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

Abstract

Scope Tannin-rich fruits have been evaluated as alternative prevention strategies for colorectal cancer based on their anti-inflammatory properties. This study compared tannin-rich preparations from mango (rich in gallotannins) and pomegranate (rich in ellagitannins) in the dextran sodium sulfate-induced colitis model. Methods and results In rats, mango and pomegranate beverages decreased intestinal inflammation and the levels of pro-inflammatory cytokines in mucosa and serum. The mango beverage suppressed the ratio of phosphorylated/total protein expression of the IGF-1R-AKT/mTOR axis and down-regulated mRNA expression of Igf1, Insr, and pik3cv. Pomegranate decreased p70S6K and RPS6, as well as Rps6ka2, Map2k2, and Mapk1 mRNA. In silico modeling indicated a high binding-docked of gallic acid to the catalytic domain of IGF-1R, which may suppress the activity of the enzyme. Ellagic acid docked effectively into the catalytic domains of both IGF-1R and EGFR. In vitro assays with lipopolysaccharide-treated CCD-18Co cells using polyphenolic extracts from each beverage, as well as pure compounds, corroborated the predictions made in silico. Conclusion Mango polyphenols inhibited the IGF-1R- AKT/mTOR axis, and pomegranate polyphenols downregulate the mTOR downstream pathway through reductions in ERK1/2. These results suggest that extracts rich in gallo- and ellagitannins act on different molecular targets in the protection against ulcerative colitis.

Pomegranate peel extract alters the microbiome in mice and dysbiosis caused by Citrobacter rodentium infection

“…Pomegranate peel extract and their principle components punicalagin, ellagic acid, and their metabolites, including urolithin A, have been reported to have antidiabetic, hypolipidemic, antibacterial, and antiparasitic actions (Al-Mathal & Alsalem, 2012;Finegold, Summanen, Corbett, & Downes, 2014;Howell & D'Souza, 2013;John, Bhagwat, & Luthria, 2017;Mahadwar, Chauhan, Bhagavathy, & Murphy, 2015;Salwe, Sachdev, Bahurupi, & Kumarappan, 2015). Furthermore, it has been reported to reduce the severity of DSS-and trinitrobenzene sulfonic acid-induced colitis (Kim, Banerjee, Ivanov, & Pfent, 2016;Larrosa et al, 2010;Rosillo et al, 2012).…”

Antiinflammatory and anti‐cancer activities of pomegranate and its constituent, ellagic acid: Evidence from cellular, animal, and clinical studies

“…They showed that pomegranate beverages (204 mg GAE/rat) reduce the intestinal inflammation as well as IL‐6, IL‐1β, IFN‐γ, and TNF‐α levels in both serum and mucosa. Pomegranate beverages also diminished the ribosomal protein S6 (RPS6), ribosomal protein S6 kinase A2 (RPS6KA2), mitogen‐activated protein kinase kinase 2 (MAP2K2), and mitogen‐activated protein kinase 1 (MAPK1) mRNA expression (Kim et al, ). In another study, the antiinflammatory properties of pomegranate beverage (2504.74 GAE/L), containing EA and ellagitannins, were demonstrated against DSS‐induced colon inflammation and ulceration in rats.…”

Multifaceted Healthy Benefits of <em>Mangifera Indica</em> L. (Mango): The Inestimable Value of an Orchard Recently Rooted in Sicilian Rural Areas

“…These effects can be related to the ability of mango stem bark extract to inhibit NF-κB [20]. Furthermore, Kim et al [21] reported that mango beverage, a mango pulp extract rich in polyphenols (475.90 mg/L gallic acid equivalent), reduced the inflammatory response associated with DSS-induced colitis in mice by inhibiting the IGF1R/AKT/mTOR pathway. Such an effect was attributed to gallic acid, the most prevalent polyphenol of mango pulp, which showed in silico modeling the ability to bind and inhibit the catalytic domain of IGF-1R [21].…”

“…Furthermore, Kim et al [21] reported that mango beverage, a mango pulp extract rich in polyphenols (475.90 mg/L gallic acid equivalent), reduced the inflammatory response associated with DSS-induced colitis in mice by inhibiting the IGF1R/AKT/mTOR pathway. Such an effect was attributed to gallic acid, the most prevalent polyphenol of mango pulp, which showed in silico modeling the ability to bind and inhibit the catalytic domain of IGF-1R [21]. In another study the same authors also showed that inhibition of mTOR pathway by mango polyphenols is in part due to the increased expression of miR-126, an inhibitor of the phosphatidylinositol 3-kinase (PI3K), an upstream activator of mTOR [22].…”