Roots of Lithospermum erythrorhizon promotes retinal cell survival in optic nerve crush-induced retinal degeneration

Exp Eye Res. 2021 Feb:203:108419. doi: 10.1016/j.exer.2020.108419. Epub 2020 Dec 28.

Abstract

Lithospermum erythrorhizon (L. erythrorhizon), used in traditional medicine, is a potent wound healing, anti-inflammatory and antioxidant plant. However, the effects of L. erythrorhizon on retinal degenerative diseases remain unknown. Here, we explored the protective effects of L. erythrorhizon in in vitro and in vivo retinal degeneration. We found that ethanol extract of L. erythrorhizon (EELE) and the dichloromethane fraction of L. erythrorhizon (MCLE) significantly increased cell viability under glutamate/BSO-induced excitotoxicity/oxidative stress in R28 cells. Treatment with EELE and MCLE reduced the intracellular reactive oxygen species (ROS) and the levels of apoptotic proteins, such as cleaved PARP and cleaved caspase-3. Furthermore, oral administration of EELE and MCLE in an in vivo optic nerve crush mouse model decreased RGC cell death and increased retinal thickness. The major compound between EELE and MCLE was found to be lithospermic acid A (LAA), which has been shown to prevent the elevation of ROS in R28. Therefore, EELE and MCLE have protective effects against the death of retinal cells in vitro and in vivo, and the major compound, LAA, has an antioxidant effect on retinal cells, suggesting that EELE and MCLE could be beneficial agents for retinal degenerative diseases, including glaucoma.

Keywords: Apoptosis; Glaucoma; Lithospermum erythrorhizon; Optic nerve crush; Oxidative stress; Retinal degeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism
  • Benzofurans / pharmacology
  • Cell Culture Techniques
  • Cell Survival / drug effects
  • Chromatography, High Pressure Liquid
  • Depsides / pharmacology
  • Electrophoresis, Polyacrylamide Gel
  • Lithospermum / chemistry*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Crush
  • Optic Nerve Injuries / drug therapy*
  • Optic Nerve Injuries / metabolism
  • Oxidative Stress / drug effects
  • Phytotherapy / methods*
  • Plant Extracts / therapeutic use*
  • Plant Roots / chemistry*
  • Reactive Oxygen Species / metabolism
  • Retinal Degeneration / drug therapy*
  • Retinal Degeneration / metabolism
  • Retinal Ganglion Cells / drug effects*
  • Retinal Ganglion Cells / metabolism
  • Tomography, Optical Coherence

Substances

  • Apoptosis Regulatory Proteins
  • Benzofurans
  • Depsides
  • Plant Extracts
  • Reactive Oxygen Species
  • lithospermic acid