Mango polyphenolics reduce inflammation in intestinal colitis-involvement of the miR-126/PI3K/AKT/mTOR axis in vitro and in vivo.

Abstract

This study sought to elucidate the mechanisms underlying the anti-inflammatory effect of mango (Mangifera Indica L.) polyphenolics containing gallic acid and gallotanins, and the role of the miR-126/PI3K/AKT/mTOR signaling axis in vitro and in vivo. Polyphenolics extracted from mango (var. Keitt) were investigated in lipopolysaccharide (LPS)-treated CCD-18Co cells. Rats received either a beverage with mango polyphenolics or a control beverage, and were exposed to three cycles of 3% dextran sodium sulfate (DSS) followed by a 2-wk recovery period. The mango extract (10 mg GAE/L) suppressed the protein expression of NF-κB, p-NF-κB, PI3K (p85β), HIF-1α, p70S6K1, and RPS6 in LPS-treated CCD-18Co cells. LPS reduced miR-126 expression, whereas, the mango extract induced miR-126 expression in a dose-dependent manner. The relationship between miR-126 and its target, PI3K (p85β), was confirmed by treating cells with miR-126 antagomiR where mango polyphenols reversed the effects of the antagomiR. In vivo, mango beverage protected against DSS-induced colonic inflammation (47%, P = 0.05) and decreased the Ki-67 labeling index in the central and basal regions compared to the control. Mango beverage significantly attenuated the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and iNOS at the mRNA and protein level. Moreover, the expression of PI3K, AKT, and mTOR was reduced, whereas, miR-126 was upregulated by the mango treatment. These results suggest that mango polyphenols attenuated inflammatory response by modulating the PI3K/AKT/mTOR pathway at least in part through upregulation of miRNA-126 expression both in vitro and in vivo; thus, mango polyphenolics might be relevant as preventive agents in ulcerative colitis. © 2016 Wiley Periodicals, Inc.