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