皂角刺 추출물의 Nrf2 활성화를 통한 간세포 보호 효과

• Published in: 大韓本草學會誌 Vol. 30; no. 4; pp. 57 - 64
• Main Authors: 김재광, 박상미, 제갈경환, 김영우, 변성희, 김상찬, 조일제, Kim, Jae Kwang, Park, Sang Mi, Jegal, Kyung Hwan, Kim, Young Woo, Byun, Sung Hui, Kim, Sang Chan, Cho, Il Je
• Format: Journal Article
• Language: Korean
• Published: 대한본초학회 01.07.2015
• Subjects: 한의학; Oxidative stress; Hepatoprotection; Gleditsia sinensis Lam; Gleditsia spina; Antioxidant gene; Nrf2
• ISSN: 1229-1765; 2288-7199

Objectives : Oxidative stress is one of the most causes of hepatocyte injury. Gleditsia spina, the thorns ofGleditsia sinensisLam., has been known for its anti-cancer and anti-inflammatory effects in Korean medicine. The present study investigated hepatoprotective effect of Gleditsia spina water extract (GSE) against oxidative stress induced by arachidonic acid (AA) + iron in HepG2 cells.Methods : To investigate cytoprotective effect of GSE, cells were pretreated with GSE and then subsequently exposed to 10 μM AA for 12 h, followed by 5 μM iron. Cell viability was monitored by MTT assay, and expression of apoptosis-related proteins was examined by immunoblot analysis. To identify responsible molecular mechanisms, reactive oxygen species (ROS) production, GSH contents, and mitochondrial membrane potential were measured. In addition, effect of GSE on nuclear factor erythroid 2-related factor 2 (Nrf2) activation was determined by immunoblot and antioxidant response element (ARE)-driven reporter gene assays.Results : GSE pretreatment prevented AA + iron-mediated cytotoxicity in concentration dependent manner. In addition, ROS production, glutathione depletion, and mitochondrial impairment by AA + iron were significantly inhibited by GSE. Furthermore, GSE promoted translocation of Nrf2 to nucleus, which acts as essential transcription factor for induction of antioxidant genes. Increased nuclear Nrf2 that caused by GSE treatment promoted transcriptional activity of ARE. Finally, GSE up-regulated sestrin-2 which was widely recognized as target gene of Nrf2.Conclusions : This study demonstrates that GSE protects hepatocytes from oxidative stress via activation of Nrf2 signaling pathway.