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Background <p>Radiotherapy frequently causes intestinal and skeletal damage, so multi-organ protective natural products are needed. Multi-herb formulas are effective due to their bioactive phytochemicals, yet which specific phytochemicals matter and how they work remain unclear.</p> Results <p>In this study, we performed phytochemical profiling of a multi-herb botanical formulation (Beihua decoction, BH) and identified quercetin as a major bioactive flavonoid responsible for protection against radiation-induced gut-bone injury. Phytochemical analysis using ultra-high-performance liquid chromatography coupled with Q-Exactive mass spectrometry (UHPLC-QE-MS) enabled the characterization of multiple constituents and the identification of quercetin as a predominant active component. In a X-ray-irradiated mouse model, quercetin significantly alleviated intestinal injury, restored gut microbiota homeostasis, and improved mucosal barrier integrity. Notably, quercetin promoted the enrichment of short-chain fatty acid-producing bacteria, particularly Butyricimonas, indicating its role in microbiota-mediated intestinal protection. These findings were further supported in lipopolysaccharide (LPS)-stimulated mouse intestinal organoids, where quercetin exhibited anti-inflammatory and epithelial protective effects. In addition, quercetin attenuated radiation-induced trabecular bone damage and suppressed osteoclastogenesis, indicating a dual protective role along the gut–bone axis. Mechanistically, RNA sequencing, confocal microscopy, and molecular dynamics simulations demonstrated that quercetin targets the efferocytosis-associated ligand Growth Arrest-Specific 6 (GAS6) in macrophages, thereby activating the TAM/ELMO1/RAC1 signaling pathway and enhancing macrophage efferocytosis. Enhanced efferocytosis further inhibited macrophage-to-osteoclast differentiation.</p> Conclusion <p>Collectively, this study identifies quercetin as a key bioactive flavonoid mediating gut–bone protection under radiation-induced injury and provides a phytochemical and mechanistic basis for developing plant-derived therapeutics for radiotherapy-associated multi-organ damage.</p> Graphical abstract <p></p>

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Structural characterization and gut-bone protective effects of quercetin from Chinese herbal formula in radiation-induced injury

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月3日

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  • Tongtong Wang,
  • Boyan Xu,
  • Linhui Li,
  • Guoshui Tao,
  • Shu Lu,
  • Junjie Wu,
  • Zhenyu Zhang,
  • Fenglai Yuan,
  • Yahong Zhou,
  • Tianhao Liu,
  • Chenyang Zhang

摘要

Background

Radiotherapy frequently causes intestinal and skeletal damage, so multi-organ protective natural products are needed. Multi-herb formulas are effective due to their bioactive phytochemicals, yet which specific phytochemicals matter and how they work remain unclear.

Results

In this study, we performed phytochemical profiling of a multi-herb botanical formulation (Beihua decoction, BH) and identified quercetin as a major bioactive flavonoid responsible for protection against radiation-induced gut-bone injury. Phytochemical analysis using ultra-high-performance liquid chromatography coupled with Q-Exactive mass spectrometry (UHPLC-QE-MS) enabled the characterization of multiple constituents and the identification of quercetin as a predominant active component. In a X-ray-irradiated mouse model, quercetin significantly alleviated intestinal injury, restored gut microbiota homeostasis, and improved mucosal barrier integrity. Notably, quercetin promoted the enrichment of short-chain fatty acid-producing bacteria, particularly Butyricimonas, indicating its role in microbiota-mediated intestinal protection. These findings were further supported in lipopolysaccharide (LPS)-stimulated mouse intestinal organoids, where quercetin exhibited anti-inflammatory and epithelial protective effects. In addition, quercetin attenuated radiation-induced trabecular bone damage and suppressed osteoclastogenesis, indicating a dual protective role along the gut–bone axis. Mechanistically, RNA sequencing, confocal microscopy, and molecular dynamics simulations demonstrated that quercetin targets the efferocytosis-associated ligand Growth Arrest-Specific 6 (GAS6) in macrophages, thereby activating the TAM/ELMO1/RAC1 signaling pathway and enhancing macrophage efferocytosis. Enhanced efferocytosis further inhibited macrophage-to-osteoclast differentiation.

Conclusion

Collectively, this study identifies quercetin as a key bioactive flavonoid mediating gut–bone protection under radiation-induced injury and provides a phytochemical and mechanistic basis for developing plant-derived therapeutics for radiotherapy-associated multi-organ damage.

Graphical abstract