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来自浒苔的具有抗糖尿病活性的硫酸化多糖:其结构特征以及对氧化应激和线粒体功能的影响

Antidiabetic-activity sulfated polysaccharide from Chaetomorpha linum: Characteristics of its structure and effects on oxidative stress and mitochondrial function.

作者信息

Qin Ling, Yang Yajing, Hao Jiejie, He Xiaoxi, Liu Shan, Chu Xiao, Mao Wenjun

机构信息

Key Laboratory of Marine Drugs of Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.

Key Laboratory of Marine Drugs of Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, China.

出版信息

Int J Biol Macromol. 2022 May 15;207:333-345. doi: 10.1016/j.ijbiomac.2022.02.129. Epub 2022 Feb 26.

DOI:10.1016/j.ijbiomac.2022.02.129
PMID:35227705
Abstract

A water-soluble polysaccharide from the green alga Chaetomorpha linum, designated CHS2, was obtained by water extraction, preparative anion-exchange and size-exclusion chromatography. Results of chemical and spectroscopic analyses showed that CHS2 was a sulfated rhamnogalactoarabinan, and its backbone was mainly constituted by 4-linked and 3,4-linked β-l-arabinopyranose with sulfate groups at C-2/C-3 of 4-linked β-l-arabinopyranose. The branching contained 4-linked, 6-linked β-d-galactopyranose and terminal rhamnose residues. Based on the inhibition of human islet amyloid polypeptide (hIAPP) aggregation and morphology change of hIAPP aggregates in in vitro tests, it was proved that CHS2 effectively inhibited the hIAPP aggregation and possessed strong antidiabetic activity. CHS2 was nearly no toxicity in NIT-1 cells and could attenuate hIAPP-induced cytotoxicity. CHS2 may significantly reduce the generation of intracellular reactive oxygen species and hIAPP aggregation-induced oxidative stress in NIT-1 cells. CHS2 was co-localized with mitochondria, and largely protected mitochondria function from hIAPP aggregation-induced damage through stabilizing mitochondrial membrane potential and enhancing the mitochondrial complex I, II or III activity and ATP level. The data demonstrated that CHS2 could have potential prospect to become an antidiabetic drug for type 2 diabetes mellitus treatment.

摘要

从绿藻亚麻藻中获得了一种水溶性多糖,命名为CHS2,通过水提取、制备型阴离子交换和尺寸排阻色谱法得到。化学和光谱分析结果表明,CHS2是一种硫酸化鼠李半乳阿拉伯聚糖,其主链主要由4-连接和3,4-连接的β-L-阿拉伯吡喃糖组成,4-连接的β-L-阿拉伯吡喃糖的C-2/C-3位带有硫酸基团。支链包含4-连接、6-连接的β-D-半乳吡喃糖和末端鼠李糖残基。基于体外试验中对人胰岛淀粉样多肽(hIAPP)聚集的抑制以及hIAPP聚集体形态的变化,证明CHS2能有效抑制hIAPP聚集并具有较强的抗糖尿病活性。CHS2在NIT-1细胞中几乎没有毒性,并且可以减轻hIAPP诱导的细胞毒性。CHS2可能显著减少NIT-1细胞内活性氧的产生以及hIAPP聚集诱导的氧化应激。CHS2与线粒体共定位,并通过稳定线粒体膜电位以及增强线粒体复合物I、II或III的活性和ATP水平,在很大程度上保护线粒体功能免受hIAPP聚集诱导的损伤。数据表明,CHS2有望成为用于治疗2型糖尿病的抗糖尿病药物。

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