Moutan Cortex Radicis (MCR) is one of the most widely used Oriental medicines. In this study, we assessed the reducing effect of ethanol extract of MCR on hydrogen peroxide-induced reactive oxygen production, the main cause of cell damage or death in PC12 cells. The viability of cells treated with 1 mg/ml of MCR was significantly restored from that of oxidative-stressed PC12 cells. Measurement of intracellular reactive oxygen species (ROS) generation was determined using the H2DCFDA assay. MCR at 1-0.01 mg/ml concentration inhibited ROS production in oxidative-stressed cells. To identify candidate genes responsible for the anti-oxidative effects of MCR on PC12 cells, an oligonucleotide microarray analysis was performed. The result of gene expression profiles showed that 10 genes were up-regulated and 7 were down-regulated in MCR plus hydrogen peroxide treated cells compared with hydrogen peroxide treated cells. Among them, heme oxygenase (HO) and cathechol-O-methyltransferase (COMT) are related to regulation of ROS generation and the others are known to regulate cell survival and progression. Subsequently, we performed real-time RT-PCR to quantify the ROS related gene. MCR treatment increased the expression of HO by 370% and COMT by 280% at the concentration of 1 mg/ml. These findings suggest that MCR inhibits the production of ROS and cytotoxicity by oxidative-stressed PC12 cells through over-expression of HO and COMT. © 2005 Pharmaceutical Society of Japan.
Cathechol-O-methyltransferase, heme oxygenase; Moutan cortex radicis; Oligonucleotide microarray; Reactive oxygen species
EMTREE drug terms: alcohol derivative; catechol methyltransferase; heme oxygenase; hydrogen peroxide; Paeonia suffruticosa extract; reactive oxygen metabolite
EMTREE medical terms: animal cell; antioxidant activity; article; cell damage; cell death; cell strain; cell survival; cell viability; concentration response; controlled study; cytotoxicity; DNA microarray; down regulation; drug isolation; gene control; gene expression; gene overexpression; nonhuman; nucleotide sequence; oxidative stress; Paeonia suffruticosa; rat; reverse transcription polymerase chain reaction; upregulation
MeSH: Animals; Down-Regulation; Gene Expression Profiling; Neurosecretory Systems; Oxidative Stress; Paeonia; PC12 Cells; Plant Extracts; Rats; Reactive Oxygen Species; Up-Regulation
Medline is the source for the MeSH terms of this document.
Molecular Sequence Numbers: GENBANK,AF020757(referenced), AF020758(referenced), AF028603(referenced), AI029917(referenced), AI179610(referenced), AJ222813(referenced), E12625(referenced), J02722(referenced), M74223(referenced), M93257(referenced), M99485(referenced), S47609(referenced), S68135(referenced), S73424(referenced), U08290(referenced), U14414(referenced), U77777(referenced), X06769(referenced), X07729(referenced), X16002(referenced)
Chemicals and CAS Registry Numbers: catechol methyltransferase, 9012-25-3; heme oxygenase, 9059-22-7; hydrogen peroxide, 7722-84-1;Plant Extracts; Reactive Oxygen Species