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<p>A novel pectic polysaccharide with dual backbones (SHP-A, 15,866 Da) was isolated from Sinopodophyllum hexandrum fruits. This polysaccharide is a heteropolymer composed of six monosaccharides. Structural characterization based on nuclear magnetic resonance spectroscopy, methylation analysis, and other methods demonstrated that SHP-A features a unique architecture consisting of a rhamnogalacturonan-I backbone (alternating α-GalpA and α-Rha molecules with β-Galp/α-Araf side chains) and a β-glucomannan backbone (alternating β-Manp and β-Glcp molecules), interconnected via β-Galp bridges. Bioactivity assays showed that SHP-A exerts potent immunomodulatory effects by enhancing macrophage phagocytosis and nitric oxide release. Transcriptomics analyses and NOD1 inhibitor interventions confirmed that SHP-A can activate the NOD1/RIPK2/NF-κB axis and induce M1 polarization in RAW264.7 macrophages, thereby upregulating various cytokines and chemokines. Furthermore, SHP-A also appeared to enhance immune function through mitochondrial metabolism, which indicated its potential as an immunomodulatory agent that can be used in the development of immune-enhancing health foods in the future.</p><p></p>

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Dual-backbone pectic polysaccharide activates NOD1/RIPK2/NF-κB and mitochondrial metabolism to enhance the immune activity of macrophages

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月8日

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  • Ziwei Liu,
  • Hangyu Li,
  • Shuyao Yang,
  • Xinnan Zhang,
  • Qianqian Liu,
  • Yuan Xu,
  • Yanwen Yang,
  • Yi Liao,
  • Yao Wang,
  • Haibo Feng

摘要

A novel pectic polysaccharide with dual backbones (SHP-A, 15,866 Da) was isolated from Sinopodophyllum hexandrum fruits. This polysaccharide is a heteropolymer composed of six monosaccharides. Structural characterization based on nuclear magnetic resonance spectroscopy, methylation analysis, and other methods demonstrated that SHP-A features a unique architecture consisting of a rhamnogalacturonan-I backbone (alternating α-GalpA and α-Rha molecules with β-Galp/α-Araf side chains) and a β-glucomannan backbone (alternating β-Manp and β-Glcp molecules), interconnected via β-Galp bridges. Bioactivity assays showed that SHP-A exerts potent immunomodulatory effects by enhancing macrophage phagocytosis and nitric oxide release. Transcriptomics analyses and NOD1 inhibitor interventions confirmed that SHP-A can activate the NOD1/RIPK2/NF-κB axis and induce M1 polarization in RAW264.7 macrophages, thereby upregulating various cytokines and chemokines. Furthermore, SHP-A also appeared to enhance immune function through mitochondrial metabolism, which indicated its potential as an immunomodulatory agent that can be used in the development of immune-enhancing health foods in the future.