ABSTRACT
Introduction ............................................................................................................ 310 Phytobiology .......................................................................................................... 310 Biochemistry .......................................................................................................... 311 Pharmacology ........................................................................................................ 311
Anticholinesterase Action ................................................................................. 311 In Vitro .......................................................................................................... 312 In Vivo .......................................................................................................... 312
Effects on Neurotransmitters ................................................................................. 313 Protective Properties .............................................................................................. 314
Glutamate Toxicity ............................................................................................ 314 Oxidative Stress ................................................................................................. 315 Abeta Toxicity ................................................................................................... 315 Hypoxic-Ischemic Brain Injury......................................................................... 315 Nerve Gas Poisoning ......................................................................................... 315 Nerve Growth Factor ......................................................................................... 316
Toxicology ............................................................................................................. 316 Cognition Enhancement ......................................................................................... 316
Preclinical .......................................................................................................... 316 Clinical Trials ......................................................................................................... 317 Discussion of Clinical Trials .................................................................................. 320
Huperzine A (HupA) is an alkaloid originally isolated by Chinese scientists from a Chinese club moss, Huperzia serrata, in 1986 (Liu et al., 1986a). Qian Ceng Ta (the traditional name of the plant) has been used for over 1000 years in China for the treatment of a number of ailments, including contusions, strains, swellings, schizophrenia, myasthenia gravis, and more recently organophosphate poisoning (College, 1985; Liu et al., 1986a; Ma and Gang, 2004; Ma et al., 2007). It acts as a potent, highly specic, and reversible inhibitor of acetylcholinesterase (AChE) that crosses the blood-brain barrier (Tang et al., 1989; Wang et al., 2006; Zhang et al., 2008). HupA is similar or superior in potency and duration of AChE inhibition to the AChEIs physostigmine, galantamine, donepezil, and tacrine; the latter three were approved for the treatment of Alzheimer’s disease (AD) in the United States and some European countries (Saxena et al., 1994; Rocha et al., 1998; Lallement et al., 2002b; Gordon et al., 2005; Liu and Sun, 2005; Eckert et al., 2006).
