β-glucosidase-mediated hydrolysis of Ophiocordyceps polysaccharides enhances antioxidant and immunomodulatory activities and ameliorates intestinal barrier function to maintain gut homeostasis
Abstract
Polysaccharides derived from Ophiocordyceps (Chinese Cordyceps) exhibit notable bioactivities, yet their high molecular weight may limit their fermentability by the gut microbiota, thereby modulating the production of bioactive metabolites. This study aimed to prepare low-molecular-weight Ophiocordyceps polysaccharides (OPs) through enzymatic modification and to elucidate the associated structural alterations and mechanisms underlying intestinal barrier regulation. Hydrolysis with β-glucosidase yielded the enzymatically modified product OPs-80E. Structural characterization demonstrated that hydrolysis significantly reduced the average molecular weight from 8.64 × 105 Da to 2.99 × 104 Da and altered the monosaccharide composition profile. In vitro assays showed that OPs-80E exhibited greater antioxidant capacity and immunomodulatory activity than native OPs-80, as evidenced by enhanced RAW264.7 cell proliferation, phagocytosis, and cytokine secretion. In a cyclophosphamide-induced immunosuppressed mouse model, OPs-80E was more effective than OPs-80 in reversing intestinal histopathological damage, significantly upregulating the expression of tight junction proteins (ZO-1 and Claudin-1), and remodeling the gut microbiota architecture. 16S rRNA gene sequencing analysis indicated that OPs-80E significantly enriched butyrate-producing taxa, such as Lachnospiraceae, while suppressing potential pathogens. Correlation network analysis further revealed that OPs-80E established a symbiotic network centered on the Prevotellaceae Ga6A1 group and Clade Ia, facilitating synergistic “polysaccharide degradation and butyrate production” metabolic cross-feeding to maintain intestinal barrier integrity. Collectively, enzymatic hydrolysis represents an effective strategy for enhancing the bioactivity of Chinese Cordyceps polysaccharides. OPs-80E exerts intestinal protective effects by modulating the “microbiota and barrier” axis, highlighting its broad application prospects in functional foods and pharmaceutical development.
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BibTeX
@article{bian2026βglucosidasemediated,
title = {{β-glucosidase-mediated hydrolysis of Ophiocordyceps polysaccharides enhances antioxidant and immunomodulatory activities and ameliorates intestinal barrier function to maintain gut homeostasis}},
author = {Zhiying Bian and Anhui Zhao and Liyuan Jiang and Yi Ruan and Xiaochun Yue and Jiawei Fang and Jing Bai and Shuqi Niu and Sijing Liu and Jinlin Guo},
journal = {Frontiers in Pharmacology},
year = {2026},
month = nov,
doi = {10.3389/fphar.2026.1957172},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1957172},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - β-glucosidase-mediated hydrolysis of Ophiocordyceps polysaccharides enhances antioxidant and immunomodulatory activities and ameliorates intestinal barrier function to maintain gut homeostasis
AU - Zhiying Bian
AU - Anhui Zhao
AU - Liyuan Jiang
AU - Yi Ruan
AU - Xiaochun Yue
AU - Jiawei Fang
AU - Jing Bai
AU - Shuqi Niu
AU - Sijing Liu
AU - Jinlin Guo
PY - 2026
DA - 2026/11/05
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1957172
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1957172
AB - Polysaccharides derived from Ophiocordyceps (Chinese Cordyceps) exhibit notable bioactivities, yet their high molecular weight may limit their fermentability by the gut microbiota, thereby modulating the production of bioactive metabolites. This study aimed to prepare low-molecular-weight Ophiocordyceps polysaccharides (OPs) through enzymatic modification and to elucidate the associated structural alterations and mechanisms underlying intestinal barrier regulation. Hydrolysis with β-glucosidase yielded the enzymatically modified product OPs-80E. Structural characterization demonstrated that hydrolysis significantly reduced the average molecular weight from 8.64 × 105 Da to 2.99 × 104 Da and altered the monosaccharide composition profile. In vitro assays showed that OPs-80E exhibited greater antioxidant capacity and immunomodulatory activity than native OPs-80, as evidenced by enhanced RAW264.7 cell proliferation, phagocytosis, and cytokine secretion. In a cyclophosphamide-induced immunosuppressed mouse model, OPs-80E was more effective than OPs-80 in reversing intestinal histopathological damage, significantly upregulating the expression of tight junction proteins (ZO-1 and Claudin-1), and remodeling the gut microbiota architecture. 16S rRNA gene sequencing analysis indicated that OPs-80E significantly enriched butyrate-producing taxa, such as Lachnospiraceae, while suppressing potential pathogens. Correlation network analysis further revealed that OPs-80E established a symbiotic network centered on the Prevotellaceae Ga6A1 group and Clade Ia, facilitating synergistic “polysaccharide degradation and butyrate production” metabolic cross-feeding to maintain intestinal barrier integrity. Collectively, enzymatic hydrolysis represents an effective strategy for enhancing the bioactivity of Chinese Cordyceps polysaccharides. OPs-80E exerts intestinal protective effects by modulating the “microbiota and barrier” axis, highlighting its broad application prospects in functional foods and pharmaceutical development.
SN - 1663-9812
ER -