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药用层孔菌抗肿瘤活性多糖通过激活免疫和抑制血管生成。

An antitumor fungal polysaccharide from Fomitopsis officinalis by activating immunity and inhibiting angiogenesis.

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.

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.

出版信息

Int J Biol Macromol. 2024 May;267(Pt 2):131320. doi: 10.1016/j.ijbiomac.2024.131320. Epub 2024 Apr 1.

Abstract

Macrofungi, a class of unique natural resources, are gaining popularity owing to their potential therapeutic benefits and edibility. From Fomitopsis officinalis, a medicinal macrofungus with anticancer activity, a homogeneous heteropolysaccharide (FOBP50-1) with a molecular weight of 2.21 × 10 g/mol has been extracted and purified. FOBP50-1 was found to be composed of 3-O-methylfucose, fucose, mannose, glucose, and galactose with a ratio of 1: 6.5: 4.4: 8.1: 18.2. The sugar fragments and structure of FOBP50-1 were investigated, which included →6)-α-d-Galp-(1→, →2,6)-α-d-Galp-(1→, →3)-α-l-Fucp-(1→, α-d-Glcp-(1→, →3)-β-d-Manp-(1→, →6)-β-d-Manp-(1→, 3-O-Me-α-l-Fucp-(1→, according to the UV, FT-IR, GC-MS, and NMR data. Besides the structure elucidation, FOBP50-1 showed promising antitumor activity in the zebrafish assays. The following mechanism examination discovered that FOBP50-1 interacted with TLR-4, PD-1, and VEGF to activate immunity and inhibit angiogenesis according to a series of cell, transgenic zebrafish, and surface plasmon resonance (SPR) experiments. The K values indicating the association of FOBP50-1 with TLR-4, PD-1, and VEGF, were 4.69 × 10, 7.98 × 10, 3.04 × 10 M, respectively, in the SPR experiments. All investigations have demonstrated that the homogenous fungal polysaccharide FOBP50-1 has the potential to be turned into a tumor immunotherapy agent.

摘要

大型真菌作为一类独特的自然资源,由于其潜在的治疗益处和可食用性而受到关注。从具有抗癌活性的药用大型真菌——灰树花中提取并纯化得到了一种均一的杂多糖(FOBP50-1),其分子量为 2.21×10 g/mol。FOBP50-1 由 3-O-甲基岩藻糖、岩藻糖、甘露糖、葡萄糖和半乳糖组成,摩尔比为 1:6.5:4.4:8.1:18.2。根据 UV、FT-IR、GC-MS 和 NMR 数据,对 FOBP50-1 的糖片段和结构进行了研究,包括→6)-α-d-Galp-(1→、→2,6)-α-d-Galp-(1→、→3)-α-l-Fucp-(1→、α-d-Glcp-(1→、→3)-β-d-Manp-(1→、→6)-β-d-Manp-(1→、3-O-Me-α-l-Fucp-(1→。除了结构阐明外,FOBP50-1 在斑马鱼试验中显示出有希望的抗肿瘤活性。随后的机制研究发现,根据一系列细胞、转基因斑马鱼和表面等离子体共振(SPR)实验,FOBP50-1 通过与 TLR-4、PD-1 和 VEGF 相互作用来激活免疫并抑制血管生成。SPR 实验中,FOBP50-1 与 TLR-4、PD-1 和 VEGF 的结合 K 值分别为 4.69×10、7.98×10、3.04×10 M。所有的研究都表明,均一的真菌多糖 FOBP50-1 有可能成为一种肿瘤免疫治疗药物。

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