Induction of heme oxygenase 1 by Ginkgo biloba in neuronal cultures and potential implications in ischemia.
Ginkgo biloba extract (EGb 761) is a standardized extract originating in traditional Chinese medicine. Ginkgo biloba dried leaves have been used for centuries to treat various neurological conditions. The constituents from the extract are likely to have synergistic effects that have been shown to be protective against oxidative stress injury. However, the cellular mechanisms of protection afforded by Ginkgo biloba are still unclear. The cascade leading to neuronal cell death in acute and chronic neurodegenerative conditions, such as cerebral ischemia and Alzheimer's disease, has been postulated to be mediated by free radical damage. We tested the hypothesis that the neuroprotective action of EGb 761 could be due partially to an induction of heme oxygenase I (HO1). We and others have previously reported that modulation of HO total activity may well have direct physiological implications in stroke and in Alzheimer's disease. Heme oxygenase acts as an antioxidant enzyme by degrading heme into iron, carbon monoxide, and biliverdin which is rapidly converted into bilirubin. Through the use of primary neuronal cultures, we demonstrated that EGb 761 induces HO1 in a dose-dependent manner (0, 10, 50, 100 and 500 microg/ml) and time-dependent manner with a maximal induction at 8 hr. We are proposing that several of the protective effects of EGb 761 in ischemia could be mediated through beneficial actions of heme degradation and its metabolites.
Zhuang
Hean
H
Pin
Sokhon
S
Christen
Yves
Y
Doré
Sylvain
S
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002248:Carbon Monoxide / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D020441:Ginkgo biloba; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D051547:Heme Oxygenase-1; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D000096983:Ginkgo Extract
D000975:Antioxidants; D002248:Carbon Monoxide; D006418:Heme; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D010936:Plant Extracts; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C496542:Hmox1 protein, mouse