LAUSR

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.