Protective action of pomegranate peel polyphenols in type 2 diabetic rats via the translocation of Nrf2 and FoxO1 regulated by the PI3K/Akt pathway†

IF 5.4 1区 农林科学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Food & Function Pub Date : 2021-09-23 DOI:10.1039/D1FO01213D
Weimin Zhang, Chen Hou, Lin Du, Xitong Zhang, Mi Yang, Li Chen and Jianke Li
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引用次数: 4

Abstract

The aim of this study is to investigate the protective mechanism of pomegranate peel polyphenols (PPPs) in in vivo and in vitro rat models of T2DM. Our results showed that PPPs markedly improved the symptoms of diabetes, such as insulin resistance, impaired insulin secretion, and pancreatic oxidative damage, which contributed to the attenuation of the symptoms of hyperglycemia in a high-fat diet (HFD) combined with streptozocin (STZ) induced type 2 diabetes mellitus in rats. On the one hand, PPPs promoted the translocation of Nrf2 from the cytoplasm to the nucleus, the key protein down-regulated by the PI3K/Akt pathway, activating its downstream phase 2 antioxidant enzyme system. On the other hand, the positive effect was associated with another downstream protein of the PI3K/Akt pathway, FoxO1. With the activation of Akt phosphorylation, the phosphorylated FoxO1 protein transferred from the nucleus to the cytoplasm, releasing the block of Pdx-1 and its downstream genes. The inhibitor of the PI3K/Akt pathway was also studied in INS-1 cells in order to verify the mechanism observed in vivo. Altogether, we presented evidence that PPPs activated the translocation of Nrf2 into the nucleus and resulted in increased antioxidant activity, and PPPs promoted the translocation of FoxO1 out of the nucleus resulting in an increase in insulin synthesis in vivo and in vitro. Pomegranate extracts may show great potential and application prospects as functional foods or preventive drugs to improve pancreatic beta cell dysfunction and provide a reference for future development in health care.

Abstract Image

石榴皮多酚通过PI3K/Akt通路调节的Nrf2和FoxO1易位对2型糖尿病大鼠的保护作用
本研究旨在探讨石榴皮多酚(PPPs)对体内和体外大鼠T2DM模型的保护机制。我们的研究结果表明,PPPs显著改善了糖尿病的症状,如胰岛素抵抗、胰岛素分泌受损和胰腺氧化损伤,这有助于减轻高脂肪饮食(HFD)联合链脲佐菌素(STZ)诱导的2型糖尿病大鼠的高血糖症状。PPPs一方面促进PI3K/Akt通路下调的关键蛋白Nrf2从细胞质向细胞核的易位,激活其下游2期抗氧化酶系统。另一方面,这种积极作用与PI3K/Akt通路的另一个下游蛋白FoxO1有关。随着Akt磷酸化的激活,磷酸化的FoxO1蛋白从细胞核转移到细胞质中,释放Pdx-1及其下游基因的阻滞。为了验证在体内观察到的机制,我们还在INS-1细胞中研究了PI3K/Akt通路的抑制剂。总之,我们提供的证据表明,PPPs激活Nrf2转位到细胞核中,导致抗氧化活性增加,PPPs促进fox01转位到细胞核外,导致体内和体外胰岛素合成增加。石榴提取物作为改善胰腺β细胞功能障碍的功能食品或预防药物具有很大的潜力和应用前景,为今后在保健领域的开发提供参考。
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来源期刊
Food & Function
Food & Function BIOCHEMISTRY & MOLECULAR BIOLOGY-FOOD SCIENCE & TECHNOLOGY
CiteScore
10.10
自引率
6.60%
发文量
957
审稿时长
1.8 months
期刊介绍: Food & Function provides a unique venue for physicists, chemists, biochemists, nutritionists and other food scientists to publish work at the interface of the chemistry, physics and biology of food. The journal focuses on food and the functions of food in relation to health.
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