(-)-Huperzine A (HupA) , an active Lycopodium alkaloid extracted from the traditional Chinese herb, is a potent, selective and reversible acetylcholinesterase (AChE) inhibitor and has been widely used in China for the treatment of Alzheimer's disease (AD).

AChE (G4 form):7 nM(Ki)

In both animal models and patients with Alzheimer's Disease (AD), (-)-Huperzine A has been shown to improve learning and memory impairments. Compared to the control group treated with saline, significant inhibition of acetylcholinesterase (AchE) activity was observed in the cortex, striatum, hippocampus, medulla, septal nuclei, cerebellum, and thalamus of rats 30 minutes post-mortem.

Compared to tacrine, strychnine, galantamine, and carbachol, (-)-Huperzine A exhibits stronger inhibition of acetylcholinesterase (AChE) activity but has the least effect on butyrylcholinesterase (BuChE). (-)-Huperzine A protects cells against glutamate, hydrogen peroxide, β-amyloid, ischemia, and astrosporine-induced cytotoxicity and apoptosis. This protective function is achieved through a series of processes including the regulation of apoptotic protein expression (such as Bcl-2, Bax, p53, and caspase-3), alleviation of oxidative stress, mitochondrial protection, upregulation of nerve growth factor and its receptors, and interference with amyloid precursor protein metabolism. Notably, (-)-Huperzine A preferentially inhibits the tetrameric form of AChE (G4 form).