Protective effects of the compounds isolated from the seed of Psoralea corylifolia on oxidative stress-induced retinal damage.

Kyung-A Kim, Sang Hee Shim, Hong Ryul Ahn, Sang Hoon Jung

Functional Food Center, Korea Institute of Science and Technology (KIST) Gangneung Institute, Gangneung, Republic of Korea.

Toxicology and applied pharmacology 2013 Jun 1

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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. Copyright © 2013 Elsevier Inc. All rights reserved.

Citation

Kyung-A Kim, Sang Hee Shim, Hong Ryul Ahn, Sang Hoon Jung. Protective effects of the compounds isolated from the seed of Psoralea corylifolia on oxidative stress-induced retinal damage. Toxicology and applied pharmacology. 2013 Jun 1;269(2):109-20