期刊
PHYTOCHEMICAL ANALYSIS
卷 24, 期 2, 页码 141-147出版社
WILEY
DOI: 10.1002/pca.2393
关键词
high-resolution bioassay; HPLC-SPE-NMR; depression; clorgyline; monoamine oxidase-A; piperine; Piper nigrum
资金
- Fundacao para a Ciencia e a Tecnologia [SFRH/BPD/63922/2009]
- Carlsberg Foundation
- National Institute on Minority Health and Health Disparities [P20MD006738, G12MD007582] Funding Source: NIH RePORTER
Introduction - Depression is a mental disease causing large personal and socio-economic problems, and new improved drugs are therefore needed. Selective monoamine oxidase A (MAO-A) inhibitors are potential anti-depressants, but discovering new MAO-A inhibitors from natural sources by bioassay-guided approaches are a lengthy and time-consuming process. New analytical technologies that allow simultaneously chemical and biological screening of extracts are therefore urgently needed. Method - In the present study we describe coupling of a photometric microplate-based high-resolution MAO-A inhibitor assay with a hyphenated system consisting of high-performance liquid chromatography, solid-phase extraction and tube transfer nuclear magnetic resonance (HPLC-SPE-ttNMR). The standard compound clorgyline, and an extract of black pepper (Piper nigrum L.), representing a complex plant matrix, were used for proof-of-concept. Results - The work with clorgyline showed that the microplate-based high-resolution assay produced MAO-A inhibition profiles that easily allowed detection of submicrogram amounts of this selective MAO-A inhibitor. Furthermore, the HPLC-SPE-ttNMR/high-resolution MAO-A inhibition assay platform allowed identification of piperine and two piperine analogues as the main MAO-A inhibitors in the black pepper petroleum ether extract. Conclusion - The HPLC-SPE-ttNMR/high-resolution MAO-A inhibition assay platform is a powerful tool for fast and efficient identification of new MAO-A inhibitors from complex extracts, and promise future advancement in the search for new antidepressants from natural sources. Copyright (C) 2012 John Wiley & Sons, Ltd.
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