Apple peel polyphenols: a key player in the prevention and treatment of experimental inflammatory bowel disease.

Diets rich in fruits and vegetables may reduce oxidative stress (OxS) and inflammation via several mechanisms. These beneficial effects may be due to their high polyphenol content. The aims of the present study are to evaluate the preventive and therapeutic aspects of polyphenols in dried apple peel powder (DAPP) on intestinal inflammation while elucidating the underlying mechanisms and clinical benefits. Induction of intestinal inflammation in mice was performed by oral administration of the inflammatory agent dextran sulfate sodium (DSS) at 2.5% for 10 days. Physiological and supraphysiological doses of DAPP (200 and 400 mg/kg/day respectively) were administered by gavage for 10 days pre- and post-DSS treatment. DSS-mediated inflammation caused weight loss, shortening of the colon, dystrophic detachment of the epithelium, and infiltration of mono- and poly-morphonuclear cells in the colon. DSS induced an increase in lipid peroxidation, a down-regulation of antioxidant enzymes, an augmented expression of myeloperoxidase (MPO) and cyclooxygenase-2 (COX-2), an elevated production of prostaglandin E2 (PGE2) and a shift in mucosa-associated microbial composition. However, DAPP normalized most of these abnormalities in preventive or therapeutic situations in addition to lowering inflammatory cytokines while stimulating antioxidant transcription factors and modulating other potential healing pathways. The supraphysiological dose of DAPP in therapeutic situations also improved mitochondrial dysfunction. Relative abundance of Peptostreptococcaceae and Enterobacteriaceae bacteria was slightly decreased in DAPP-treated mice. In conclusion, DAPP exhibits powerful antioxidant and anti-inflammatory action in the intestine and is associated with the regulation of cellular signalling pathways and changes in microbiota composition. Evaluation of preventive and therapeutic effects of DAPP may be clinically feasible in individuals with intestinal inflammatory bowel diseases.

Apple peel polyphenols reduce mitochondrial dysfunction in mice with DSS-induced ulcerative colitis.

Inflammatory bowel diseases (IBDs) are multifaceted and relapsing immune disorders, which necessitate long-term dependence on powerful drugs. As the use of natural product-based therapies has emerged as a promising intervention, the present study aimed to further characterize dried apple peel powder (DAPP) mechanisms of action and evaluate the preventive and curative effects of DAPP on mitochondrial functions in a murine model. Induction of intestinal inflammation in mice is performed by oral administration of the dextran sodium sulfate (DSS) at 2.5% for 10 days. Doses of DAPP (200 or 400 mg/kg/day) were administered by gavage for 10 days pre- and 1 day after colitis induction simultaneously with DSS treatment for a period of 10 days. The preventive (200 mg/kg/day) and therapeutic (400 mg/kg/day) doses of DAPP limited DSS-induced histological lesions, improved macroscopic parameters and attenuated clinical signs. DAPP at the same conditions reduced massive infiltration of inflammatory cells and concomitantly displayed a robust potential of counteracting inflammation and oxidative stress in DSS mice. Moreover, DAPP partially restored mitochondrial abnormalities related to size, density, redox homeostasis, fatty acid ß-oxidation, ATP synthesis, apoptosis and regulatory mitochondrial transcription factors. Our findings demonstrate the preventive and therapeutic impact of DAPP on experimental colitis while underlying the role of mitochondria. They also suggest that this natural DAPP product may represent an interesting candidate for further studies on the prevention/treatment of IBD.