Qingjie Fuzheng Granule prevents colitis-associated colorectal cancer by inhibiting abnormal activation of NOD2/NF-<i>κ</i>B signaling pathway mediated by gut microbiota disorder.

Bin HUANG; Honglin AN; Mengxuan GUI; Yiman QIU; Wen XU; Liming CHEN; Qiang LI; Shaofeng YAO; Shihan LIN; Tatyana Aleksandrovna KHRUSTALEVA; Ruiguo WANG; Jiumao LIN

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Qingjie Fuzheng Granule prevents colitis-associated colorectal cancer by inhibiting abnormal activation of NOD2/NF-κB signaling pathway mediated by gut microbiota disorder.

Author: Bin HUANG ¹ ; Honglin AN ¹ ; Mengxuan GUI ¹ ; Yiman QIU ¹ ; Wen XU ² ; Liming CHEN ¹ ; Qiang LI ³ ; Shaofeng YAO ¹ ; Shihan LIN ² ; Tatyana Aleksandrovna KHRUSTALEVA ⁴ ; Ruiguo WANG ⁵ ; Jiumao LIN ¹
Author Information

1. Academy of Integrative Medicine of Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
2. College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
3. The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
4. Multidisciplinary Diagnostic Laboratory, Institute of Physiology of National Academy of Sciences of Belarus, Minsk 37517, Belarus.
5. Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
Publication Type:Journal Article
Keywords: NOD2/NF-κB pathway; Qingjie Fuzheng Granule; T cells; colitis-associated colorectal cancer; gut microbiota
From: Chinese Herbal Medicines 2025;17(3):500-512
CountryChina
Language:English
Abstract: OBJECTIVE:This study investigates the efficacy and mechanisms of Qingjie Fuzheng Granules (QFG) in inhibiting colitis-associated colorectal cancer (CAC) development via RNA sequencing (RNA-seq) and 16S ribosomal RNA (rRNA) correlation analysis.
METHODS:CAC was induced in BALB/c mice using azoxymethane (AOM) and dextran sulfate sodium (DSS), and QFG was administered orally to the treatment group. The effects of QFG on CAC were evaluated using disease index, histology, and serum T-cell ratios. RNA-seq and 16S rRNA analysis assessed the transcriptome and microbiome change. Key pharmacodynamic pathways were identified by integrating these data and confirmed via Western blotting and immunofluorescence. The link between microbiota and CAC-related markers was explored using linear discriminant analysis effect size and Spearman correlation analysis.
RESULTS:Long-term treatment with QFG prevented AOM/DSS-induced CAC formation, reduced levels of interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), IL-6, and interferon γ (IFN-γ), and increased CD3⁺ and CD4⁺/CD8⁺ T cells ratio, without causing hepatic or renal toxicity. A 16S rRNA analysis revealed that QFG rebalanced the Firmicutes/Bacteroidetes ratio and mitigated AOM/DSS-induced microbiota disturbances. Transcriptomics and Western blotting analysis identified the nucleotide-binding oligomerization domain-containing protein 2 (NOD2)/nuclear factor kappa-B (NF-κB) pathway as key for QFG's treatment against CAC. Furthermore, QFG decreased the abundance of Bacilli, Bacillales, Staphylococcaceae, Staphylococcus, Lactobacillales, Aerococcus, Alloprevotella, and Akkermansia, while increasing Clostridiales, Lachnospiraceae, Lachnospiraceae_NK4A136_group, Ruminococcaceae, and Muribaculaceae, which were highly correlated with CAC-related markers or NOD2/NF-κB pathway.
CONCLUSION:By mapping the relationships between CAC, immune responses, microbiota, and key pathways, this study clarifies the mechanism of QFG in inhibiting CAC, highlighting its potential for clinical use as preventive therapy.