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: Kyung-A Kim, Sang Hee Shim, Hong Ryul Ahn, Sang Hoon Jung
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 269 Issue 2 Pg. 109-20 (Jun 01 2013) ISSN: 1096-0333 [Electronic] United States
• PMID: 23545180 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Phenols
• Plant Extracts
• N-Methylaspartate
• bakuchiol

Topics

• Animals
• Cell Line
• Cell Survival
• Male
• Mice
• Mice, Inbred ICR
• Molecular Structure
• N-Methylaspartate (toxicity)
• Optic Nerve (pathology)
• Oxidative Stress
• Phenols (pharmacology)
• Plant Extracts (chemistry, pharmacology)
• Psoralea (chemistry)
• Rats
• Rats, Sprague-Dawley
• Retina (pathology)
• Retinal Diseases (chemically induced, drug therapy)
• Seeds (chemistry)