(−)-Huperzine A (HupA) is an acetylcholinesterase (AChE) inhibitor with an IC50 value of 82 nmol/L  and acts as an antagonist of the N-methyl-d-aspartate (NMDA) receptor .
AChE is the key brain enzyme responsible for the rapid degradation of the neurotransmitter acetylcholine. AChE inhibitors are probably useful in the amelioration of the Alzheimer’s symptomatology .
It was found that NMDA markedly reduced AChE activities . In rat dissociated hippocampal neurons, HupA inhibited the NMDA-induced current. In neurons, 100 µM HupA, NMDA-induced currents were 55.7 ± 4.9% of the control values. The binding molecular ratio of NMDA receptor: HupA is 1:1. The inhibition of NMDA receptor by HupA is not competitive . HupA significantly increased the phosphorylation levels of both glycogen synthase kinase (GSK)-3α protein and GSK-3β protein in APPsw-overexpressing cells . Activated GSK-3 consequently decreased acetylcholine (ACh) level in the striatum .
Treated with doses of (−)-huperzine A, AChE−/− mice showed no toxic symptoms and had normal levels of AChE. This demonstrated the specificity of (−)-huperzine A as an inhibitor of AChE at the dose used in vivo . In rat whole brain, oral administration of HupA at a dose of 1.5 μmol/kg (3.6 mg/kg) obtained a maximum inhibition of AChE at 60 min and this maximum inhibition was maintained for 360 min .
. MA Xiao-Chao, XIN Jian, WANG Hai-Xue, et al. Acute effects of huperzine A and tacrine on rat liver. Acta Pharmacol ogica Sinica, 2003, 24(3):247-250.
. Zhong Ming Qian and Ya Ke. Huperzine A: is it an effective disease-modifying drug for Alzheimer's disease? Frontiers in Aging Neuroscience, 2014, 6:216.
. V. Rajendran, Suo-Bao Rong, Ashima Saxena, et al. Synthesis of a hybrid analog of the acetylcholinesterase inhibitors huperzine A and huperzine B. Tetrahedron Letters, 2001, 42: 5359-5361.
. J. R. Delfs, D. M. Saroff, Y. Nishida, et al. Effects of NMDA and its antagonists on ventral horn cholinergic neurons in organotypic roller tube spinal cord cultures. J. Neural Transm., 1997, 104(1):31-51.
. J. M. Zhang and G. Y. Hu. Huperzine A, a nootropic alkaloid, inhibits N-methyl-D-aspartate-induced current in rat dissociated hippocampal neurons. Neuroscience, 2001, 105(3):663-9.
. L. Zhao, C. B. Chu, J. F. Li, et al. Glycogen synthase kinase-3 reduces acetylcholine level in striatum via disturbing cellular distribution of choline acetyltransferase in cholinergic interneurons in rats. Neuroscience, 2013, 255:203-11.
. Ellen G. Duysen, Bin Li, Sultan Darvesh, et al. Sensitivity of butyrylcholinesterase knockout mice to (−)-huperzine A and donepezil suggests humans with butyrylcholinesterase deficiency may not tolerate these Alzheimer’s disease drugs and indicates butyrylcholinesterase function in neurotransmission. Toxicology, 2007, 233:60-69.
. Rui Wang, Han Yan and Xi-can Tang. Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacologica Sinica, 2006, 27:1-26.
|Physical Appearance||A solid|
|Storage||Store at -20°C|
|Solubility||≥12.1mg/mL in DMSO|
|Canonical SMILES||C/C=C1[[email protected]@]2(N)C3=C(NC(C=C3)=O)C[[email protected]]/1([H])C=C(C)C2|
|Shipping Condition||Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request|
|General tips||For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.|
|Description||(-)-Huperzine A is a potent, highly specific and reversible inhibitor of acetylcholinesterase (AChE) with Ki of 7 nM, exhibiting 200-fold more selectivity for G4 AChE over G1 AChE.|
|Targets||Acetylcholinesterase (G4 form)|
|IC50||7 nM (Ki)|
Quality Control & MSDS
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Three different models were used to evaluate the intestinal permeability of huperzine A, including in vitro Caco-2 and parallel artificial membrane permeation assay models and the ex vivo Ussing chamber model, in which results suggest the permeability rate was strongly ionization dependent and increased with elevation of the donor medium PH. Though the majority of huperzine A passes through intestinal border through passive transcellular diffusion, a small fraction depending on the degree of ionization is absorbed by the paracellular route.
Huperzine A, an AchEl used to treat cognitive deterioration associated with AD, has side effects associated with increased cholinergic activity in the gastrointestinal system. Following oral administration of huperine A to mice, a single dose significantly inhibited the AChE activity in the stomach and duodenum and significantly increased the gastrointestinal motility; while multiple doses caused no significant changes in both.
Cineole and terpineol synergistically increased the transdermal delivery of huperzine from microemulsions in Franz-type diffusion cells through increasing the partition and diffusion coefficients of huperzine A, in which ATR-FTIR analysis revealed the mechanism of the synergistic effects was due to increasing the disorderliness and fluidity of SC lipid alkyl chains, disrupting the structure of keratin in SC, and extracting SC lipids.
Huperzine A is a novel reversible and selective AchE inhibition that is isolated from Chinese herb Hyperzia serrate (Thunb) Trev.
As a drug extracted from a Chinese herb to treat Alzheimer’s disease, huperzine A was evaluated for its beneficial and harmful effects.