Senkyunolides reduce hydrogen peroxide-induced oxidative damage in human liver HepG2 cells via induction of heme oxygenase-1

被引:74
作者
Qi, Hongyi [1 ]
Siu, Shiu On [2 ]
Chen, Yan [3 ]
Han, Yifan [4 ]
Chu, Ivan K. [2 ]
Tong, Yao [1 ]
Lau, Allan S. Y. [5 ]
Rong, Jianhui [1 ]
机构
[1] Univ Hong Kong, Sch Chinese Med, Li Ka Shing Fac Med, Pokfulam, Hong Kong, Peoples R China
[2] Univ Hong Kong, Dept Chem, Pokfulam, Hong Kong, Peoples R China
[3] Univ Hong Kong, Dept Surg, Pokfulam, Hong Kong, Peoples R China
[4] Hong Kong Polytech Univ, Dept Appl Biol & Chem Technol, Kowloon, Hong Kong, Peoples R China
[5] Univ Hong Kong, Li Ka Shing Fac Med, Mol Chinese Med Lob, Pokfulam, Hong Kong, Peoples R China
关键词
Cytoprotection; Antioxidation; Heme oxygenase 1; Rhizoma Chuanxiong; Bioactivity-guided fractionation; LIGUSTICUM-CHUANXIONG; TRADITIONAL CHINESE; LIPID-PEROXIDATION; FORMULATION ISF-1; STRESS; CHEMOPREVENTION; INGREDIENTS; ANTIOXIDANT; EXPRESSION; MEDICINE;
D O I
10.1016/j.cbi.2009.11.029
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Rhizoma Chuanxiong is widely used as folk medicine to treat the diseases caused by oxidative stress and inflammation. To delineate the underlying molecular mechanisms, we recently found that Rhizoma Chuanxiong extract significantly induced heme oxygenase-1 (HO-1), an enzyme that degrades intracellular heme into three bioactive products: biliverdin, carbon monoxide and free iron. The anti-inflammatory, antiapoptotic and antiproliferative actions of these products highlight HO-1 as a key endogenous antioxidant and cytoprotective gene. This study was designed to further characterize HO-1 induction of Rhizoma Chuanxiong through bioactivity-guided fractionation. All isolated fractions were assayed for HO-1 induction in human HepG2 cell line at mRNA and protein levels. Based on chromatographic profiling, nuclear magnetic resonance (NMR) and mass spectrometric analysis, the active compounds were identified as senkyunolide-H and its stereoisomer senkyunolide-1. Both senkyunolide isomers inhibited the formation of reactive oxygen species and lipid peroxidation and enhanced the cellular resistance to hydrogen peroxide-induced oxidative damage. Notably, heme oxygenase inhibitor tin protoporphyrin IX (SnPP) significantly suppressed the antioxidant activity of senkyunolide stereoisomers. Thus, this study demonstrated that senkyunolide-H and -I attenuated oxidative damage via activation of HO-1 pathway. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:380 / 389
页数:10
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