Journal
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Volume 43, Issue -, Pages 107-115Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2017.02.005
Keywords
Pomegranate; Rat; Colitis; HIF1 alpha; miR-145
Funding
- Vegetable & Fruit Improvement Center, Texas A&M University, College Station, TX, USA
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This study investigated the potential role of the p70S6K1/HIFl alpha axis in the anti-inflammatory activities of pomegranate (Punica granatum L.) polyphenolics in dextran sodium sulfate (DSS)-induced colitis in Sprague-Dawley rats and in lipopolysaccharide (LPS)-treated CCD-18Co colon-myofibroblastic cells. Rats were administered either control (CT) or pomegranate beverage (PG), containing ellagic acid and ellagitannins, then exposed to three cycles of 3% DSS followed by a 2 -week recovery period. PG protected against DSS-induced colon inflammation and ulceration (50% and 66.7%, P=.05 and.045, respectively), and decreased the Ki-67 proliferative index in the central and basal regions compared to the control. PG also significantly reduced the expression of proinflammatory cytokines (TNE-alpha and IL-1 beta), COX-2, and iNOS at mRNA and protein levels. In addition, the expression of p70S6K1 and HIF1a was reduced, while the tumor suppressor miR-145 was induced by PG. The intestinal microbiota of rats treated with PG showed a significant increase in Ruminococcaceae that include several butyrate producing bacteria (P=.03). In vitro, PG reduced the expression of p70S6K1 and HIF1 alpha and induced miR-145 in a dose-dependent manner. The involvement of miR-145/p70S6K1 was confirmed by treating LPS-treated CCD-18Co cells with miR-145 antagomiR, where the pomegranate polyphenolics reversed the effects of the antagomiR for p70S6K1 mRNA and protein levels. These results suggest that pomegranate polyphenols attenuated DSS-induced colitis by modulating the miR-145/p70S6K/HIFl alpha axis, indicating potential use in therapeutic treatment of ulcerative colitis. (C) 2017 Elsevier Inc. All rights reserved.
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