Huperzia Huperzine

Traditionally, plants are a rich source of AChE inhibitors. People from the Caucasus used bulbs of snowdrops Galanthus sp.) to treat forgetfulness [25]. The active compound in this plant has been isolated and called galanthamine. Other plant-derived AChE inhibitors used for treatment of Alzheimer s disease include Huperzine A from Huperzia serrata and Rivastigmine (Excelon). The latter is a derivative from physostigmine isolated from the calabar bean, Physos-tigma vmmosum. 

Acetate is also a precursor of several groups of alkaloids in the form of a polyketide chain that interacts with an unknown nitrogen source (as in the terpene alkaloids). Examples of acetate-derived alkaloids are coniine—the toxic principle of Conium maculatum, pinidine—from several Pinus species, and the naphthy-lisoquinoline alkaloids (e.g., ancistrocladine)—showing antimalarial and anti-HIV activity. The latter alkaloids are apparently derived from the oxidative coupling of two pentaketide units. Huperzine A, currently in clinical trials for the treatment of Alzheimer s disease and isolated from the club moss (Serrata huperzia), is derived from a polyacetate precursor (Fig. 46). 

The impact of Traditional Chinese Medicine on modern western drugs is demonstrated not only by commercialized therapeutic agents such as camptothecin or artemisinin but also by clinical candidates like huperzine A, an acetylcholinesterase inhibitor to treat Alzheimer s disease [103]. Huperzine A can be isolated from both, Huperzia serrata, and H. selago [104,105]. Because huperzine A is produced only at very low levels a synthetic approach has been developed in order to provide sufficient quantities for preclinical toxicology studies and clinical trials. 

Eburnamenine Eburnamine Eburnamonine Geissoschizol Huperzia serrata Huperzine A Hypericum perforatum St. John s Wort Hyperoside... 

Huperzine A, isolated from the Chinese herb Huperzia serrata (Thunb) Trev, is a novel reversible and selective AChE inhibitor. ZT-1 is a novel analog of huperzine A. ZT-1 is a prodrug that is rapidly absorbed and converted into huperzine A, and ZT-1 is well tolerated in healthy Chinese volunteers [173],... 

A myriad of natural compounds have been tested for the past 20 years in a frenetic search for agents with potential effects against AD neuropathology. Some of these compounds include alkaloids from the calabar bean (Physostigma venenosum) huperzine A from Huperzia serrata-, galantamine from the snowdrop Galanthus woronowii cannabinoids (cannabidiol from Cannabis sativa) ... 

More recently, Ben-Hameda et al. (57) used this combination to improve the sensitivity of the determination of Huperzine A (a natural product from Huperzia serrata used to treat Alzheimer s disease and incorporated as a food supplement). BGE concentration (acetate buffer pH = 4.6) and voltage were used as input parameters, while peak area, peak height, or migration time were individually studied as outputs. In each case, optimal ANN architecture was (2 3 1). To maximize the sensitivity, relatively high concentrations of the BGE and low voltages were required (optimum conditions were 50mM sodium acetate and 10kV). 

Huperzine A, a potent anticholinesterase alkaloid, and huperzine B were separated from a Chinese medicinal herb, Huperzia serrata (Thunb) Trev. Lycopodium serratum Thunb.), (Lycopodiaceae), by Liu et al [25]. The plant was used in Zhejiang Province of China for treatment of some mental disorders. 

Chemistry, pharmacology, and clinical efficacy of the Chinese nootropic agent huperzine A, alkaloid from Huperzia serrata with aimulated 2-pyridone and l-amino-3-methyl-9-ethylidenebicyclo[3.3.1]nona-2,6-diene fragments 99ACR641. 

Huperzia serrata Huperzine A Huperzine J Huperzine K Huperzine L Phlegmariurine... 

Human tissue kallikrein (KLK), 3749 Human umbilical vein endothelial cells (HUVEC), 2204, 3216 Humulene, 4116, 4118 120 a-Humulene, 2986 Humulus lupulus, 2986, 4119, 4121 Huntington s diseases, 589, 3488 Huperzia serrata, 1241, 1245, 1338 Huperzines A, 1244, 1338, 1340, 1530-1532 Huperzines B, 1248, 1338... 

Ma X, Tan C, Zhu D, Gang DR, Xiao P (2007) Huperzine A from Huperzia species-an ethnopharmacological review. J Ethnopharmacol 113 15... 

Huperzine, an alkaloid from the plant Huperzia serrata, is a potent and highly selective, reversible acetylcholinesterase inhibitor. 

Huperzine A (HupA) and huperzine B Amberlite XAD-4 V ter and ethanol Huperzia serrata [123]... 

Huperzine A (49) is a sesquiterpene alkaloid isolated from a traditional Chinese herbal remedy, Huperzia serrata ( Qian Ceng Ta ) in 1986 [128], This compound has been proved to be a potent, selective and reversible acetylcholinesterase (AChE) inhibitor, and demonstrated memory enhancement and neuroprotective functions in clinical trials as a therapeutic against Alzheimer s disease (AD) in the People s Republic of China [129, 130], In 2004, a phase II clinical trial focused on its cognitive function was initiated by the National Institute on Aging (NIA) in the United States [131], ZT-1 (50), considered more selective than huperzine A, was developed as a semi-synthetic derivative of 49 by cooperation of the Shanghai Institute of Materia Medica and Debiopharm of Switzerland and is currently... 

On inhibition of the apoptotic pathway, as by the loss of p53 or Apaf-1 function, pre-cancerous cells survive and proliferate, and eventually form a tumor. A number of alkaloids have been described recently that exhibit anti-apoptotic effects. Huperzine A from Huperzia serrata (Lycopodiaceae) blocks apoptosis via the inhibition of ROS formation and caspase-3 activation (48). In the case of sampangine, the apoptotic effects could be blocked by the administration of a... 

This review describes the recent studies on Lycopodium alkaloids isolated from the genus Lycopodium and Huperzia, the proposed biogenetic pathway, and the syntheses of Lycopodium alkaloids based on these biogenetic proposals. In section II, all of the Lycopodium alkaloids isolated so far, and including our recent work, are surveyed, while sections III and IV mainly deal with the biogenetic pathways and the total syntheses of the Lycopodium alkaloids, respectively. In sections V, VI, and VII, pharmacology, total synthesis, and SAR studies, respectively of huperzine A (I) are briefly surveyed. 

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