Paeonin extracted from potatoes protects gastric epithelial cells from H2O2-induced oxidative damage in vitro by PI3K/Akt-mediated Nrf2 signaling pathway

Jiping Xiao,Lijuan Yang,Bo Chen,Huachun Guo,Qiong Wang

doi:10.1038/s41598-018-28772-5

Jiping Xiao, Lijuan Yang + Show 3 more

Open Access

https://doi.org/10.1038/s41598-018-28772-5

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Abstract

In this study, it is aimed to investigate the antioxidant mechanism of new extracts from potatoes. Four pigments, namely, Petunin, Paeonin, Malvidin and Pelargonidin, were extracted from potatoes by high performance liquid chromatography (HPLC). Our results showed that the cellular morphology and cell viability were significantly altered in gastric mucosal epithelial cells (GES-1) treated with different hydrogen peroxide (H2O2) concentrations over time (P < 0.05). Paeonin presented the strongest anti-oxidative effects on H2O2-treated cells, in both a dose- and time-dependent manner, determined by ARE-luciferase activity and HO-1 mRNA expression. After pre-treatment with Paeonin in H2O2-exposed cells, Keap1, Nrf2, HO-1 and NQO1 protein expressions were remarkably up-regulated. Furthermore, immunostaining of Nrf2 expression was obviously elevated in the H2O2 + Paeonin group over time. The GSH content in the H2O2 + Paeonin group was notably lower than that in the H2O2 + Paeonin + GSK690693 group. Paeonin promoted cell cycle with augmented Cyclin D1 and p27 protein expressions. Moreover, Paeonin suppressed apoptosis with increased Bcl2, total Caspase3 and total Caspase8 protein expressions and decreased Bax, p-Caspase3 and p-Caspase8 protein expression in H2O2-treated cells. These results suggested that Paeonin might exert an anti-oxidative role by activating Nrf2 signaling pathway with the changes of cell cycle and apoptosis.

Highlights

Gastric diseases, including chronic gastritis, adenocarcinoma, duodenal and gastric ulceration and gastric mucosa-associated lymphoid tissue lymphoma, pose great financial burden on the healthcare system and significantly diminish quality of life[1,2]
Evaluations of cell cycle and apoptosis were detected by flow cytometry and Western blotting (WB)
Our data demonstrated that Paeonin treatment could remarkably ameliorate the impacts of H2O2 in cell cycle arrest and apoptosis of GES-1 cells

Summary

Introduction

Gastric diseases, including chronic gastritis, adenocarcinoma, duodenal and gastric ulceration and gastric mucosa-associated lymphoid tissue lymphoma, pose great financial burden on the healthcare system and significantly diminish quality of life[1,2]. ROS produced by mammalian cells can be degraded effectively by anti-oxidant defense molecules, such as glutathione, superoxide dismutase, catalase, peroxidase, and thioredoxin protein[6,7]. Nuclear factor-E2-related factor-2 (Nrf-2)/anti-oxidant response element (ARE) signaling pathway, which could control the expression of genes whose protein products are involved in the detoxification and elimination of reactive oxidants, is a major mechanism in the cellular defense against oxidative stress[15]. In the current study, we attempted to explore the anti-oxidative roles of the ingredients or extracts from potatoes that can suppress oxidative stress damages, and to further investigate the underlying mechanisms implicated in Nrf2/ARE signaling pathway of these materials in inhibiting oxidative stress injuries

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