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<p><i>Lentinula edodes</i> (<i>L. edodes</i>) polysaccharides hold therapeutic potential for hyperuricemia (HUA), but their mechanisms remain unclear. This study investigated the anti-HUA effects and associated regulatory pathways of two structurally distinct polysaccharides (LEP20 and LEP50) from <i>L. edodes</i>. Structural analysis identified LEP20 as a (1 → 3)-<i>β</i>-D-glucan (<i>M</i><sub><i>w</i></sub>, 1.96×10<sup>6 </sup>g/mol) and LEP50 as a (1 → 4)-<i>α</i>-D-glucan (<i>M</i><sub><i>w</i></sub>, 1.46×10<sup>7 </sup>g/mol). In a HUA rat model, both LEP20 and LEP50 significantly reduced serum UA level, inhibited xanthine oxidase, and alleviated renal injury and inflammation. Mechanistically, LEP20 was linked to modulate the gut-kidney axis by regulating UA transporters, enriching beneficial gut microbiota (e.g., <i>Blautia_luti</i>), and promoting short-chain fatty acid production to restore intestinal barrier integrity. In contrast, LEP50 primarily regulated systemic purine metabolism, directly reducing hypoxanthine levels and modulating specific gut microbes (e.g., <i>Romboutsia_ilealis</i>). The distinct structural features of these polysaccharides are associated with different regulatory pathways, supporting their potential application in HUA management.</p>

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Structural divergence of lentinula edodes polysaccharides is associated with distinct anti-hyperuricemia pathways

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月16日

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  • Xinyi Xiong,
  • Peng Liu,
  • Liping Liu,
  • Jie Feng,
  • Jingsong Zhang,
  • Jinyan Wang,
  • Jie Geng,
  • Yanfang Liu

摘要

Lentinula edodes (L. edodes) polysaccharides hold therapeutic potential for hyperuricemia (HUA), but their mechanisms remain unclear. This study investigated the anti-HUA effects and associated regulatory pathways of two structurally distinct polysaccharides (LEP20 and LEP50) from L. edodes. Structural analysis identified LEP20 as a (1 → 3)-β-D-glucan (Mw, 1.96×106 g/mol) and LEP50 as a (1 → 4)-α-D-glucan (Mw, 1.46×107 g/mol). In a HUA rat model, both LEP20 and LEP50 significantly reduced serum UA level, inhibited xanthine oxidase, and alleviated renal injury and inflammation. Mechanistically, LEP20 was linked to modulate the gut-kidney axis by regulating UA transporters, enriching beneficial gut microbiota (e.g., Blautia_luti), and promoting short-chain fatty acid production to restore intestinal barrier integrity. In contrast, LEP50 primarily regulated systemic purine metabolism, directly reducing hypoxanthine levels and modulating specific gut microbes (e.g., Romboutsia_ilealis). The distinct structural features of these polysaccharides are associated with different regulatory pathways, supporting their potential application in HUA management.