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.

Targeting NF-κB pathway for treating ulcerative colitis: comprehensive regulatory characteristics of Chinese medicines

“…Study has showed that mango (Mangifera Indica L.) extract (10 mg GAE/L) treatment is against DSSinduced colonic inflammation and decrease NF-κB and iNOS mRNA levels, as well as NF-κB and p-NF-κB protein levels in rats. In addition, mango polyphenolics treatment attenuates the levels of inflammatory markers via suppression of the PI3K/AKT/mTOR signaling pathway, in part through up-regulation of miRNA-126 in DSS-induced colonic inflammation [125].…”

Comparison of anti‐inflammatory mechanisms of mango (Mangifera Indica L.) and pomegranate (Punica Granatum L.) in a preclinical model of colitis

“…Caloric intake was calculated on the basis of 3 kcal/g of pellet and 0.612 kcal/mL of juice. a) Reproduced with slight modification from [31]. * The values are statistically significant compared to the control at p < 0.05.…”

“…Mango beverage reduced the inflammation score by Values are the mean ± SEM (n = 10 per group). a) Reproduced with slight modification from [31]. * The values are statistically significant compared to the control at p < 0.05.…”

Body Mass Index as a Determinant of Systemic Exposure to Gallotannin Metabolites during 6‐Week Consumption of Mango (Mangifera indica L.) and Modulation of Intestinal Microbiota in Lean and Obese Individuals

“…Mango is rich in gallotannins of different degrees of polymerization, gallic acid, and glucosides . Polyphenols from mango extracts exert anti‐cancer, anti‐inflammatory, and anti‐obesogenic effects in vitro and in animal models . In a human clinical trial, obese individuals that consumed freeze‐dried mango pulp for 12 weeks exhibited improved fasting blood glucose levels, suggesting potential health benefits for individuals with metabolic disorders.…”