Aucuba japonica Extract and Aucubin Prevent Desiccating Stress-Induced Corneal Epithelial Cell Injury and Improve Tear Secretion in a Mouse Model of Dry Eye Disease

Molecules. 2018 Oct 11;23(10):2599. doi: 10.3390/molecules23102599.

Abstract

Dry eye disease is affected by a broad range of causes such as age, lifestyle, environment, medication and autoimmune diseases. These causes induce tear instability that activates immune cells and promotes expression of inflammatory molecules. In this study, we investigated the therapeutic effects of an ethanolic extract of Aucuba japonica (AJE) and its bioactive compound, aucubin, on dry eye disease. The human corneal cells were exposed to desiccation stress induced by exposing cells to air, so that viability was decreased. On the other hand, pre-treatment of AJE and aucubin restored cell survival rate depending on the dose under the dry condition. This result was confirmed again by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The mRNA expression of inflammatory molecules was reduced by the pretreatment of AJE and aucubin under the dry state. The therapeutic effects of AJE and aucubin were examined in the animal model for dry eye induced by unilateral excision of the exorbital lacrimal gland. Declined tear volumes and corneal irregularity in the dry eye group were fully recovered by the administration of AJE and aucubin. The apoptotic cells on the cornea were also decreased by AJE and aucubin. Therefore, this study suggests that administration of AJE can be a novel therapeutic for dry eye disease and that the pharmacological activities of AJE may be in part due to its bioactive compound, aucubin.

Keywords: Aucuba japonica; aucubin; cornea; dry eye; tear.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Survival / drug effects
  • Chromatography, High Pressure Liquid
  • Cytokines / genetics
  • Cytokines / metabolism
  • Desiccation
  • Disease Models, Animal
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelium, Corneal / drug effects
  • Epithelium, Corneal / injuries*
  • Epithelium, Corneal / metabolism*
  • Epithelium, Corneal / pathology
  • Gene Expression
  • Inflammation Mediators / metabolism
  • Iridoid Glucosides / analysis
  • Iridoid Glucosides / chemistry
  • Iridoid Glucosides / pharmacology*
  • Magnoliopsida / chemistry*
  • Mice
  • Molecular Structure
  • Plant Extracts / analysis
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Protective Agents / pharmacology
  • Rats
  • Tears*
  • Xerophthalmia / drug therapy
  • Xerophthalmia / etiology
  • Xerophthalmia / metabolism*

Substances

  • Cytokines
  • Inflammation Mediators
  • Iridoid Glucosides
  • Plant Extracts
  • Protective Agents
  • aucubin