Pomegranate polyphenolics reduce inflammation and ulceration in intestinal colitis-involvement of the miR-145/p70S6K1/HIF1 axis in vivo and in vitro.
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abstract
This study investigated the potential role of the p70S6K1/HIF1 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 (TNF- and IL-1), COX-2, and iNOS at mRNA and protein levels. In addition, the expression of p70S6K1 and HIF1 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 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/HIF1 axis, indicating potential use in therapeutic treatment of ulcerative colitis.
Kim, H., Banerjee, N., Sirven, M. A., Minamoto, Y., Markel, M. E., Suchodolski, J. S., Talcott, S. T., & Mertens-Talcott, S. U.
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Kim, Hyemee||Banerjee, Nivedita||Sirven, Maritza A||Minamoto, Yasushi||Markel, Melissa E||Suchodolski, Jan S||Talcott, Stephen T||Mertens-Talcott, Susanne U
