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普通念珠藻免疫调节多糖的结构解析及分子机制

Structure elucidation and molecular mechanism of an immunomodulatory polysaccharide from Nostoc commune.

作者信息

Yang Yiting, Ren Ping, Sun Ying, Li Junyi, Zhou Xinjun, Zhang Haipeng, He Chengguang, Dai Huining, Guan Lili

机构信息

College of Life Sciences, Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, Jilin Agricultural University, Changchun 130118, Jilin, China.

College of Life Sciences, Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, Jilin Agricultural University, Changchun 130118, Jilin, China.

出版信息

Int J Biol Macromol. 2024 Dec;283(Pt 1):137435. doi: 10.1016/j.ijbiomac.2024.137435. Epub 2024 Nov 12.

DOI:10.1016/j.ijbiomac.2024.137435
PMID:39537070
Abstract

Nostoc commune Vaucher, a terrestrial and benthic blue-green alga, widely used in food and medicine worldwide. N. commune Polysaccharides (NCVP) have excellent biological activities, especially immunomodulatory, hypoglycemic and anti-tumor activities. However, the mechanism and structure-activity relationship of NCVP has been less studied. In this study, based on methylation and NMR results, a novel polysaccharide NCVP2 with 135 kDa, containing→4)-α-D-Galp-(1→, → 4)-β-D-Glcp-(1→, and →4)-α-D-Xylp-(1→ residues as the backbon, was sequentially purified from N.commune by DEAE-52 and Sephadex G-100 column. NCVP2 (50 μg/mL) exhibited the strong in vitro immunomodulatory activity by promoting the generation of nitric oxide (NO) and reactive oxygen species (ROS). A total of 2048 differentially expressed genes (DEGs) were identified by RNA-seq, including 1019 down-regulated genes and 1065 up-regulated genes. These DEGs were mainly enriched in the immune-related biological processes, involving in Mitogen-activated protein kinase (MAPK) and Toll-like receptor (TLR) signaling pathways by GO and KEGG enrichment analysis. Furthermore, Western blot results proved NCVP2 could recognize TLR2 and TLR4/MD2, and regulate TLR7/IRF7, MAPK and PI3K/AKT signaling pathways. In summary, a novel polysaccharide NCVP2 from N.commune was proposed to exhibit significant immunomodulatory effects with multiple-paths and targets, and has great potential in the development of healthy foods such as immunomodulators.

摘要

普通念珠藻,一种陆生和底栖蓝藻,在全球范围内广泛用于食品和医药领域。普通念珠藻多糖(NCVP)具有优异的生物活性,尤其是免疫调节、降血糖和抗肿瘤活性。然而,NCVP的作用机制和构效关系研究较少。本研究基于甲基化和核磁共振结果,通过DEAE-52和Sephadex G-100柱从普通念珠藻中依次纯化出一种新型多糖NCVP2,其分子量为135 kDa,含有→4)-α-D-吡喃半乳糖-(1→、→4)-β-D-吡喃葡萄糖-(1→和→4)-α-D-吡喃木糖-(1→残基作为主链。NCVP2(50μg/mL)通过促进一氧化氮(NO)和活性氧(ROS)的产生表现出强大的体外免疫调节活性。通过RNA测序鉴定出总共2048个差异表达基因(DEG),包括1019个下调基因和1065个上调基因。通过GO和KEGG富集分析,这些DEG主要富集在免疫相关的生物学过程中,涉及丝裂原活化蛋白激酶(MAPK)和Toll样受体(TLR)信号通路。此外,蛋白质印迹结果证明NCVP2可以识别TLR2和TLR4/MD2,并调节TLR7/IRF7、MAPK和PI3K/AKT信号通路。综上所述,提出了一种来自普通念珠藻的新型多糖NCVP2,它具有多途径和多靶点的显著免疫调节作用,在免疫调节剂等健康食品的开发中具有巨大潜力。

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