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

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.