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药用层孔菌真菌多糖作为一种多靶点分子来对抗癌症。

A fungal polysaccharide from Fomitopsis officinalis as a multi-target molecule to combat cancer.

机构信息

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China.

Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Tianjin 301617, People's Republic of China.

出版信息

Int J Biol Macromol. 2024 Jun;272(Pt 1):132543. doi: 10.1016/j.ijbiomac.2024.132543. Epub 2024 May 23.

DOI:10.1016/j.ijbiomac.2024.132543
PMID:38788870
Abstract

Some macrofungi have a long history of being used as traditional or folk medicines, making significant contributions to human health. To discover bioactive molecules with potential anticancer properties, a homogeneous heteropolysaccharide (FOBP90-1) was purified from the medicinal macrofungus Fomitopsis officinalis. FOBP90-1 was found to have a molecular weight of 2.87 × 10 g/mol and mainly consist of →6)-α-d-Galp-(1→, →2,6)-α-d-Galp-(1→, →3)-α-l-Fucp-(1→, →6)-β-d-Glcp-(1→, α-d-Manp-(1→, and 3-O-Me-α-l-Fucp-(1→ according to UV, FT-IR, methylation analysis, and NMR data. In addition to its structural properties, FOBP90-1 displayed anticancer activity in zebrafish models. The following mechanistic analysis discovered that the in vivo antitumor effect was linked to immune activation and angiogenesis inhibition. These effects were mediated by the interactions of FOBP90-1 with TLR-2, TLR-4, PD-L1, and VEGFR-2, as determined through a series of experiments involving cells, transgenic zebrafish, molecular docking simulations, and surface plasmon resonance (SPR). All the experimental findings have demonstrated that FOBP90-1, a purified fungal polysaccharide, is expected to be utilized as a cancer treatment agent.

摘要

一些大型真菌具有作为传统或民间药物使用的悠久历史,为人类健康做出了重大贡献。为了发现具有潜在抗癌特性的生物活性分子,从药用大型真菌红栓菌中纯化出一种均一的杂多糖(FOBP90-1)。FOBP90-1 的分子量为 2.87×10 g/mol,主要由 →6)-α-d-Galp-(1→、→2,6)-α-d-Galp-(1→、→3)-α-l-Fucp-(1→、→6)-β-d-Glcp-(1→、α-d-Manp-(1→和 3-O-Me-α-l-Fucp-(1→组成,根据 UV、FT-IR、甲基化分析和 NMR 数据得出。除了其结构特性外,FOBP90-1 在斑马鱼模型中表现出抗癌活性。以下机制分析发现,体内抗肿瘤作用与免疫激活和血管生成抑制有关。这些作用是通过 FOBP90-1 与 TLR-2、TLR-4、PD-L1 和 VEGFR-2 的相互作用介导的,这是通过一系列涉及细胞、转基因斑马鱼、分子对接模拟和表面等离子体共振(SPR)的实验确定的。所有的实验结果都表明,FOBP90-1 作为一种纯化的真菌多糖,有望被用作癌症治疗剂。

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