Journal Article

Structural Characterization and Anti-Colitis Mechanisms of Polygonatum sibiricum Polysaccharides via Modulation of Neutrophil Extracellular Traps (NETs)—Macrophage Crosstalk

Xia, Daozong, Li, Fenfen, Zhang, Lu, Wu, Chenxi, Xu, Jiaman, Zhang, Xiaoxi, Qiu, Yu, Zheng, Junna, Ke, Wukang

2026

Overview

Background: Polygonatum sibiricum (PS), a perennial herbaceous plant belonging to the Liliaceae family, is widely distributed in China and other East Asian countries. PS has been used as food and medicine for thousands of years, and its rhizomes are rich in Polygonatum sibiricum polysaccharides (PSP), which exhibit various bioactivities, yet their structural features and therapeutic mechanisms against ulcerative colitis (UC) remain unclear. Methods: A homogeneous polysaccharide, PSP-1b (57.45 kDa), was isolated from the rhizomes of PS via ion-exchange and gel filtration chromatography and structurally characterized using chromatographic and spectroscopic methods. In vivo, its effects were evaluated in a dextran sulfate sodium (DSS)-induced mouse model of UC, while in vitro mechanisms were explored using macrophages stimulated with lipopolysaccharide (LPS) and neutrophil extracellular traps (NETs). Results: PSP-1b was identified as a neutral polysaccharide with minimal branching. Its primary structural backbone was largely composed of →4)-β-D-Galp-(1→ residues. A portion of these backbone residues was substituted at the O-6 position by side chains primarily composed of β-D-Galp-(1→ units. In vivo, PSP-1b significantly alleviated DSS-induced colitis by reducing inflammatory cytokine secretion, suppressing colonic macrophage infiltration, and reversing neutrophil extracellular traps (NETs) deposition. In vitro, PSP-1b directly interacted with TLR4, inhibited the MAPK/NF-κB signaling pathway, and attenuated LPS- and NET-induced macrophage polarization and inflammation. Conclusions: PSP-1b as a promising candidate for functional foods or therapeutic agents targeting inflammatory bowel disease.

• Publisher: MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
• Subject: Animals / Anti-Inflammatory Agents - chemistry / Anti-Inflammatory Agents - pharmacology / Antibodies / Chinese history / Chromatography / Colitis, Ulcerative - chemically induced / Colitis, Ulcerative - drug therapy / Cytokines / Dextran / Dextran Sulfate / Diarrhea / Disease Models, Animal / Extracellular Traps - drug effects / Extracellular Traps - metabolism / Functional foods / Health aspects / Inflammation / Inflammatory bowel disease / Liu, Timothy / Macrophages / Macrophages - drug effects / Macrophages - metabolism / Male / Mice / Mice, Inbred C57BL / Molecular weight / Neutrophils / Neutrophils - drug effects / Polygonatum - chemistry / Polysaccharides - chemistry / Polysaccharides - isolation & purification / Polysaccharides - pharmacology / Proteins / RAW 264.7 Cells / Rhizome - chemistry / Signal Transduction - drug effects / Sulfates / Traditional Chinese medicine / Ulcerative colitis