The chalcone compound isosalipurposide (ISPP) exerts a cytoprotective effect against oxidative injury via Nrf2 activation
- Authors
- Han, Jae Yun; Cho, Seung Sik; Yang, Ji Hye; Kim, Kyu Min; Jang, Chang Ho; Park, Da Eon; Bang, Joon Seok; Jung, Young Suk; Ki, Sung Hwan
- Issue Date
- Aug-2015
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- Isosalipurposide; Nrf2; Oxidative stress; Hepatocyte; ERK; AMPK
- Citation
- TOXICOLOGY AND APPLIED PHARMACOLOGY, v.287, no.1, pp 77 - 85
- Pages
- 9
- Journal Title
- TOXICOLOGY AND APPLIED PHARMACOLOGY
- Volume
- 287
- Number
- 1
- Start Page
- 77
- End Page
- 85
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/10471
- DOI
- 10.1016/j.taap.2015.05.015
- ISSN
- 0041-008X
1096-0333
- Abstract
- The chalcone compound isosalipurposide (ISPP) has been successfully isolated from the native Korean plant species Corylopsis coreana Uyeki (Korean winter hazel). However, the therapeutic efficacy of ISPP remains poorly understood. This study investigated whether ISPP has the capacity to activate NF-E2-related factor (Nrf2)-antioxidant response element (ARE) signaling and induce its target gene expression, and to determined the protective role of ISPP against oxidative injury of hepatocytes. In HepG2 cells, nuclear translocation of Nrf2 is augmented by ISPP treatment. Consistently, ISPP increased ARE reporter gene activity and the protein levels of glutamate cysteine ligase (GCL) and hemeoxygenase (HO-1), resulting in increased intracellular glutathione levels. Cells pretreated with ISPP were rescued from tert-butylhydroperoxide-induced reactive oxygen species (ROS) production and glutathione depletion and consequently, apoptotic cell death. Moreover, ISPP ameliorated the mitochondrial dysfunction and apoptosis induced by rotenone which is an inhibitor of complex 1 of the mitochondrial respiratory chain. The specific role of Nrf2 activation by ISPP was demonstrated using an ARE-deletion mutant plasmid and Nrf2-knockout cells. Finally, we observed that extracellular signal-regulated kinase (ERK) and AMP-activated protein kinase (AMPK), but not protein kinase C (PKC)-delta or other mitogen-activated protein kinases (MAPKs), are involved in the activation of Nrf2 by ISPP. Taken together, our results demonstrate that ISPP has a cytoprotective effect against oxidative damage mediated through Nrf2 activation and induction of its target gene expression in hepatocytes. (C) 2015 Elsevier Inc All rights reserved.
- Files in This Item
-
Go to Link
- Appears in
Collections - 약학대학 > 약학부 > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.