Silibinin alleviates DNA damage, mitochondrial dysfunction, and apoptosis caused by oxidative stress in human retinal pigment epithelial cells

Abstract

Background

Silibinin, a flavonolignan, is known to have a variety of pharmacological activities, including antioxidant activity, but its antioxidant mechanism in the eye is unclear.

Objective

This study aimed to evaluate whether silibinin could protect human retinal pigment epithelial ARPE-19 cells from oxidative injury.

Results

Silibinin attenuated cell viability reduction and DNA damage in ARPE-19 cells treated with hydrogen peroxide (H₂O₂), while inhibiting intracellular reactive oxygen species (ROS) production and preserving diminished glutathione (GSH). Silibinin also antagonized H₂O₂-induced inhibition of the expression and activity of antioxidant enzymes, such as GSH peroxidase and manganese superoxide dismutase, which was associated with inhibition of mitochondrial ROS production. Moreover, silibinin rescued ARPE-19 cells from H₂O₂-induced apoptosis by restoring the reduced Bcl-2/Bax ratio and reducing caspase-3 activation. In addition, silibinin suppressed the release of mitochondrial cytochrome c into the cytoplasm, which was achieved by interfering with mitochondrial membrane disruption.

Conclusion

These findings imply that silibinin has potent ROS scavenging activity with the potential to protect against oxidative stress-mediated ocular diseases.