Polyphenolics from Mango (Mangifera indica L.) and Pomegranate (Punica granatum L.) Suppress Inflammation in in vivo and in vitro Models for Colitis
MetadataShow full item record
Ulcerative colitis is a chronic inflammation of the large intestine, and it may increase risk of human colorectal cancer. Polyphenolics from mango and pomegranate have been shown to have potent anti-inflammatory properties, thus they could be the potential therapeutic agents for colitis. However, the mechanism underlying these effects of polyphenolics has not yet been elucidated. To determine the anti-inflammatory effects and possible mechanisms of polyphenolics from mango (gallic acid and gallotannins), and pomegranate (ellagic acid and ellagitannins) in dextran sodium sulfate (DSS)-induced colitis in rats, Sprague Dawley rats were administered control, mango, or pomegranate juice, and were exposed to three cycles of 3% DSS followed by 2-week recovery period. Colon inflammation and injury scores were assessed, and cell proliferation was evaluated by immunohistochemical detection of Ki-67. The mRNA and protein expressions involved in the inflammatory response and the mTOR pathway were analyzed by qRT-PCR, low density arrays, western blot analysis and multiplex bead assay. The involvement of miRNAs was additionally investigated with the antagomiR-126 and antagomiR-145 in lipopolysaccharide (LPS)-treated CCD-18Co, non-cancer colon fibroblasts cell lines. Both mango and pomegranate showed anti-inflammatory properties in vitro and in vivo. Mango and pomegranate juice reduced DSS-induced colon inflammation score (41% and 50%) and cell proliferative index (38% and 36%) during chronic colitis in rats compared to control juice. Mango and pomegranate juice significantly attenuated the pro-inflammatory cytokines, CRP, TNF-alpha, IL-1beta, GM-CSF, and IL-6 levels in colonic tissues. In addition, mango and pomegranate juice suppressed COX-2 and iNOS mRNA and protein expressions. Mango juice suppressed HIF-1alpha by decreasing the PI3K(p85beta)/AKT-mTOR signaling axis via up-regulation of miR-126, while pomegranate decreased p70S6K and HIF-1alpha by up-regulating miR-145. The interactions of mango with miR-126/PI3K(p85beta) and pomegranate with miR-145/p70S6K1 were additionally identified in CCD-18Co cells, where mango and pomegranate extract reversed the effect of the antagomiR. In addition, the modulation of microbiota composition (Blautia, Fusobacterium, and Ruminococcaceae) by pomegranate and short-chain fatty acids (SCFA; Isovalerate and valerate) production by mango may be involved in at least in part the anti-inflammatory effects of polyphenolics. These results suggest that both mango and pomegranate polyphenolics seem to have potential in the prevention and mitigation of colon inflammation.
Kim, Hye Mee (2013). Polyphenolics from Mango (Mangifera indica L.) and Pomegranate (Punica granatum L.) Suppress Inflammation in in vivo and in vitro Models for Colitis. Doctoral dissertation, Texas A & M University. Available electronically from