The neuroprotective effect of hesperidin in NMDA-induced retinal injury acts by suppressing oxidative stress and excessive calpain activation

Sci Rep. 2017 Jul 31;7(1):6885. doi: 10.1038/s41598-017-06969-4.


We found that hesperidin, a plant-derived bioflavonoid, may be a candidate agent for neuroprotective treatment in the retina, after screening 41 materials for anti-oxidative properties in a primary retinal cell culture under oxidative stress. We found that the intravitreal injection of hesperidin in mice prevented reductions in markers of the retinal ganglion cells (RGCs) and RGC death after N-methyl-D-aspartate (NMDA)-induced excitotoxicity. Hesperidin treatment also reduced calpain activation, reactive oxygen species generation and TNF-α gene expression. Finally, hesperidin treatment improved electrophysiological function, measured with visual evoked potential, and visual function, measured with optomotry. Thus, we found that hesperidin suppressed a number of cytotoxic factors associated with NMDA-induced cell death signaling, such as oxidative stress, over-activation of calpain, and inflammation, thereby protecting the RGCs in mice. Therefore, hesperidin may have potential as a therapeutic supplement for protecting the retina against the damage associated with excitotoxic injury, such as occurs in glaucoma and diabetic retinopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Calpain / metabolism*
  • Cells, Cultured
  • Disease Models, Animal
  • Evoked Potentials, Visual / drug effects
  • Hesperidin / administration & dosage*
  • Hesperidin / pharmacology
  • Male
  • Mice
  • N-Methylaspartate / adverse effects*
  • Neuroprotective Agents / administration & dosage*
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress / drug effects
  • Retina / cytology
  • Retina / drug effects
  • Retina / metabolism
  • Retinal Diseases / chemically induced
  • Retinal Diseases / drug therapy*
  • Retinal Diseases / genetics
  • Retinal Diseases / metabolism
  • Retinal Ganglion Cells / cytology*
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / metabolism
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / genetics


  • Neuroprotective Agents
  • Tumor Necrosis Factor-alpha
  • N-Methylaspartate
  • Hesperidin
  • Calpain