Apple peel polyphenols and their beneficial actions on oxidative stress and inflammation.
Since gastrointestinal mucosa is constantly exposed to reactive oxygen species from various sources, the presence of antioxidants may contribute to the body's natural defenses against inflammatory diseases.


OBJECTIVE
To define the polyphenols extracted from dried apple peels (DAPP) and determine their antioxidant and anti-inflammatory potential in the intestine. Caco-2/15 cells were used to study the role of DAPP preventive actions against oxidative stress (OxS) and inflammation induced by iron-ascorbate (Fe/Asc) and lipopolysaccharide (LPS), respectively.


RESULTS
The combination of HPLC with fluorescence detection, HPLC-ESI-MS TOF and UPLC-ESI-MS/MS QQQ allowed us to characterize the phenolic compounds present in the DAPP (phenolic acids, flavonol glycosides, flavan-3-ols, procyanidins). The addition of Fe/Asc to Caco-2/15 cells induced OxS as demonstrated by the rise in malondialdehyde, depletion of n-3 polyunsaturated fatty acids, and alterations in the activity of endogenous antioxidants (SOD, GPx, G-Red). However, preincubation with DAPP prevented Fe/Asc-mediated lipid peroxidation and counteracted LPS-mediated inflammation as evidenced by the down-regulation of cytokines (TNF-α and IL-6), and prostaglandin E2. The mechanisms of action triggered by DAPP induced also a down-regulation of cyclooxygenase-2 and nuclear factor-κB, respectively. These actions were accompanied by the induction of Nrf2 (orchestrating cellular antioxidant defenses and maintaining redox homeostasis), and PGC-1α (the "master controller" of mitochondrial biogenesis).


CONCLUSIONS
Our findings provide evidence of the capacity of DAPP to reduce OxS and inflammation, two pivotal processes involved in inflammatory bowel diseases.
Research Centre, Sainte-Justine Hospital, Montreal, Quebec, Canada.
Marie Claude
MC
Denis
Alexandra
A
Furtos
Stéphanie
S
Dudonné
Alain
A
Montoudis
Carole
C
Garofalo
Yves
Y
Desjardins
Edgard
E
Delvin
Emile
E
Levy
D000975:Antioxidants / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000737:chemistry / Q000494:pharmacology; D018938:Caco-2 Cells; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005296:Ferrous Compounds / Q000737:chemistry / Q000494:pharmacology; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005980:Glutathione Reductase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D027845:Malus / Q000737:chemistry*; D008954:Models, Biological; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D059808:Polyphenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D000975:Antioxidants; D005296:Ferrous Compounds; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D059808:Polyphenols; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D001205:Ascorbic Acid