Ellagic Acid Alleviates Diquat-Induced Jejunum Oxidative Stress in C57BL/6 Mice through Activating Nrf2 Mediated Signaling Pathway.

Xiangyu Zhang,Junjun Wang,Yujun Wu,Dandan Han,Xiaoyi Liu,Shilan Wang

doi:10.3390/nu14051103

Abstract

Ellagic acid (EA) is the main constituent found in pomegranate rind, which has anti-inflammatory and antioxidant effects. However, whether EA can alleviate diquat-induced oxidative stress is still unknown. Here, the effects and mechanisms of EA on jejunum oxidative stress induced by diquat was investigated. Oxidative stress was induced in mice by administrating diquat (25 mg/kg body weight) followed by treatment with 100 mg/kg body weight EA for 5 days. Results showed that oral administration of EA significantly ameliorated diquat-induced weight loss and oxidative stress (p < 0.05) evidenced by reduced ROS production in the jejunum. Furthermore, EA up-regulated the mRNA expression of the antioxidant enzymes (Nrf2, GPX1 and HO-1) when mice were challenged with diquat, compared with the diquat group (p < 0.05). Importantly, pharmacological inhibition of Nrf2 by ML385 counteracted the EA-mediated alleviation of jejunum oxidative stress, as evidence by body weight and ROS production. Also, immunohistochemistry staining confirmed the markedly decreased jejunal Nrf2 expression. The up-regulated effect on NQO1 and HO-1 mRNA expression induced by EA was diminished in mice treated with ML385 (p < 0.05). Together, our results demonstrated that therapeutic and preventative EA treatment was effective in reducing weight loss and oxidative stress induced by diquat through the Nrf2 mediated signaling pathway.

Highlights

Reactive oxygen species (ROS) accumulation and oxidative stress are important causes of many diseases [1,2]
Ellagic acid (EA) treatment alleviated intestinal villi damage caused by diquat (Figure 1C) and reduced the ROS content in the jejunum (Figure 1G)
The results demonstrated that EA supplementation can improve diquat-induced oxidative stress, and this effect is achieved through the Nuclear factor erythroid 2-related factor 2 (Nrf2) mediated signaling pathway

Summary

Introduction

Reactive oxygen species (ROS) accumulation and oxidative stress are important causes of many diseases [1,2]. The production of oxidants and antioxidants in biological systems is balanced. When the body’s antioxidant defense system fails to eliminate excessive ROS production, tissues such as intestinal tissue will suffer from oxidative damage [3]. As the main place for nutrient digestion and absorption, the intestine is important for the growth and development of the body. Because the intestine is located at the junction of the body and its lumen environment, it is more vulnerable to oxidative damage, which has adverse effects on the body [4–6]. Some studies have confirmed that excessive ROS accumulation in the intestine can damage the morphology of intestinal villi, increase intestinal mucosal permeability, and is associated with reduced life expectancy [7,8]

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