Perhaps the most exciting life-enhancing agent is huperzine A
(HupA), which, based on the published research, I believe is
the most potent memory-enhancing agent available, far superior
to gingko. Studies also routinely find HupA to be significantly
more potent than the prescription drug for Alzheimer's disease
tacrine. HupA improves memory by increasing levels of the
memory-essential neurotransmitter acetylcholine by inhibiting
acetylcholinesterase, which breaks down acetylcholine. HupA
is available over the counter at many health-food stores
and is a naturally occurring chemical from Chinese moss.
(Search "huperzine": http://www.ncbi.nlm.nih.gov/PubMed)
The following studies found that HupA is also neuroprotective.
Neurosci Lett 1999 Nov 12;275(2):73-6
Huperzine A protects rat pheochromocytoma cells against
hydrogen peroxide-induced injury.
Xiao XQ, Yang JW, Tang XC
State Key Laboratory of Drug Research, Shanghai Institute
of Materia Medica, Chinese Academy of Sciences, People's
Republic of China.
The effects of Huperzine A (HupA), a novel acetylcholinesterase
inhibitor, on hydrogen peroxide (H2O2) induced cell lesion, level
of lipid peroxidation and antioxidant enzyme activities were
investigated in rat pheochromocytoma line PC12. Following a 6-h
exposure of the cells to H2O2 (200 microM), a marked reduction
in cell survival and activities of glutathione peroxidase and
catalase, as well as increased production of malondialdehyde
(MDA) were observed. Pretreatment of the cells with HupA
(0.1-10.0 microM) prior to H2O2 exposure significantly elevated
the cell survival and antioxidant enzyme activities and decreased
the level of MDA. Our results indicated that in addition to its
anticholinesterase effects, HupA had protective effects against
free radical-induced cell toxicity, which might be beneficial
for the treatment of Alzheimer's disease.
Neuroreport 1997 Mar 3;8(4):963-8
Huperzine A, a potential therapeutic agent for dementia, reduces
neuronal cell death caused by glutamate.
Ved HS, Koenig ML, Dave JR, Doctor BP
Division of Biochemistry, Walter Reed Army Institute of Research,
Washington, DC 20307-5100, USA.
Huperzine a, a potential therapeutic agent for Alzheimer's disease,
inhibits acetylcholinesterase in primary cultures derived from
forebrain, hippocampus, cortex and cerebellum of embryonic rat
brain. Glutamate induces cell death in cultures from all these
brain regions. Maximum cell toxicity was observed in cerebellar
cultures. Pretreatment of cell cultures with Huperzine A reduced
cell toxicity, as evidenced by cytotoxicity assay and general
morphology. Huperzine A pretreatment also reduced glutamate-
induced calcium mobilization, but did not affect elevations in
intraneuronal free Ca2+ ([Ca]i) caused by KCl or (-)Bay K 8644.
The data suggest that Huperzine A could be a potent
neuroprotective agent not only where cholinergic neurons are
impaired, but also under conditions in which glutamatergic
functions are compromised.
Fundam Clin Pharmacol 1997;11(5):387-94
Efficacy of huperzine in preventing soman-induced seizures,
neuropathological changes and lethality.
Lallement G, Veyret J, Masqueliez C, Aubriot S, Burckhart MF,
Unite de Neurotoxicologie, CRSSA, La Tronche, France.
Huperzine A (HUP) is a potent reversible inhibitor of
acetylcholinesterase (AChE) that crosses the blood-brain
barrier. Its ability to prevent seizures and subsequent
hippocampal neuropathological changes induced by the
organophosphate soman was studied in guinea pigs. Results
were compared to guinea pigs treated with pyridostigmine
(PYR, 0.2 mg/kg, subcutaneously). HUP pretreatment at 0.5
mg/kg, intraperitoneally, totally prevented seizures and
ensured the survival of all animals for 24 h after intoxication.
Hippocampal tissue was then free of any neuronal damage.
Comparatively, all animals pretreated with PYR exhibited
epileptic activity after soman poisoning and five of six
animals died. Examination of the hippocampus of the only
surviving guinea pig pretreated with PYR showed extensive
neuropathological changes. Although HUP or PYR induced
similar inhibitions of blood AChE activity, only HUP
pretreatment led to a decrease in central AChE activity.
In binding studies on guinea-pig brain homogenates, HUP
had no affinity for muscarinic, alpha-amino-3-hydroxy-5-
methyl-4-isoxazole propionic acid (AMPA) and gamma-
aminobutyric acid (GABA)A receptors and only a very low
one for N-methyl-D-aspartate (NMDA) receptors. In
conclusion, HUP, unlike PYR, protects against soman-
induced convulsions and neuropathological changes in the
hippocampus. This efficacy seems to be related to a
protection by HUP of both peripheral and central stores of AChE.
GODDARD'S JOURNAL: http://www.erols.com/igoddard/journal.htm
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