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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

Author:
Cui, Hao, Zhu, Xinying, Huo, Zhengyi, Liao, Bingbing, Huang, Jingping, Wang, Zhenxing, Song, Chunhui, Hu, Xiangguo, Fang, Jianping
Source:
International journal of biological macromolecules 2020 v.149 pp. 801-808
ISSN:
0141-8130
Subject:
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
Abstract:
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.
Agid:
6835155