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Water Extract of Rosa laevigata Michx. Protects Hepatocytes from Arachidonic Acid and Iron-mediated Oxidative Stress

아라키돈산과 철 유도성 산화적 스트레스에 대한 금앵자(金櫻子) 열수 추출물의 간세포 보호 효능

Ko, Hae Li;Jegal, Kyung Hwan;Song, Si Yeon;Kim, Nan Ee;Kang, Jiwon;Byun, Sung Hui;Kim, Young Woo;Cho, Il Je;Kim, Sang Chan
고해리;제갈경환;송시연;김난이;강지원;변성희;김영우;조일제;김상찬

  • Received : 2015.10.13
  • Accepted : 2015.11.16
  • Published : 2015.11.30

Abstract

Objectives : Rosa laevigata Michx. has been used for the treatment of renal disease in traditional Korean medicine. In this study, we investigated cytoprotective effect of R. laevigata water extract (RLE) against oxidative stress induced by arachidonic acid (AA) + iron.Methods : To evaluate the protective effects of RLE against AA + iron-induced oxidative stress in HepG2 cell, cell viability and changes on apoptosis-related proteins were assessed by MTT and immunoblot analyses. The effects of RLE on reduced glutathione level, production of reactive oxygen species and mitochondrial membrane potential were also monitored. Furthermore, to verify underlying molecular mechanism, NF-E2-related factor 2 (Nrf2) was examined by immunoblot analysis. Additionally, Nrf2 transactivation and its downstream target genes expression were also determined by reporter gene and realtime RT-PCR analyses.Results : RLE pretreatment (30-300 μg/ml) prevented cells from AA + iron-mediated cell death in a concentration dependent manner. In addition, 100 μg/ml RLE inhibited AA + iron-induced glutathione depletion, reactive oxygen species production and mitochondrial dysfunction. RLE accumulated nuclear Nrf2 and also transactivated Nrf2, which was evidenced by antioxidant response element- and glutathione S-transferase A2-driven luciferase activities and mRNA level of glutamate-cysteine ligase catalytic subunit, NAD(P)H:quinone oxidoreductase 1 and sestrin 2. Moreover, protective effect of RLE against AA + iron was abolished in Nrf2 knockout cells.Conclusions : These results indicate that RLE has the ability to protect hepatocyte against oxidative stress through Nrf2 activation.

Keywords

Rosa laevigata Michx.;Hepatocytes protection;Oxidative stress;Nrf2

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Acknowledgement

Grant : 방제과학 글로벌 연구센터