Xiaoqiang Ma

The Lycopodium alkaloids

Lycopodium alkaloids are quinolizine, or pyridine and alpha-pyridone type alkaloids. Some Lycopodium alkaloids are potent inhibitors of acetylcholinesterase (AChE). Huperzine A (HupA) is reported to increase efficiency for learning and memory in animals, and it shows promise in the treatment of Alzheimers disease (AD). 201 Lycopodium alkaloids from 54 species of Lycopodium (sensu lato) have been reported so far. This review is intended to to cover the chemical, pharmacological and clinical research on Lycopodium alkaloids reported in the literature from the spring of 1993 to August 2004. Structures of 81 new Lycopodium alkaloids are presented, classified and analyzed. The structural characters and biogenetic relationships of the four major Lycopodium alkaloid groups (lycopodine, lycodine, fawcettimine and miscellaneous) are discussed. Bioactivities of Lycopodium alkaloids, especially HupA, are summarized. In particular, the effect of HupA and other cholinesterase inhibitors (anti-AD drugs) on acetylcholine esterase (AChE) activity in the rat cortex and butylcholine esterase activity are compared. Structure-activity relationships and structure modifications of HupA and its analogs are described. Information on clinical trials with HupA and its derivative ZT-1 is presented. The state of HupA availability and recent advances in in vitro propagation of HupA producing plants are outlined. Finally, hypotheses about Lycopodium alkaloid biosynthetic pathways are discussed.

In vitro production of huperzine A, a promising drug candidate for Alzheimer’s disease

Alzheimers disease (AD) is growing in impact on human health. With no known cure, AD is one of the most expensive diseases in the world to treat. Huperzine A (HupA), a anti-AD drug candidate from the traditional Chinese medicine Qian Ceng Ta (Huperzia serrata), has been shown to be a powerful and selective inhibitor of acetylcholinesterase and has attracted widespread attention because of its unique pharmacological activities and low toxicity. As a result, HupA is becoming an important lead compound for drugs to treat AD. HupA is obtained naturally from very limited and slowly growing natural resources, members of the Huperziaceae. Unfortunately, the content of HupA is very low in the raw plant material. This has led to strong interest in developing sources of HupA. We have developed a method to propagate in vitro tissues of Phlegmariurus squarrosus, a member of the Huperziaceae, that produce high levels of HupA. The in vitro propagated tissues produce even higher levels of HupA than the natural plant, and may represent an excellent source for HupA.

Ginger and turmeric expressed sequence tags identify signature genes for rhizome identity and development and the biosynthesis of curcuminoids, gingerols and terpenoids

BackgroundGinger (Zingiber officinale) and turmeric (Curcuma longa) accumulate important pharmacologically active metabolites at high levels in their rhizomes. Despite their importance, relatively little is known regarding gene expression in the rhizomes of ginger and turmeric.ResultsIn order to identify rhizome-enriched genes and genes encoding specialized metabolism enzymes and pathway regulators, we evaluated an assembled collection of expressed sequence tags (ESTs) from eight different ginger and turmeric tissues. Comparisons to publicly available sorghum rhizome ESTs revealed a total of 777 gene transcripts expressed in ginger/turmeric and sorghum rhizomes but apparently absent from other tissues. The list of rhizome-specific transcripts was enriched for genes associated with regulation of tissue growth, development, and transcription. In particular, transcripts for ethylene response factors and AUX/IAA proteins appeared to accumulate in patterns mirroring results from previous studies regarding rhizome growth responses to exogenous applications of auxin and ethylene. Thus, these genes may play important roles in defining rhizome growth and development. Additional associations were made for ginger and turmeric rhizome-enriched MADS box transcription factors, their putative rhizome-enriched homologs in sorghum, and rhizomatous QTLs in rice. Additionally, analysis of both primary and specialized metabolism genes indicates that ginger and turmeric rhizomes are primarily devoted to the utilization of leaf supplied sucrose for the production and/or storage of specialized metabolites associated with the phenylpropanoid pathway and putative type III polyketide synthase gene products. This finding reinforces earlier hypotheses predicting roles of this enzyme class in the production of curcuminoids and gingerols.ConclusionA significant set of genes were found to be exclusively or preferentially expressed in the rhizome of ginger and turmeric. Specific transcription factors and other regulatory genes were found that were common to the two species and that are excellent candidates for involvement in rhizome growth, differentiation and development. Large classes of enzymes involved in specialized metabolism were also found to have apparent tissue-specific expression, suggesting that gene expression itself may play an important role in regulating metabolite production in these plants.

Two Novel Lycopodium Alkaloids from Huperzia serrata

Huperzine Q (1) and N-oxyhuperzine Q (2), two novel irregular fawcettimine-type Lycopodium alkaloids were isolated from the CHCl3 fraction of the basic material of the whole plant of the Chinese medicinal herb Huperzia serrata. Their structures were determined as 13-epi-13β,16-epoxydihydrofawcettimine (1) and N-oxy-13-epi-13β,16-epoxydihydrofawcettimine (2) by means of spectroscopic studies and X-ray crystallographic analysis.

Modules of co-regulated metabolites in turmeric (Curcuma longa) rhizome suggest the existence of biosynthetic modules in plant specialized metabolism

Turmeric is an excellent example of a plant that produces large numbers of metabolites from diverse metabolic pathways or networks. It is hypothesized that these metabolic pathways or networks contain biosynthetic modules, which lead to the formation of metabolite modules—groups of metabolites whose production is co-regulated and biosynthetically linked. To test whether such co-regulated metabolite modules do exist in this plant, metabolic profiling analysis was performed on turmeric rhizome samples that were collected from 16 different growth and development treatments, which had significant impacts on the levels of 249 volatile and non-volatile metabolites that were detected. Importantly, one of the many co-regulated metabolite modules that were indeed readily detected in this analysis contained the three major curcuminoids, whereas many other structurally related diarylheptanoids belonged to separate metabolite modules, as did groups of terpenoids. The existence of these co-regulated metabolite modules supported the hypothesis that the 3-methoxyl groups on the aromatic rings of the curcuminoids are formed before the formation of the heptanoid backbone during the biosynthesis of curcumin and also suggested the involvement of multiple polyketide synthases with different substrate selectivities in the formation of the array of diarylheptanoids detected in turmeric. Similar conclusions about terpenoid biosynthesis could also be made. Thus, discovery and analysis of metabolite modules can be a powerful predictive tool in efforts to understand metabolism in plants.

Three new Phlegmariurine B type lycopodium alkaloids from Huperzia serrata

Phlegmariurine B ( 1 ), a known alkaloid, along with three new analogous compounds, 2 f -hydroxyphlegmariurine B ( 2 ), 2-oxoyphlegmariurine B ( 3 ) and 11-oxophlegmariurine B ( 4 ), were isolated from the CHCl 3 fraction of total alkaloids of whole plant of the Chinese medicinal herb Huperzia serrata . Their structures were elucidated by spectral analysis.

Three new hydroxylated serratidine alkaloids from Huperzia serrata.

A known compound, serratidine ( 1 ), along with three hydroxylated serratidine alkaloids, 6 f -hydroxyserratidine ( 2 ), 4 f -hydroxyserratidine ( 3 ) and 4 f ,6 f -dihydroxyserratidine ( 4 ) were isolated from the CHCl 3 fraction of basic materials of whole plant of the Chinese medicinal herb Huperzia serrata . The relative configurations of the above compounds were determined based on 2D NMR studies.

Ginger and Turmeric Ancient Spices and Modern Medicines

Ginger and turmeric have been used in human cuisine and in traditional medicinal practice for thousands of years. They are widely popular spices used extensively in Asian cuisine and growing in use in western cuisine. They have been used as medicinal plants, due to their anti-inflammatory properties, to treat a wide array of illnesses and conditions, such as arthritis (osteo and rheumatoid), inflammatory bowel disease, cancer, Alzheimer’s disease, the common cold, etc. Two groups of compounds, the diarylheptanoids (including the curcuminoids) and the gingerolrelated compounds, are potent anti-inflammatory compounds and contribute to, or are responsible for, many of the medicinal properties in these plants. They also contribute to the color of turmeric used in curries and to the pungency of ginger. Several of these compounds, most notably curcumin and [6]-gingerol, are now the targets of drug development. Despite their great medicinal and culinary importance, very little basic scientific research has been done on these plants. This is now changing.Belonging to the ingiberaceae, they are members of the Zingiberales. The closest relative to this large group of plants that has been studied in some detail is banana (Musa spp, see chapter in this book), although that plant is not that closely related. The relationships of these plants to other plant groups, their diversity, their production, and recent and proposed efforts to understand the genetic and genomic makeup of these plants are discussed.