Neuroprotective Effect of Huperzine A on d-Galactose-Induced Hearing Dysfunction

Ear Nose Throat J. 2021 Jun;100(3_suppl):269S-276S. doi: 10.1177/0145561319864570. Epub 2019 Sep 25.


Background: Administration of d-galactose (d-gal) has been used to create animal models of neurodegenerative diseases, and huperzine A has been used to treat the neurodegenerative diseases such as Alzheimer disease.

Methods: An animal model of hearing dysfunction was established by administration of d-gal in the rats, and the effect of huperzine A on d-gal-induced abnormal hearing function and cochlear damage was investigated. Senescence of the cochlear tissues was examined by β-galactase staining, and messenger RNA expression of inflammatory cytokines was quantified by real-time reverse transcription-polymerase chain reaction (RT-PCR).

Results: It was found that d-gal significantly increased auditory brainstem response (ABR) threshold and cellular senescence and decreased neurofilament in the cochlear tissues. Huperzine A could significantly attenuate d-gal-induced increase of ABR threshold and cellular senescence as well as reduction of neurofilament. Moreover, huperzine A could inhibit d-gal-induced activation of nuclear factor kappa-B (NF-κB) in Schwann cells and significantly blocked d-gal-stimulated gene expression of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α.

Conclusion: These findings suggested that d-gal causes hearing dysfunction by inflammatory injury of cochlear neurons and that huperzine A could prevent hearing loss by protecting d-gal-induced physical damage of cochlear tissues.

Keywords: animal model; auditory brainstem response; d-galactose; hearing loss; huperzine A; neurodegenerative disease.

MeSH terms

  • Alkaloids / pharmacology*
  • Animals
  • Cellular Senescence / drug effects
  • Cochlea / innervation
  • Cochlea / pathology
  • Disease Models, Animal
  • Evoked Potentials, Auditory, Brain Stem / drug effects
  • Galactose
  • Hearing Loss / chemically induced
  • Hearing Loss / drug therapy*
  • Intermediate Filaments / drug effects
  • Neurons / drug effects
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Sesquiterpenes / pharmacology*


  • Alkaloids
  • Neuroprotective Agents
  • Sesquiterpenes
  • huperzine A
  • Galactose