Neohesperidin Dihydrochalcone versus CCl4-Induced Hepatic Injury through Different Mechanisms: The Implication of Free Radical Scavenging and Nrf2 Activation

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• 作者：Chuanyang Su ; Xiaomin Xia ; Qiong Shi ; Xiufang Song ; Juanli Fu ; Congxue Xiao ; Hongjun Chen ; Bin Lu ; Zhiyin Sun ; Shanmei Wu ; Siyu Yang ; Xuegang Li ; Xiaoli Ye ; Erqun Song ; Yang Song
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2015
• 出版时间：June 10, 2015
• 年：2015
• 卷：63
• 期：22
• 页码：5468-5475
• 全文大小：353K
• ISSN：1520-5118

文摘

Neohesperidin dihydrochalcone (NHDC), a sweetener derived from citrus, belongs to the family of bycyclic flavonoids dihydrochalcones. NHDC has been reported to act against CCl₄-induced hepatic injury, but its mechanism is still unclear. We first discovered that NHDC showed a strong ability to scavenge free radicals. In addition, NHDC induces the phase II antioxidant enzymes heme oxygenase 1 (HO-1) and NAD(P)H/quinone oxidoreductase 1 (NQO1) through the activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/antioxidant response element (ARE) signaling. Further assays demonstrated that NHDC induces accumulation of Nrf2 in the nucleus and augmented Nrf2-ARE binding activity. Moreover, NHDC inhibits the ubiquitination of Nrf2 and suggests the modification of Kelch-like ECH-associated protein 1 (Keap1) and the disruption of the Keap1/Nrf2 complex. c-Jun N-terminal kinase (JNK) and p38 but not extracellular signal-regulated protein kinase (ERK) phosphorylations were up-regulated by NHDC treatment. Taken together, NHDC showed its protective antioxidant effect against CCl₄-induced oxidative damage via the direct free radical scavenging and indirect Nrf2/ARE signaling pathway.