Research Centre, Sainte-Justine Hospital, Montreal, Quebec, Canada.
PLoS One. 2013;8(1):e53725. doi: 10.1371/journal.pone.0053725. Epub 2013 Jan 23.
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.
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.
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).
Our findings provide evidence of the capacity of DAPP to reduce OxS and inflammation, two pivotal processes involved in inflammatory bowel diseases.
定义从干苹果皮中提取的多酚(DAPP),并确定其在肠道中的抗氧化和抗炎潜力。使用 Caco-2/15 细胞研究 DAPP 对铁-抗坏血酸(Fe/Asc)和脂多糖(LPS)分别诱导的氧化应激(OxS)和炎症的预防作用。
将 HPLC 与荧光检测、HPLC-ESI-MS TOF 和 UPLC-ESI-MS/MS QQQ 相结合,用于表征 DAPP 中存在的酚类化合物(酚酸、黄酮醇糖苷、黄烷-3-醇、原花青素)。将 Fe/Asc 添加到 Caco-2/15 细胞中会引起 OxS,这可以通过丙二醛的增加、n-3 多不饱和脂肪酸的消耗以及内源性抗氧化剂(SOD、GPx、G-Red)活性的改变来证明。然而,DAPP 的预孵育可防止 Fe/Asc 介导的脂质过氧化,并拮抗 LPS 介导的炎症,这可以通过下调细胞因子(TNF-α 和 IL-6)和前列腺素 E2 来证明。DAPP 触发的作用机制还分别下调了环氧合酶-2 和核因子-κB。这些作用伴随着 Nrf2(协调细胞抗氧化防御和维持氧化还原平衡)和 PGC-1α(线粒体生物发生的“主控制器”)的诱导。
我们的研究结果为 DAPP 降低 OxS 和炎症的能力提供了证据,OxS 和炎症是炎症性肠病中涉及的两个关键过程。