title: The chalcone compound isosalipurposide (ISPP) exerts a cytoprotective effect against oxidative injury via Nrf2 activation.
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)-δ 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.
authors.affiliation: College of Pharmacy, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Jae Yun
authors.initials: JY
authors.lastname: Han
authors.affiliation: College of Pharmacy, Mokpo National University, Muan, Jeonnam 535-729, Republic of Korea.
authors.forename: Seung Sik
authors.initials: SS
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Yang
authors.affiliation: College of Pharmacy, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Kyu Min
authors.initials: KM
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Jang
authors.affiliation: College of Pharmacy, Mokpo National University, Muan, Jeonnam 535-729, Republic of Korea.
authors.forename: Da Eon
authors.initials: DE
authors.lastname: Park
authors.affiliation: Graduate School of Clinical Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Joon Seok
authors.initials: JS
authors.lastname: Bang
authors.affiliation: College of Pharmacy, Pusan National University, Busan, Republic of Korea.
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Jung
authors.affiliation: College of Pharmacy, Chosun University, Gwangju 501-759, Republic of Korea. Electronic address: shki@chosun.ac.kr.
authors.forename: Sung Hwan
authors.initials: SH
authors.lastname: Ki
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D061745:Antioxidant Response Elements; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008813:Mice, Inbred ICR; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
chemical_list: D000975:Antioxidants; D047188:Chalcones; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C495636:Nfe2l2 protein, mouse; C027321:isosalipurposide; D048049:Extracellular Signal-Regulated MAP Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMPK; ERK; Hepatocyte; Isosalipurposide; Nrf2; Oxidative stress