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Open AccessArticle

Bioactive Polyphenols from Pomegranate Juice Reduce 5-Fluorouracil-Induced Intestinal Mucositis in Intestinal Epithelial Cells

1
Department of Pharmacy, University of Salerno, I-84084 Salerno, Italy
2
PhD Program in Drug Discovery and Development, University of Salerno, I-84084 Salerno, Italy
3
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), University of Palermo, I-90128 Palermo, Italy
4
Department of Biomedical Sciences, Cornell University, Veterinary Research Tower, Ithaca, NY 14853-6401, USA
5
European Biomedical Research Institute of Salerno, I-84125 Salerno, Italy
*
Authors to whom correspondence should be addressed.
S.M. and P.C. equally contributed as last authors.
Antioxidants 2020, 9(8), 699; https://doi.org/10.3390/antiox9080699
Received: 29 June 2020 / Revised: 26 July 2020 / Accepted: 27 July 2020 / Published: 3 August 2020
Intestinal epithelial cells (IECs) play a pivotal role in maintaining intestinal homeostasis. Different noxious agents, among them also anticancer therapies, can impair intestinal epithelial integrity triggering inflammation and oxidative stress. A frequent complication of chemotherapy is gastrointestinal mucositis, strongly influencing the effectiveness of therapy, increasing healthcare costs, and impairing patients’ quality of life. Different strategies are used to treat gastrointestinal mucositis, including products from natural sources. Our study focused on the effect of pomegranate (Punica granatum L.) juice extract on IEC-6 cells, both during inflammatory conditions and following treatment with 5-fluorouracil (5-FU). The polyphenolic profile of pomegranate juice was characterized in detail by Online Comprehensive two dimensional Liquid Chromatography-Mass Spectrometry. The evaluation of pomegranate juice extract in IEC-6 indicates a significant inhibition in proinflammatory factors, such as cytokines release, cyclooxygenase-2 and inducible nitric oxide synthase expression, and nitrotyrosine formation. Pomegranate also inhibited oxidative stress and adhesion protein expression. In 5-FU-treated IEC-6, pomegranate also inhibited both inflammatory and oxidative stress parameters and apoptosis. It promoted wound repair and tight junction expression. These results suggest a potential use of pomegranate as an adjuvant in the treatment of intestinal inflammatory and oxidative stress states, which also occur during chemotherapy-induced mucositis. View Full-Text
Keywords: intestinal epithelial cells; Punica granatum L.; inflammation; oxidative stress; 5-fluorouracil; gastrointestinal mucositis; polyphenols; onconutraceutical intestinal epithelial cells; Punica granatum L.; inflammation; oxidative stress; 5-fluorouracil; gastrointestinal mucositis; polyphenols; onconutraceutical
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Pepe, G.; Rapa, S.F.; Salviati, E.; Bertamino, A.; Auriemma, G.; Cascioferro, S.; Autore, G.; Quaroni, A.; Campiglia, P.; Marzocco, S. Bioactive Polyphenols from Pomegranate Juice Reduce 5-Fluorouracil-Induced Intestinal Mucositis in Intestinal Epithelial Cells. Antioxidants 2020, 9, 699.

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