Structural characterization and protective effects of a glucuronogalactomannan from Tetrastigma hemsleyanum against diabetic retinopathy via targeting ferroptosis pathway

IF 10.7 1区化学 Q1 CHEMISTRY, APPLIED

Carbohydrate Polymers Pub Date : 2025-07-12 DOI:10.1016/j.carbpol.2025.124059

Jie Zhou , Xiyu Mei , Lianghui Zhan , Xia Liu , Bin Wang , Baisheng Xu , Xuechun Jiang

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Abstract

A novel polysaccharide, THPE2-F, with an average molecular weight of 480.75 kDa, was isolated and characterized from the roots of Tetrastigma hemsleyanum Diels et Gilg. Extensive structural analyses revealed that THPE2-F is a GlcA-Gal-Man polymer. Its main chain is composed of →4)-β-D-GlcpA-(1→ and →2)-α-D-Manp-(1→ linkages. THPE2-F mainly consists of galactose, mannose, and glucuronic acid residues. The glycosidic linkages of THPE2-F were elucidated via methylation analysis and further corroborated by nuclear magnetic resonance (NMR) spectroscopy. In vitro, THPE2-F significantly decreased the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), and enhanced cell viability at a concentration of 100 μg/mL. Additionally, treatment with THPE2-F downregulated the expression of NCOA4, thereby uncovering a molecular mechanism responsible for its protective effects. Biochemical analyses indicated that THPE2-F restored glutathione (GSH) levels under hyperglycemic conditions and regulated iron levels, subsequently affecting the expression of ferroptosis-related proteins, including COX2, NOX1, FACL4 and NCOA4. In vivo studies further validated these findings, as THPE2-F provided substantial protection against retinal damage in a diabetic retinopathy (DR) mouse model. Collectively, these results suggest that THPE2-F has potential as a therapeutic agent for diabetic retinopathy by targeting ferroptosis pathways.

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hemsleyantetrastigma葡糖醛酸半乳甘露聚糖的结构表征及通过铁下垂途径对糖尿病视网膜病变的保护作用

从赤藓（Tetrastigma hemsleyanum Diels et Gilg）根中分离得到一种平均分子量为480.75 kDa的新多糖THPE2-F。广泛的结构分析表明THPE2-F是一种GlcA-Gal-Man聚合物。其主链由→4)-β- d - glcpa -(1→和→2)-α- d - manp -(1→键组成。THPE2-F主要由半乳糖、甘露糖和葡萄糖醛酸残基组成。通过甲基化分析确定了THPE2-F的糖苷键，并通过核磁共振（NMR）谱进一步证实。在体外，100 μg/mL浓度的THPE2-F显著降低丙二醛（MDA）和活性氧（ROS）水平，增强细胞活力。此外，用THPE2-F处理可下调NCOA4的表达，从而揭示了其保护作用的分子机制。生化分析表明，THPE2-F可恢复高血糖状态下的谷胱甘肽（GSH）水平，调节铁水平，进而影响铁中毒相关蛋白的表达，包括COX2、NOX1、FACL4和NCOA4。体内研究进一步验证了这些发现，因为THPE2-F在糖尿病视网膜病变（DR）小鼠模型中提供了实质性的视网膜损伤保护。总的来说，这些结果表明THPE2-F有潜力通过靶向铁下垂途径作为糖尿病视网膜病变的治疗剂。

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来源期刊

Carbohydrate Polymers 化学-高分子科学

CiteScore

22.40

自引率

8.00%

发文量

1286

审稿时长

47 days

期刊介绍： Carbohydrate Polymers stands as a prominent journal in the glycoscience field, dedicated to exploring and harnessing the potential of polysaccharides with applications spanning bioenergy, bioplastics, biomaterials, biorefining, chemistry, drug delivery, food, health, nanotechnology, packaging, paper, pharmaceuticals, medicine, oil recovery, textiles, tissue engineering, wood, and various aspects of glycoscience. The journal emphasizes the central role of well-characterized carbohydrate polymers, highlighting their significance as the primary focus rather than a peripheral topic. Each paper must prominently feature at least one named carbohydrate polymer, evident in both citation and title, with a commitment to innovative research that advances scientific knowledge.