American Ginseng Attenuates Colitis-Associated Colon Carcinogenesis in Mice: Impact on Gut Microbiota and Metabolomics
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Chong-Zhi Wang1, Chunhao Yu2, Xiao-Dong Wen3
1Tang Center for Herbal Medicine Research, University of Chicago, Chicago, Illinois. Department of Anesthesia & Critical Care, University of Chicago, Chicago, Illinois.
Abstract:
Inflammatory bowel disease is a risk factor for colorectal cancer initiation and development. In this study, the effects of American ginseng on chemically induced colitis and colon carcinogenesis were evaluated using an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model. During the acute phase on day 15, the oral administration of ginseng (15 and 30 mg/kg/day) significantly suppressed AOM/DSS-induced colitis, as demonstrated by the disease activity index and colon tissue histology. During the chronic phase in week 13, AOM/DSS-induced tumor multiplicity was significantly suppressed by ginseng. Ginseng significantly attenuated the increase of inflammatory cytokines, such as IL1α, IL1β, IL6, G-CSF, and GM-CSF. Serum metabolomics data in the PCA plots showed good separation between the AOM/DSS model and ginseng-treated mice, and the most important endogenous metabolite changes were identified. The 16S rRNA data showed that after AOM/DSS, the microbiome community in the model group was obviously changed, and ginseng inhibited these changes. Fecal metabolomics analysis supported these findings. In conclusion, oral ginseng significantly decreased AOM/DSS-induced colitis and colon carcinogenesis by inhibiting inflammatory cytokines and restoring the metabolomics and microbiota profiles accordingly. Selective endogenous small molecules could be used as biomarkers to elucidate the effects of ginseng treatment. Cancer Prev Res; 9(10); 803-11. ©2016 AACR.
Insights
American ginseng significantly reduced colitis and colon cancer in a mouse model by lowering inflammation and restoring gut bacteria. This suggests ginseng may be a potential therapeutic agent for inflammatory bowel disease and colorectal cancer prevention.
Area of Science:
- Gastroenterology and Oncology
- Natural Product Chemistry
- Microbiome Research
Background:
- Inflammatory bowel disease (IBD) is a significant risk factor for colorectal cancer (CRC) development.
- Investigating natural compounds for chemoprevention is crucial for managing IBD-associated CRC.
- American ginseng is a traditional remedy with potential anti-inflammatory and anti-cancer properties.
Purpose of the Study:
- To evaluate the efficacy of American ginseng in preventing colitis and colon carcinogenesis.
- To investigate the molecular mechanisms underlying ginseng's effects on inflammation, metabolomics, and the gut microbiome.
Main Methods:
- Utilized a chemically induced mouse model (azoxymethane/dextran sulfate sodium) for colitis and colon carcinogenesis.
- Administered American ginseng orally at different doses (15 and 30 mg/kg/day).
- Assessed disease activity, colon histology, inflammatory cytokine levels, serum and fecal metabolomics, and gut microbiome composition (16S rRNA sequencing).
Main Results:
- Ginseng significantly suppressed chemically induced colitis and reduced colon tumor multiplicity.
- Ginseng attenuated key inflammatory cytokines (IL1α, IL1β, IL6, G-CSF, GM-CSF).
- Ginseng modulated serum and fecal metabolomics profiles and inhibited AOM/DSS-induced alterations in the gut microbiome.
Conclusions:
- Oral administration of American ginseng effectively reduces colitis and colon carcinogenesis in a preclinical model.
- Ginseng exerts its protective effects by modulating inflammatory responses and restoring metabolic and microbial homeostasis.
- Specific endogenous metabolites identified may serve as biomarkers for ginseng's therapeutic effects.
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