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A β-glucan from Grifola frondosa effectively delivers therapeutic oligonucleotide into cells via dectin-1 receptor and attenuates TNFα gene expression

Cui, Hao, Zhu, Xinying, Huo, Zhengyi, Liao, Bingbing, Huang, Jingping, Wang, Zhenxing, Song, Chunhui, Hu, Xiangguo, Fang, Jianping
International journal of biological macromolecules 2020 v.149 pp. 801-808
Fourier transform infrared spectroscopy, Grifola frondosa, beta-glucans, bioactive properties, fruiting bodies, gene expression, inflammation, macrophages, medicinal fungi, moieties, molecular weight, neoplasms, nuclear magnetic resonance spectroscopy, nutritive value, oligonucleotides, secretion, sodium hydroxide, therapeutics, tumor necrosis factor-alpha
Grifola frondosa is an edible and medicinal mushroom with great nutritional values and bioactivities. In the present study, a soluble homogeneous β-glucan, GFPS, with high molecular mass of 5.42 × 10⁶ Da was purified from the fruit bodies of Grifola frondosa using 5% cold NaOH. The structure of GFPS was determined with FT-IR, NMR, and monosaccharide composition analysis, and was identified to be a β-D-(1-3)-linked glucan backbone with a single β-D-(1-6)-linked glucopyranosyl residue branched at C-6 on every third residue. Our results indicated that GFPS had a triple helical structure and could form complex with polydeoxyadenylic acid (poly[A]). Further studies demonstrated that GFPS could interact with poly[A] moiety of a designed antisense oligonucleotide (ASO) targeting the primary transcript of proinflammatory cytokine TNFα (TNFα-A60). This GFPS-based complex could incorporate TNFα-A60 into the macrophage cells via dectin-1 receptor and attenuate lipopolysaccharide-induced secretion of TNFα. Our results suggested that GFPS could be applied to deliver therapeutic oligonucleotides for the treatment of diseases such as inflammation and cancers.