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佛手柑多糖的硫酸化和羧甲基化:理化性质及对脂多糖诱导的Caco-2细胞肠屏障损伤的保护作用

Sulfation and carboxymethylation of Citrus medica 'Fingered' polysaccharides: Physicochemical properties and protective effects against LPS-induced intestinal barrier injury in Caco-2 cells.

作者信息

Xiong Feng, Yao Hong-Liang, Wu Yong-Hua, Hu Wen-Hao, Ou Yang-Hui, Li Hou-Jin, Lan Wen-Jian

机构信息

State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong, China.

Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization Institute of Zoology, Guangdong Academy of Sciences, Guangzhou 510260, Guangdong, China.

出版信息

Int J Biol Macromol. 2025 Sep;321(Pt 1):146211. doi: 10.1016/j.ijbiomac.2025.146211. Epub 2025 Jul 21.

Abstract

It is well known that Citrus medica 'Fingered' is an important industrial crop resource. Our previous study found that Citrus medica 'Fingered' polysaccharides via hot water extraction (HWE-CP) can alleviate ulcerative colitis by enhancing intestinal barrier and regulating intestinal flora. However, the large molecular weight of HWE-CP (35.15 kDa) limits its absorption by intestinal cells, thereby restricting its protective effects on the intestinal barrier. In this study, HWE-CP was chemically modified to obtain sulfated derivatives (S-HWE-CP) and carboxymethylated derivatives (C-HWE-CP). Subsequently, we investigated the physicochemical, structural characteristics, and protective abilities of these derivatives on the intestinal barrier. The results indicated that chemical modification led to significant changes in the molecular weight, monosaccharide composition and molar ratio, proportion of HG domains, Zeta potential, and thermal stability of HWE-CP. C-HWE-CP, with a degree of substitution of 1.12, most effectively promoted Occludin protein expression and enhanced the integrity of the cell barrier. Further analysis using RNA-seq revealed that C-HWE-CP may alleviate damage to Caco-2 cells through pentose and glucuronate interconversion pathways. These findings provide a theoretical basis for the role of HWE-CP functional group derivatives of HWE-CP in preventing chronic diseases associated with the intestinal barrier and facilitating the development of related functional foods.

摘要

众所周知,佛手是一种重要的工业作物资源。我们之前的研究发现,通过热水提取得到的佛手多糖(HWE-CP)可通过增强肠道屏障和调节肠道菌群来缓解溃疡性结肠炎。然而,HWE-CP的大分子量(35.15 kDa)限制了其被肠道细胞吸收,从而限制了其对肠道屏障的保护作用。在本研究中,对HWE-CP进行化学修饰以获得硫酸化衍生物(S-HWE-CP)和羧甲基化衍生物(C-HWE-CP)。随后,我们研究了这些衍生物的物理化学性质、结构特征以及对肠道屏障的保护能力。结果表明,化学修饰导致HWE-CP的分子量、单糖组成和摩尔比、HG结构域比例、Zeta电位和热稳定性发生显著变化。取代度为1.12的C-HWE-CP最有效地促进了闭合蛋白的表达并增强了细胞屏障的完整性。使用RNA测序的进一步分析表明,C-HWE-CP可能通过戊糖和葡糖醛酸相互转化途径减轻对Caco-2细胞的损伤。这些发现为HWE-CP的官能团衍生物在预防与肠道屏障相关的慢性疾病以及促进相关功能性食品的开发中的作用提供了理论依据。

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