title: Protective effects of the compounds isolated from the seed of Psoralea corylifolia on oxidative stress-induced retinal damage.
abstract: The mechanism underlying glaucoma remains controversial, but apoptosis caused by increased levels of reactive oxygen species (ROS) is thought to play a role in its pathogenesis. We investigated the effects of compounds isolated from Psoralea corylifolia on oxidative stress-induced cell death in vitro and in vivo. Transformed retinal ganglion cells (RGC-5) were treated with l-buthione-(S,R)-sulfoximine (BSO) and glutamate in the presence or with pre-treatment with compound 6, bakuchiol isolated from P. corylifolia. We observed reduced cell death in cells pre-treated with bakuchiol. Moreover, bakuchiol inhibited the oxidative stress-induced decrease of mitochondrial membrane potential (MMP, ΔΨm). Furthermore, while intracellular Ca(2+) was high in RGC-5 cells after exposure to oxidative stress, bakuchiol reduced these levels. In an in vivo study, in which rat retinal damage was induced by intravitreal injection of N-methyl-d-aspartate (NMDA), bakuchiol markedly reduced translocation of AIF and release of cytochrome c, and inhibited up-regulation of cleaved caspase-3, cleaved caspase-9, and cleaved PARP. The survival rate of retinal ganglion cells (RGCs) 7days after optic nerve crush (ONC) in mice was significantly decreased; however, bakuchiol attenuated the loss of RGCs. Moreover, bakuchiol attenuated ONC-induced up-regulation of apoptotic proteins, including cleaved PARP, cleaved caspase-3, and cleaved caspase-9. Bakuchiol also significantly inhibited translocation of mitochondrial AIF into the nuclear fraction and release of mitochondrial cytochrome c into the cytosol. These results demonstrate that bakuchiol isolated from P. corylifolia has protective effects against oxidative stress-induced retinal damage, and may be considered as an agent for treating or preventing retinal degeneration.
authors.affiliation: Functional Food Center, Korea Institute of Science and Technology (KIST) Gangneung Institute, Gangneung, Republic of Korea.
authors.forename: Kyung-A
authors.initials: KA
authors.lastname: Kim
authors.forename: Sang Hee
authors.initials: SH
authors.lastname: Shim
authors.forename: Hong Ryul
authors.initials: HR
authors.lastname: Ahn
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Jung
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D016202:N-Methylaspartate / Q000633:toxicity; D009900:Optic Nerve / Q000473:pathology; D018384:Oxidative Stress; D010636:Phenols / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D029907:Psoralea / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000473:pathology*; D012164:Retinal Diseases / Q000139:chemically induced* / Q000188:drug therapy; D012639:Seeds / Q000737:chemistry*
chemical_list: D010636:Phenols; D010936:Plant Extracts; D016202:N-Methylaspartate; C012765:bakuchiol