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羊肚菌子实体中一种新的含 GlcNAc 的多糖:结构特征及体内外免疫调节活性。

A new GlcNAc-containing polysaccharide from Morchella importuna fruiting bodies: Structural characterization and immunomodulatory activities in vitro and in vivo.

机构信息

Department of Pharmacology, Jinan University 601 Huangpu Avenue West, Guangzhou 510632, China.

Biotechnological Institute of Chinese Materia Medica, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China.

出版信息

Int J Biol Macromol. 2021 Dec 1;192:1134-1149. doi: 10.1016/j.ijbiomac.2021.10.051. Epub 2021 Oct 15.

Abstract

This study investigated the purification and characterization of a new immunomodulatory GlcNAc-containing polysaccharide (MIPB70-1) from Morchella importuna with molecular weights of 20.6 kDa. Structural analysis indicated that MIPB70-1 was composed of GlcNAc:Gal:Glc:Man with molar ratios of 1.00:7.16:5.54:5.61, and its primary structure was characterized as a repeating unit consisting of →6)-α-D-Glcp-(1→, α-D-GlcpNAc-(1→, α-D-Galp-(1→, β-D-Glcp-(1→, →6)-α-D-Manp-(1→, →4)-α-D-GlcpNAc-(1→, →4)-β-D-Glcp-(1→, →3,6)-α-D-Manp-(1→, →2)-α-D-Galp-(1→, →2,3,6)-α-D-Manp-(1→. Immunological assays indicated that MIPB70-1 enhanced the phagocytic function and promoted the secretion of nitric oxide (NO) as well as cytokines through targeting Toll-like receptor 4 (TLR4) on macrophage membrane and activating the downstream signaling pathways in RAW 264.7 cells. MIPB70-1 regulated mouse immunity to counteract the immune damage caused by the chemotherapy drug cyclophosphamide (CTX) in vivo. Furthermore, MIPB70-1 enhanced the anti-tumor activity of doxorubicin (DOX) and inhibited the growth of tumors, by immunomodulation in the orthotopic murine model of 4T1 breast cancer. These results demonstrate the potential of this GlcNAc-containing polysaccharide as an immune enhancer.

摘要

本研究从羊肚菌中提取了一种新型免疫调节 GlcNAc 多糖(MIPB70-1),其分子量为 20.6 kDa。结构分析表明,MIPB70-1 由 GlcNAc:Gal:Glc:Man 组成,摩尔比为 1.00:7.16:5.54:5.61,其一级结构特征为重复单元,由 →6)-α-D-Glcp-(1→、α-D-GlcpNAc-(1→、α-D-Galp-(1→、β-D-Glcp-(1→、→6)-α-D-Manp-(1→、→4)-α-D-GlcpNAc-(1→、→4)-β-D-Glcp-(1→、→3,6)-α-D-Manp-(1→、→2)-α-D-Galp-(1→、→2,3,6)-α-D-Manp-(1→组成。免疫测定表明,MIPB70-1 通过靶向巨噬细胞膜上的 Toll 样受体 4(TLR4)并激活 RAW 264.7 细胞中的下游信号通路,增强吞噬功能,促进一氧化氮(NO)和细胞因子的分泌。MIPB70-1 调节小鼠免疫,以抵消体内化疗药物环磷酰胺(CTX)引起的免疫损伤。此外,MIPB70-1 通过在 4T1 乳腺癌的原位小鼠模型中进行免疫调节,增强阿霉素(DOX)的抗肿瘤活性并抑制肿瘤生长。这些结果表明,这种含 GlcNAc 的多糖具有作为免疫增强剂的潜力。

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