Chrysanthemum extract attenuates hepatotoxicity via inhibiting oxidative stress in vivo and in vitro.

Zixia Tian,Xiaobin Pang,Yuezhen Jin,Chunli Wang,Guang Han,Haiyan Jia,Xinmei Xie,Minghui Wang,Xuli Rong,Jiejian Kou

doi:10.29219/fnr.v63.1667

Abstract

Background‘Bianliang ziyu’, a famous chrysanthemum variety commonly planted in Kaifeng, China, is often consumed by local residents. However, the hepatoprotective effects of Bianliang ziyu and their underlying mechanisms are not clear.ObjectiveIn this study, we investigated the hepatoprotective and antioxidative effects of Bianliang ziyu extract (BZE) on liver injury and explored its molecular mechanisms.DesignSprague-Dawley rats were administered BZE by intragastric administration for 8–9 days, and then alcohol or carbon tetrachloride (CCl4) was administered by gavage to induce acute liver injury. The activities of serum alanine aminotransferase, aspartate aminotransferase, superoxide dismutase, and malondialdehyde in the rats were measured, and the liver of each rat was examined for histopathological changes. In vitro, HL-7702 cells were pretreated with BZE for 24 h and then exposed to 30 mmol•L−1 acetaminophen (APAP) for 12 h. The survival rate of the cells and the alanine aminotransferase and aspartate aminotransferase activities were determined. Then, we investigated the effects of BZE on oxidative stress, apoptosis, and the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) signaling in HL-7702 cells induced by APAP.ResultsThe results showed that BZE prevented alcohol-, CCl4-, and APAP-induced liver injury and suppressed hepatic oxidative stress in vitro and in vivo. BZE was also observed to significantly inhibit the reduction of mitochondrial membrane potential and regulate the expression of Bcl-2, Bax and Caspase-3 in APAP-induced HL-7702 cells. In addition, BZE significantly promoted nuclear translocation and the expression of Nrf2 as well as its downstream gene hemeoxygenase-1 (HO-1) in vitro. Furthermore, the findings showed that Nrf2 siRNA reversed the effects of BZE on cell survival and apoptosis-related protein expression in APAP-induced HL-7702 cells.ConclusionsBZE plays an important role in preventing hepatotoxicity by inhibiting oxidative stress and apoptosis through activation of Nrf2 signaling. BZE could be developed as an effective functional food for protecting the liver.

Highlights

Background: ‘Bianliang ziyu’, a famous chrysanthemum variety commonly planted in Kaifeng, China, is often consumed by local residents
We investigated the effects of Bianliang ziyu extract (BZE) on oxidative stress, apoptosis, and the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) signaling in HL-7702 cells induced by APAP
Increasing evidence has shown that the Keap-1/Nrf2 signaling pathway plays a key role in maintaining cellular redox homeostasis, and it has become an important target for the prevention and treatment of oxidative stress-related diseases, including liver oxidative stress damage caused by exogenous compounds toxic to the liver [16–18]

Summary

Introduction

Background: ‘Bianliang ziyu’, a famous chrysanthemum variety commonly planted in Kaifeng, China, is often consumed by local residents. We investigated the effects of BZE on oxidative stress, apoptosis, and the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) signaling in HL-7702 cells induced by APAP. The hepatocytes that make up most of the structure of the liver are very active during the metabolism of exogenous chemicals, and the liver and concomitantly the hepatocytes are a major target of toxic substances [2] Many factors, such as alcohol, carbon tetrachloride (CCl4), tert-butyl hydroperoxide, and the excessive use of acetaminophen (APAP), can induce liver damage [3]. Increasing evidence has shown that the Keap-1/Nrf signaling pathway plays a key role in maintaining cellular redox homeostasis, and it has become an important target for the prevention and treatment of oxidative stress-related diseases, including liver oxidative stress damage caused by exogenous compounds toxic to the liver [16–18]

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