pretreatment. The number of apoptotic cells in both early and late apoptosis stages decreased significantly and the nuclei morphology changes were improved with DOP pretreatment. Furthermore, DOP inhibited caspase 3 activation and PARP cleavage, downregulated Bax expression and upregulated Bcl2 expression in cell model. Further study revealed that pretreatment of DOP inhibited p -NF-κBp65/NF-κBp65 level, indicating DOP inhibited HO-mediated apoptosis via suppression of NF-κB activation. In addition, DOP treatment could ameliorate gastric mucosal injury and inhibit mucin loss induced by ethanol in animal model. DOP treatment also interfered with ethanol-induced apoptosis process by downregulating Bax/Bcl2 ratio in gastric mucosa.

CONCLUSIONS

The present study was the first one to demonstrate the gastroprotective effect of DOP through inhibiting oxidative stress-induced apoptosis. This study provided a solid evidence for the potential use of DO as a therapy or health supplement for gastric mucosal diseases.

摘要

民族药理学相关性

铁皮石斛是一种珍贵的滋养胃部的传统中药,其中多糖被确定为活性成分。然而,关于铁皮石斛胃保护功效的科学证据报道有限。本研究的目的是探讨铁皮石斛多糖(DOP)对胃黏膜损伤的保护作用及其潜在机制。

材料与方法

在体外研究中,HFE145细胞在通过HO诱导细胞凋亡之前先用DOP预处理。检测细胞凋亡及相关蛋白表达。在体内研究中,口服给予无水乙醇诱导大鼠胃黏膜损伤。用胃黏膜损伤面积和组织学检查来评估DOP治疗对胃黏膜损伤恢复的影响。

结果

HO处理6小时显著诱导HFE145细胞凋亡。然而,DOP预处理可逆转HO对HFE145细胞的破坏作用。DOP预处理后,HO诱导4小时所增加的ROS水平降低。DOP预处理使早期和晚期凋亡阶段的凋亡细胞数量显著减少,细胞核形态变化得到改善。此外,在细胞模型中,DOP抑制caspase 3激活和PARP裂解,下调Bax表达并上调Bcl2表达。进一步研究表明,DOP预处理抑制p -NF-κBp65/NF-κBp65水平,表明DOP通过抑制NF-κB激活来抑制HO介导的细胞凋亡。此外,在动物模型中,DOP治疗可改善胃黏膜损伤并抑制乙醇诱导的黏蛋白丢失。DOP治疗还通过下调胃黏膜中Bax/Bcl2比值来干扰乙醇诱导的细胞凋亡过程。

结论

本研究首次证明DOP通过抑制氧化应激诱导的细胞凋亡具有胃保护作用。该研究为铁皮石斛作为胃黏膜疾病的治疗药物或健康补充剂的潜在用途提供了确凿证据。

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