HPLC-based bioactivity profiling of plant extracts: a kinetic assay for the identification of monoamine oxidase-A inhibitors using human recombinant monoamine oxidase-A.

An assay for the HPLC-based search for monoamine oxidase-A (MAO-A) inhibitors in plant extracts was established. It combines human recombinant MAO-A, expressed as GST-fusion protein in yeast, with a kinetic measurement of the conversion of kynuramine to 4-hydroxyquinoline. Substrate selectivity and kinetic parameters of the GST-fusion protein were comparable to the wild-type enzyme. The applicability of the assay to HPLC-based activity profiling was tested with plant extracts spiked with small amounts of known MAO inhibitors.

[1]  J. Shih,et al.  Effects of Carboxyl-terminal Truncations on the Activity and Solubility of Human Monoamine Oxidase B* , 2001, The Journal of Biological Chemistry.

[2]  M. Hamburger,et al.  Novel tetramic acids and pyridone alkaloids, militarinones B, C, and D, from the insect pathogenic fungus Paecilomyces militaris. , 2003, Journal of natural products.

[3]  C. Abell,et al.  Molecular characterization of monoamine oxidases A and B. , 2001, Progress in nucleic acid research and molecular biology.

[4]  B. Testa,et al.  Monoamine oxidase inhibitory activity of some Hypericum species native to South Brazil , 2001, The Journal of pharmacy and pharmacology.

[5]  W. Günther,et al.  Militarinone A, a neurotrophic pyridone alkaloid from Paecilomyces militaris. , 2002, Organic letters.

[6]  M. Palcic,et al.  A continuous spectrophotometric assay for monoamine oxidase and related enzymes in tissue homogenates. , 1997, Analytical biochemistry.

[7]  M. Hamburger,et al.  Screening of entomopathogenic Deuteromycetes for activities on targets involved in degenerative diseases of the central nervous system. , 2003, Journal of ethnopharmacology.

[8]  S. Ryu,et al.  Antioxidant activity of resveratrol closely correlates with its monoamine oxidase-A inhibitory activity , 1990 .

[9]  P. Seeburg,et al.  cDNA cloning of human liver monoamine oxidase A and B: molecular basis of differences in enzymatic properties. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[10]  A. Schurr,et al.  Cannabis extract, but not delta 1-tetrahydrocannabinol, inhibits human brain and liver monoamine oxidase. , 1984, General pharmacology.

[11]  H. Irth,et al.  Analytical tools for the detection and characterization of biologically active compounds from nature , 2002, Phytochemistry Reviews.

[12]  M Mandel,et al.  Calcium-dependent bacteriophage DNA infection. , 1970, Journal of molecular biology.

[13]  L. Oreland,et al.  Characterization and partial purification of human monoamine oxidase-B expressed in Escherichia coli. , 1996, Protein expression and purification.

[14]  R. Deschenes,et al.  Vectors for the inducible overexpression of glutathione S‐transferase fusion proteins in yeast , 1993, Yeast.

[15]  W. Weyler,et al.  Differences in substrate specificities of monoamine oxidase A from human liver and placenta. , 1991, Biochemical and biophysical research communications.

[16]  H. Weissbach,et al.  A rapid spectrophotometric assay of mono-amine oxidase based on the rate of disappearance of kynuramine. , 1960, The Journal of biological chemistry.

[17]  W. Weyler,et al.  Purification and properties of mitochondrial monoamine oxidase type A from human placenta. , 1985, The Journal of biological chemistry.

[18]  M. Hamburger,et al.  Identification and isolation of the cyclooxygenase-2 inhibitory principle in Isatis tinctoria. , 2001, Planta medica.

[19]  H. Wagner,et al.  Inhibition of type A and type B monoamine oxidases by naturally occurring xanthones. , 1981, Planta medica.

[20]  J. Shih,et al.  Monoamine oxidase: from genes to behavior. , 1999, Annual review of neuroscience.

[21]  D J Newman,et al.  The influence of natural products upon drug discovery. , 2000, Natural product reports.

[22]  P. Riederer,et al.  MAO-B inhibitors: multiple roles in the therapy of neurodegenerative disorders? , 2000, Parkinsonism & related disorders.

[23]  A. Dar,et al.  Behavioral and Biochemical Studies of Dichloromethane Fraction From the Areca catechu Nut , 2000, Pharmacology Biochemistry and Behavior.

[24]  D. Mckenna,et al.  Monoamine oxidase inhibitors in South American hallucinogenic plants: tryptamine and beta-carboline constituents of ayahuasca. , 1984, Journal of ethnopharmacology.

[25]  J. Daly,et al.  Bioassay-guided isolation of epiquinamide, a novel quinolizidine alkaloid and nicotinic agonist from an Ecuadoran poison frog, Epipedobates tricolor. , 2003, Journal of natural products.

[26]  D. Edmondson,et al.  High-level expression of human liver monoamine oxidase B in Pichia pastoris. , 2000, Protein expression and purification.

[27]  P. Carrupt,et al.  Natural and Synthetic Xanthones as Monoamine Oxidase Inhibitors: Biological Assay and 3D‐QSAR , 2001 .

[28]  D. Edmondson,et al.  High-level expression of human liver monoamine oxidase A in Pichia pastoris: comparison with the enzyme expressed in Saccharomyces cerevisiae. , 2002, Protein expression and purification.

[29]  D. Pompon,et al.  Comparative membrane locations and activities of human monoamine oxidases expressed in yeast , 1991, FEBS letters.

[30]  A. Khalil,et al.  Isolation and characterization of a monoamine oxidase inhibitor from tobacco leaves. , 2000, Chemical research in toxicology.

[31]  M. Hamburger,et al.  Pressurized liquid extraction of medicinal plants. , 1999, Journal of chromatography. A.

[32]  Z. D. Sharp,et al.  A general method for polyethylene-glycol-induced genetic transformation of bacteria and yeast. , 1983, Gene.

[33]  K. Hostettmann,et al.  7. Bioactivity in plants: the link between phytochemistry and medicine , 1991 .

[34]  J. Salach Monoamine oxidase from beef liver mitochondria: simplified isolation procedure, properties, and determination of its cysteinyl flavin content. , 1979, Archives of biochemistry and biophysics.

[35]  J. Wouters,et al.  Structural aspects of monoamine oxidase and its reversible inhibition. , 1998, Current medicinal chemistry.