Bioactive Natural Products and Their Structure–Activity Relationships Studies
Ahindra Nag in Asymmetric Synthesis of Drugs and Natural Products, 2018
The field of natural products has generated a significant and growing number of compounds with promising biomedical activities. 1 Recent estimates indicate that ca. 60% of antitumor and anti-infective agents that are commercially available on the market are of natural product origin and 25% of them are of plant origin. 2–5 Plants are a rich source of lead bioactive compounds, and less than 5% of medicinally important plants have been chemically investigated. 6–7 Ethnomedicinally important plants have shown a 74% success rate in discovering plant-based pharmaceuticals compared to other approaches of plant selections including previously reported bioactivities, bioinformatic, and phylogenetic approaches. 6–7 Enzymes are necessary for human life in mediating/regulating biochemical processes including metabolism, catabolism, cellular signal transduction, and cell cycling and development. Malfunctioning in these biochemical systems leads to diseases that are caused by the dysfunction of enzymes as well as overexpression or hyperactivation of enzymes involved. 8 An understanding of diseases at the molecular level has led to the discovery of effective enzyme inhibitors that are used in clinical practice. For instance, huperzine A, one of the potent acetylcholinesterase inhibitors, is a prescribed drug for the treatment of Alzheimer’s disease. 9 Our recent phytochemical studies on medicinally important plants have resulted in the isolation of novel natural products exhibiting various potent bioactivities that are summarized as follows.
Huperzine A as a neuroprotective and antiepileptic drug: a review of preclinical research
Published in Expert Review of Neurotherapeutics, 2016
U. Damar, R. Gersner, J. T. Johnstone, S. Schachter, A. Rotenberg
Huperzine A (HupA) is an acetylcholinesterase (AChE) inhibitor extracted from Huperzia Serrata, a firmoss, which has been used for various diseases in traditional Chinese medicine for fever and inflammation. More recently, it has been used in Alzheimer’s disease and other forms of dementia with a presumed mechanism of action via central nicotinic and muscarinic receptors. HupA is marketed as a dietary supplement in the U.S. This article reviews newly proposed neuroprotective and anticonvulsant HupA properties based on animal studies. HupA exerts its effects mainly via α7nAChRs and α4β2nAChRs, thereby producing a potent anti-inflammatory response by decreasing IL-1β, TNF-α protein expression, and suppressing transcriptional activation of NF-κB signaling. Thus, it provides protection from excitotoxicity and neuronal death as well as increase in GABAergic transmission associated with anticonvulsant activity.
An update on huperzine A as a treatment for Alzheimer's disease
Published in Expert Opinion on Investigational Drugs, 2008
John T Little, Sally Walsh, Paul S Aisen
Huperzine A is a natural cholinesterase inhibitor derived from the Chinese herb Huperzia serrata. There is evidence that huperzine A may compare favorably in symptomatic efficacy to cholinesterase inhibitors in use. In addition, huperzine A has antioxidant and neuroprotective properties that suggest that it may be useful as a disease-modifying treatment for Alzheimer's disease (AD). The drug is available as a nutriceutical in the US. However, there have been no published controlled clinical trials outside China assessing its toxicity and efficacy. This paper reviews the development of huperzine A as a treatment for AD, including the Phase II trial now under way in the US.
The scoop on brain health dietary supplement products containing huperzine A
Published in Clinical Toxicology, 2020
Cindy Crawford, Yan-Hong Wang, Bharathi Avula, Ji-Yeong Bae, Ikhlas A. Khan, Patricia A. Deuster
Context: Public health concerns are emerging surrounding huperzine A commonly found in dietary supplements. We sought to determine the actual content of products claiming to contain huperzine A and whether the ingredients on the supplement facts labels matched the analyses. Methods: We identified and analyzed 22 dietary supplement products listing huperzine A on product labels. We found these products were listed in Natural Medicines and Dietary Supplement Databases and being queried by Military Service Members for enhanced mental focus, alertness and energy. Analyses were conducted by using Liquid Chromatography-Quadrupole Time of Flight Mass Spectrometry. Results: Sixteen (73%) products had at least one ingredient claimed on the supplement facts label not detected through analysis. Compounds not reported on the label were detected in 16 (73%) products analyzed. Nine products (41%) listed ingredients not meeting the regulations for being a dietary supplement ingredient according to the FDA. Ingredients of most concern detected include stimulants: demelverine, 1,5-dimethylhexylamine, 1,3-dimethylhexylamine, N-phenethyl dimethylamine, halostachine, higenamine, noopept, β-PEA, vinpocetine, sulbutiamine; and hordenine, currently on the FDA advisory list. Quantitative analysis showed the presence of huperzine A in the range from detected under the limits of quantification (DUL) to 267.1 µg/serving. Only two supplements showed huperzine A content within 10% of the declared amount. Conclusions: In a study of dietary supplements claiming to contain huperzine A, we found products that had at least one ingredient claimed on the supplement facts label not detected through analysis. Moreover, some ingredients not on the label could be dangerous and likely do not meet the definition of a dietary supplement ingredient according to the FDA. Quantitative analysis of huperzine A showed the amount detected was not in line with what appeared on the product label. Consumers should be aware of deceptive label claims and warned not to purchase products containing potentially dangerous ingredients.
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- Alzheimer's Disease