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白及寡糖通过激活NF-κB信号通路和调节肠道微生物群改善5-氟尿嘧啶诱导的小鼠肠道黏膜炎。

Bletilla oligosaccharides improved 5-fluorouracil-induced intestinal mucositis in mice by activating NF-κB signalling pathway and regulating intestinal microbiota.

作者信息

Yin Qiuxiong, Li Xinran, Xiong Yanli, Jiang Yupeng, Ma Shengsuo, Qian Guoqiang

机构信息

School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China.

Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China.

出版信息

Front Pharmacol. 2025 Mar 13;16:1526274. doi: 10.3389/fphar.2025.1526274. eCollection 2025.

Abstract

INTRODUCTION

The Bletilla oligosaccharides (BO) are active compounds extracted from and have the strong protective effect on the gastrointestinal tract. Chemotherapeutic intestinal mucositis (CIM) is one of the toxic side effects of chemotherapeutic agents on the gastrointestinal tract. The aim of this study was to identify the structure of BO and evaluate the therapeutic effect of BO on 5-fluorouracil-induced intestinal mucosal inflammation.

METHODS

BO were purified from DEAE52 cellulose. The structure of BO were characterised by HPGPC, GC-MS and NMR. , the mouse model of intestinal mucositis was established by intraperitoneal injection of 5-FU. The effect of BO on intestinal mucositis in mice was detected by assessing the levels of intestinal flora, ZO-1, occludin, and MUC-2, and inflammatory cytokines (IL-1β, IL-6, IL-10, and TNF-α).

RESULTS

Structural characterisation showed that BO were the neutral polysaccharide composed mainly of glucose and mannose. The backbone of BO consisted of→4)-β-Manp-(1→, →4)-β-Glcp-(1→ and small →3,4)-α-Manp-(1→. The results of the experiment showed that the symptoms of diarrhoea, haematochezia and colonic mucosal lesions improved after administration of BO. Further experiments showed that BO not only reduced the levels of pro-inflammatory factors such as IL-1β, IL-6 and TNF-α, but also improved the expression of intestinal barrier protein and intestinal microbial community after BO treatment.

CONCLUSION

BO can relieve the progress of intestinal mucositis by relieving inflammation, protecting the intestinal epithelial barrier and regulating the intestinal microbiota. These data provide experimental evidence for the application of BO in chemotherapeutic intestinal mucositis.

摘要

引言

白及寡糖(BO)是从白及中提取的活性化合物,对胃肠道具有强大的保护作用。化疗性肠黏膜炎(CIM)是化疗药物对胃肠道产生的毒副作用之一。本研究旨在鉴定BO的结构,并评估BO对5-氟尿嘧啶诱导的肠黏膜炎症的治疗效果。

方法

从DEAE52纤维素中纯化BO。通过高效凝胶渗透色谱法(HPGPC)、气相色谱-质谱联用仪(GC-MS)和核磁共振(NMR)对BO的结构进行表征。此外,通过腹腔注射5-氟尿嘧啶建立小鼠肠黏膜炎模型。通过评估肠道菌群、紧密连接蛋白1(ZO-1)、闭合蛋白、黏蛋白2(MUC-2)以及炎性细胞因子(白细胞介素-1β、白细胞介素-6、白细胞介素-10和肿瘤坏死因子-α)的水平,检测BO对小鼠肠黏膜炎的影响。

结果

结构表征显示BO是主要由葡萄糖和甘露糖组成的中性多糖。BO的主链由→4)-β-D-吡喃甘露糖基-(1→、→4)-β-D-吡喃葡萄糖基-(1→和少量→3,4)-α-D-吡喃甘露糖基-(1→组成。实验结果表明,给予BO后,腹泻、便血和结肠黏膜损伤等症状有所改善。进一步实验表明,BO不仅降低了白细胞介素-1β、白细胞介素-6和肿瘤坏死因子-α等促炎因子的水平,还改善了BO治疗后肠道屏障蛋白的表达和肠道微生物群落。

结论

BO可通过减轻炎症、保护肠道上皮屏障和调节肠道微生物群来缓解肠黏膜炎的进展。这些数据为BO在化疗性肠黏膜炎中的应用提供了实验依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42b8/11965902/d6ead0cb4d34/fphar-16-1526274-g001.jpg

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