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

ABSTRACT

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:

• Huperzine A
• acetylcholinesterase
• nicotinic receptors
• GABAergic transmission
• excitotoxicity
• neuroprotection

Acknowledgements

The authors express gratitude to Dr. Rejean Guerriero for his contribution to the artwork in Figure 2.

Declaration of interest

This work was supported by DoD 09082006 (A Rotenberg, S Schachter), CIMIT (A Rotenberg, S Schachter), and research support from the Harvard Medical School(S Schachter). A. Rotenberg’s research is also supported by grants from NIH NINDS (R01NS066019), NIH NIMH (R21MH104318), Boston Children’s Hospital Translational Research Program, the Smith Family Foundation, and King Saud University. A. Rotenberg is co-founder of and consultant to Neuro’motion Inc., consultant to NeuroRex Inc., and receives or has received in recent past research support from Sage therapeutics Inc., Wuhan Yirude Medical Equipment New Technology Co., Ltd., Neuropace Inc., Nexstim Inc., Neuronetics Inc, Brainsway Inc. and Eisai Pharmaceuticals. None of the aforementioned relationships conflict with work described in this manuscript. S. Schachter is inventor on a patent for the use of Huperzine for treatment of epilepsy, which is licensed by Harvard Medical School, to Biscayne Pharmaceuticals, Inc., in which he holds less than 5% equity and for which he serves on the scientific advisory board. J. Johnstone is an employee of Biscayne Pharmaceuticals, Inc., which has licensed technology from Harvard Medical School involving the use of Huperzine for epilepsy disorders. He holds less than 5% equity in Biscayne Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.