Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with persistent colonic inflammation and inadequate therapeutic options. The medicinal and edible plant Polygonatum cyrtonema Hua from Jiuhua Mountain contains polysaccharides with potent anti-inflammatory activities. In this study, a low-molecular-weight fructan (Mw = 2087 Da), designated PCP2, was isolated and purified from its rhizome. Biologically, PCP2 administration markedly alleviated disease severity in dextran sulfate sodium (DSS)-induced colitis mice, as shown by the improvement in multiple indicators of colon injury and inflammation. Fecal microbiota transplantation and antibiotic depletion experiments revealed that the protective effects of PCP2 are mediated through both modulation of the gut microbiota and additional microbiota-independent pathways. Importantly, through molecular dynamics simulations, microscale thermophoresis, and surface plasmon resonance assays, follistatin (Fst) is identified as a direct binding target of PCP2. Functional validation using siRNA-mediated Fst knockdown in Caco-2 cells, combined with adenovirus-mediated knockdown in the murine colon, confirmed that PCP2 exerts its therapeutic effect by directly interacting with Fst and suppressing the BMP4/Smad1/ID1 signaling axis. In summary, PCP2 ameliorates ulcerative colitis via dual mechanisms involving restoration of gut microbiota homeostasis and direct targeting of Fst. These findings establish a novel therapeutic strategy and support the clinical development of P. cyrtonema Hua from Jiuhua Mountain as a functional food for intestinal health.
Data availability
The relevant data can be obtained by the corresponding authors upon reasonable request. The raw 16S rRNA sequencing data and Olink proteomics data are available in the NCBI Sequence Read Archive (SRA) under accession number SUB15811941.
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Acknowledgements
This study was financially supported by the National Natural Science Foundation of China (82270879), the Natural Science Foundation of Anhui Province (2508085QH341), the Natural Science Research Initiative of the Anhui Provincial Department of Education (2024AH040169, 2024AH051934, 2024AH051923), the Research Funding for the Center of Xin’an Medicine and Modernization of Traditional Chinese Medicine at IHM (2023CXMMTCM011), the TCM Innovation and Inheritance Project of Anhui Province (2024CCCX260, 2024CCCX016), the Open Fund of the High-level Key Discipline of Chemistry of Chinese Medicine of the State Administration of Traditional Chinese Medicine, Anhui University of Chinese Medicine (HKDCCM2024008), the Anhui Provincial Postgraduate Education Quality Project (Han Jun Distinguished Mentor Studio) (2023yjsmsgzs037), the Anhui Provincial Pharmacy Graduate Supervisor Team (2023yjsdstd053) and the Chi Zhu Zhi Guang Major Scientific and Technological Achievements Engineering Project of Wuhu City (2023zc06).
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Qiangbao Xu: writing—original draft, validation, formal analysis, data curation, conceptualization. Qiuyue Lv: investigation, formal analysis, data curation, writing—original draft. Zhu Yang: investigation, data curation. Yiping Yang: investigation, data curation. Zihan Li, Yingying Zhang, Sumiao Zhan, Lingzhi Chen, Guodong Wang: investigation. Hui Che: writing—review & editing. Jiangping Wu: writing—review & editing, validation, funding acquisition. Jun Han: visualization, funding acquisition, conceptualization, and writing—review & editing.
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Xu, Q., Lv, Q., Yang, Z. et al. Polygonatum cyrtonema Hua fructan ameliorates ulcerative colitis via gut microbiota modulation and follistatin targeting. npj Sci Food (2026). https://doi.org/10.1038/s41538-026-00729-3
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DOI: https://doi.org/10.1038/s41538-026-00729-3
