Hyemee Kim1, Nivedita Banerjee2, Ivan Ivanov3, Catherine M Pfent4, Kalan R Prudhomme5, William H Bisson5, Roderick H Dashwood1,6, Stephen T Talcott1, Susanne U Mertens-Talcott7,8. 1. Department of Nutrition and Food Science, Texas A&M University, College Station, TX, USA. 2. Interdisciplinary Program of Toxicology, Texas A&M University, College Station, TX, USA. 3. Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA. 4. Department of Veterinary Pathobiology, Texas A&M University, College Station, TX, USA. 5. Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, USA. 6. Center for Epigenetics & Disease Prevention, Texas A&M Health Science Center, Houston, TX, USA. 7. Department of Nutrition and Food Science, Texas A&M University, College Station, TX, USA. smtalcott@tamu.edu. 8. Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA. smtalcott@tamu.edu.
Abstract
SCOPE: Tannin-rich fruits have been evaluated as alternative prevention strategies for colorectal cancer based on their anti-inflammatory properties. This study compared tannin-rich preparations from mango (rich in gallotannins) and pomegranate (rich in ellagitannins) in the dextran sodium sulfate-induced colitis model. METHODS AND RESULTS: In rats, mango and pomegranate beverages decreased intestinal inflammation and the levels of pro-inflammatory cytokines in mucosa and serum. The mango beverage suppressed the ratio of phosphorylated/total protein expression of the IGF-1R-AKT/mTOR axis and downregulated mRNA expression of Igf1, Insr, and pik3cv. Pomegranate decreased p70S6K and RPS6, as well as Rps6ka2, Map2k2, and Mapk1 mRNA. In silico modeling indicated a high binding of docked of gallic acid to the catalytic domain of IGF-1R, which may suppress the activity of the enzyme. Ellagic acid docked effectively into the catalytic domains of both IGF-1R and EGFR. In vitro assays with lipopolysaccharide-treated CCD-18Co cells using polyphenolic extracts from each beverage, as well as pure compounds, corroborated the predictions made in silico. CONCLUSION: Mango polyphenols inhibited the IGF-1R- AKT/mTOR axis, and pomegranate polyphenols downregulate the mTOR downstream pathway through reductions in ERK1/2. These results suggest that extracts rich in gallo- and ellagitannins act on different molecular targets in the protection against ulcerative colitis.
SCOPE: Tannin-rich fruits have been evaluated as alternative prevention strategies for n class="Disease">colorectal cancer based on their anti-inflammatory properties. This study compared tannin-rich preparations from mango (rich in gallotannins) and pomegranate (rich in ellagitannins) in the dextran sodium sulfate-induced colitis model. METHODS AND RESULTS: In rats, mango and pomegranate beverages decreased intestinal inflammation and the levels of pro-inflammatory cytokines in mucosa and serum. The mango beverage suppressed the ratio of phosphorylated/total protein expression of the IGF-1R-AKT/mTOR axis and downregulated mRNA expression of Igf1, Insr, and pik3cv. Pomegranate decreased p70S6K and RPS6, as well as Rps6ka2, Map2k2, and Mapk1 mRNA. In silico modeling indicated a high binding of docked of gallic acid to the catalytic domain of IGF-1R, which may suppress the activity of the enzyme. Ellagic acid docked effectively into the catalytic domains of both IGF-1R and EGFR. In vitro assays with lipopolysaccharide-treated CCD-18Co cells using polyphenolic extracts from each beverage, as well as pure compounds, corroborated the predictions made in silico. CONCLUSION:Mangopolyphenols inhibited the IGF-1R- AKT/mTOR axis, and pomegranatepolyphenols downregulate the mTOR downstream pathway through reductions in ERK1/2. These results suggest that extracts rich in gallo- and ellagitannins act on different molecular targets in the protection against ulcerative colitis.
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