Huperzine A as a neuroprotective and antiepileptic drug: a review of preclinical research

Expert Rev Neurother. 2016 Jun;16(6):671-80. doi: 10.1080/14737175.2016.1175303. Epub 2016 Apr 20.


Huperzine A (HupA) is an acetylcholinesterase (AChE) inhibitor extracted from Huperzia Serrata, a firmoss, which has been used for various diseases in traditional Chinese medicine for fever and inflammation. More recently, it has been used in Alzheimer's disease and other forms of dementia with a presumed mechanism of action via central nicotinic and muscarinic receptors. HupA is marketed as a dietary supplement in the U.S. This article reviews newly proposed neuroprotective and anticonvulsant HupA properties based on animal studies. HupA exerts its effects mainly via α7nAChRs and α4β2nAChRs, thereby producing a potent anti-inflammatory response by decreasing IL-1β, TNF-α protein expression, and suppressing transcriptional activation of NF-κB signaling. Thus, it provides protection from excitotoxicity and neuronal death as well as increase in GABAergic transmission associated with anticonvulsant activity.

Keywords: GABAergic transmission; Huperzine A; acetylcholinesterase; excitotoxicity; neuroprotection; nicotinic receptors.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkaloids* / therapeutic use
  • Animals
  • Anticonvulsants* / therapeutic use
  • Cholinesterase Inhibitors / pharmacology
  • Epilepsy / drug therapy*
  • Humans
  • Neuroprotective Agents / therapeutic use
  • Sesquiterpenes* / therapeutic use


  • Alkaloids
  • Anticonvulsants
  • Cholinesterase Inhibitors
  • Neuroprotective Agents
  • Sesquiterpenes
  • huperzine A