Preconditioning with Ginkgo biloba (EGb 761®) provides neuroprotection through HO1 and CRMP2.
Ginkgo biloba/EGb 761® (EGb 761) is a popular and standardized natural extract used worldwide for the treatment of many ailments. Although EGb 761 is purported to have a plethora of benefits, here, we were interested to study the neuroprotective properties of EGb 761 and its components and determine whether nuclear factor E2 (Nrf2)/heme oxygenase 1 (HO1) induction of the collapsin response mediator protein 2 (CRMP2) pathway contributes to neuroprotection. Mice were pretreated with EGb 761 or one of its constituents (bilobalide, ginkgolide A, ginkgolide B, and terpene free material [TFM]) for 7days and then subjected to transient middle cerebral artery occlusion (tMCAO) and 48 h of reperfusion. All components except TFM significantly reduced infarct volumes and neurologic deficits. Next, we examined the antioxidant and neuritogenic properties of EGb 761 in primary neurons. Compared with vehicle-treated cells, pretreatment with EGb 761 significantly enhanced the survival of neurons exposed to tertiary butylhydroperoxide (t-BuOOH), hydrogen peroxide (H2O2), and N-methyl-D-aspartate (NMDA). Bilobalide and ginkgolide A also protected cells against NMDA-induced excitotoxicity. Immunofluorescence and Western blot analysis showed that EGb 761 pretreatment significantly increased the protein expression levels of Nrf2, HO1, GAPDH, β-actin, CRMP2, and histone H3 during t-BuOOH-induced oxidative stress. These findings suggest that EGb 761 not only has antioxidant activity but also neuritogenic potential. Demonstrating such effects for possible drug discovery may prove beneficial in stroke and ischemic brain injury.
Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614, USA.
Shadia E
SE
Nada
Zahoor A
ZA
Shah
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D020441:Ginkgo biloba; D046934:Ginkgolides / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D000096983:Ginkgo Extract
D046934:Ginkgolides; D051547:Heme Oxygenase-1; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D010936:Plant Extracts; C095114:collapsin response mediator protein-2; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract