Induction of heme oxygenase-1 by Ginkgo biloba extract but not its terpenoids partially mediated its protective effect against lysophosphatidylcholine-induced damage.
In this study, we examined whether Ginkgo Biloba Extract and its terpenoid constituents protect against oxidative stress through actions on heme oxygenase (HO) gene expression and activity. HO-1 and glutathione peroxidase (GPx) gene expressions were examined by reverse transcription polymerase chain reaction (RT-PCR) analysis, HO activity and GPx enzyme activity were analysed by spectrophotometric assay. Pretreatment of H9c2 myocytes with 100-500 microgml(-1)Ginkgo Biloba Extract caused induction of HO-1 gene expression and a significant increase in HO activity; 30 microgml(-1)ginkgolide B and 30 microgml(-1)bilobalide had little effect. Treatment with Ginkgo Biloba Extract for 24 h also significantly increased GPx gene expression and GPx enzyme activity. Pretreatment with Ginkgo Biloba Extract, ginkgolide B and bilobalide protected myocytes against lysophosphatidylcholine (LPC)-induced damage. The protective effect of Ginkgo Biloba Extract against LPC-induced damage was partially suppressed by a HO inhibitor, Zinc protoporphyrin-IX (ZnPP-IX), while ZnPP-IX did not suppress the protective effect of ginkgolide B or bilobalide. Furthermore, pretreatment with hemin, biliverdin or bilirubin reduced cytotoxicity induced by LPC. These results suggest that induction of HO-1 by Ginkgo Biloba Extract but not its terpenoid constituents may play a beneficial role in oxidative stress. The mechanism of Ginkgo Biloba Extract-induced HO-1 gene expression and the increase in HO activity may be related to alteration of intracellular glutathione levels.
Chen
J X
JX
Department of Pharmacology, Hunan Medical University, Changsha, 410078, P.R. China. Jian-xiong.chen@mcmail.vanderbilt.edu
Zeng
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Lai
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D000818:Animals; D001663:Bilirubin / Q000494:pharmacology; D001664:Biliverdine / Q000494:pharmacology; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005333:Fetus; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020441:Ginkgo biloba / Q000737:chemistry*; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D051547:Heme Oxygenase-1; D008244:Lysophosphatidylcholines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D051381:Rats; D013729:Terpenes / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D008244:Lysophosphatidylcholines; D010936:Plant Extracts; D013729:Terpenes; D005979:Glutathione Peroxidase; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D001664:Biliverdine; D001663:Bilirubin