积雪草中含 RG-I 的糖域与 galectin-3 紧密结合,抑制细胞与细胞之间的相互作用

IF 5.2 2区 农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY Chemical and Biological Technologies in Agriculture Pub Date : 2024-07-27 DOI:10.1186/s40538-024-00615-8
Xuejiao Xu, Zhen He, Xinlin Luo, Jiaqi Peng, Xin Ning, Kevin H. Mayo, Guihua Tai, Mengshan Zhang, Yifa Zhou
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引用次数: 0

摘要

积雪草已被证明对治疗肿瘤有益。然而,其活性成分和分子作用机制尚未完全阐明。果胶多糖是药用植物的主要活性成分。此外,这些多糖还被认为是一般会促进肿瘤生长的半凝集素(如半凝集素-1、-3、-7)的潜在抑制剂。然而,目前还缺乏对积雪草果胶多糖的详细结构分析,以及它们与半凝集素相互作用的知识。通过阴离子交换色谱和凝胶渗透色谱相结合的方法,从积雪草中分离出的水溶性果胶多糖(WCAP)被纯化成两个均一的馏分(WCAP-A2b 和 WCAP-A5b)。研究人员利用单糖组成、傅立叶变换红外光谱、核磁共振和酶学分析来确定它们的结构特征。此外,还利用血凝法和生物层干涉测量法评估了半凝集素-1、-3、-7 与一系列这些多糖(包括两种果胶组分及其经酶水解产生的结构域)之间的相互作用。WCAP-A2b 和 WCAP-A5b 的重量平均分子量分别为 30.0 kDa 和 34.0 kDa,这两种多糖都由鼠李糖半乳糖醛酸 I(RG-I)、鼠李糖半乳糖醛酸 II(RG-II)和均半乳糖醛酸(HG)结构域组成,质量比分别为 1.3:1.0:1.4 和 1.1:1.0:2.4。它们的 RG-I 结构域含有阿拉伯聚糖、半乳糖和/或阿拉伯半乳糖,以及中性糖侧链,这些糖侧链在 WCAP-A2b 中比在 WCAP-A5b 中更为普遍。血凝和生物层干涉测量结合试验表明,相对于galectin-1和-7,galectin-3能与WCAP-A5b中的RG-I结构域紧密结合(可能是通过其中性侧链),从而抑制galectin-3介导的细胞-细胞相互作用。我们的研究提供了积雪草果胶多糖的结构信息。研究结果表明,WCAP-A5b 和 WCAP-A2b 中的 RG-I 结构域可被开发为抑制 galectin-3 介导的细胞-细胞粘附和肿瘤生长的潜在抑制剂。
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RG-I-containing sugar domains from Centella Asiatica bind strongly to galectin-3 to inhibit cell–cell interactions

Background

Centella Asiatica has been shown to have beneficial value for the treatment of tumors. However, its active ingredients and molecular mechanisms of action have not been fully elucidated. Pectic polysaccharides are the primary active components from medicinal plants. Moreover, these polysaccharides are regarded as potential inhibitors of galectins, such as galectin-1, -3, -7, that generally promote tumor growth. Nevertheless, detailed structural analysis of pectic polysaccharides from Centella Asiatica is sorely lacking, as is knowledge of their interactions with galectins.

Methods

Water-soluble pectic polysaccharides (WCAP) isolated from Centella Asiatica were purified into two homogeneous fractions (WCAP-A2b and WCAP-A5b) by a combination of anion-exchange and gel-permeation chromatography. Monosaccharide composition, FT-IR, NMR and enzymatic analyses were used to characterize their structural features. Furthermore, the interactions between galectin-1, -3, -7 and a series of these polysaccharides, including two pectin fractions and their structural domains produced by enzymatic hydrolysis, were evaluated by using hemagglutination and biolayer interferometry.

Results

WCAP-A2b and WCAP-A5b have weight averaged molecular weights of 30.0 kDa and 34.0 kDa, respectively, and both polysaccharides consist of rhamnogalacturonan I (RG-I), rhamnogalacturonan II (RG-II) and homogalacturonan (HG) domains, with mass ratios of 1.3: 1.0: 1.4 and 1.1: 1.0: 2.4, respectively. Their RG-I domains contain arabinan, galactan, and/or arabinogalactan, along with neutral sugar side chains that are more prevalent in WCAP-A2b than in WCAP-A5b. Hemagglutination and biolayer interferometry binding assays indicate that galectin-3 vis-à-vis galectin-1 and -7, binds strongly to the RG-I domain (likely via its neutral side chains) in WCAP-A5b, thereby inhibiting galectin-3-mediated cell–cell interactions.

Conclusions

Our study provides structural information on pectin polysaccharides from Centella Asiatica. Results suggest that RG-I domains from WCAP-A5b and WCAP-A2b may be developed as potential inhibitors of galectin-3-mediated cell–cell adhesion and tumor growth.

Graphical Abstract

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来源期刊
Chemical and Biological Technologies in Agriculture
Chemical and Biological Technologies in Agriculture Biochemistry, Genetics and Molecular Biology-Biotechnology
CiteScore
6.80
自引率
3.00%
发文量
83
审稿时长
15 weeks
期刊介绍: Chemical and Biological Technologies in Agriculture is an international, interdisciplinary, peer-reviewed forum for the advancement and application to all fields of agriculture of modern chemical, biochemical and molecular technologies. The scope of this journal includes chemical and biochemical processes aimed to increase sustainable agricultural and food production, the evaluation of quality and origin of raw primary products and their transformation into foods and chemicals, as well as environmental monitoring and remediation. Of special interest are the effects of chemical and biochemical technologies, also at the nano and supramolecular scale, on the relationships between soil, plants, microorganisms and their environment, with the help of modern bioinformatics. Another special focus is the use of modern bioorganic and biological chemistry to develop new technologies for plant nutrition and bio-stimulation, advancement of biorefineries from biomasses, safe and traceable food products, carbon storage in soil and plants and restoration of contaminated soils to agriculture. This journal presents the first opportunity to bring together researchers from a wide number of disciplines within the agricultural chemical and biological sciences, from both industry and academia. The principle aim of Chemical and Biological Technologies in Agriculture is to allow the exchange of the most advanced chemical and biochemical knowledge to develop technologies which address one of the most pressing challenges of our times - sustaining a growing world population. Chemical and Biological Technologies in Agriculture publishes original research articles, short letters and invited reviews. Articles from scientists in industry, academia as well as private research institutes, non-governmental and environmental organizations are encouraged.
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