Occurrence of N-phenylpropenoyl-L-amino acid amides in different herbal drugs and their influence on human keratinocytes, on human liver cells and on adhesion of Helicobacter pylori to the human stomach.
Thirty commonly used medicinal plants were screened by a selective and specific LC-MS/MS method for the occurrence of N-phenylpropenoyl- L-amino acid amides, a new homologous class of secondary products. In 15 plants, one or more of the respective derivatives (1 to 12) were found and quantitated. Especially roots from Angelica archangelica, fruits of Cassia angustifolia, C. senna, Coriandrum sativum, leaves from Hedera helix, flowers from Lavandula spec. and from Sambucus nigra contained high amounts (1 to 11 microg/g) of mixtures of the different amides 1 to 12. For functional investigations on potential activity in cellular physiology, two amides with an aliphatic (8) and an aromatic amino acid residue (5) were used. N-(E)-Caffeic acid L-aspartic acid amide (8) and N-(E)-caffeic acid L-tryptophan amide (5) stimulated mitochondrial activity as well as the proliferation rate of human liver cells (HepG2) at 10 microg/mL significantly. When monitoring the influence of selected phase I and II metabolizing enzymes, both compounds did not influence CYP3A4 gene expression, but stimulated CYP1A2 gene expression and inhibited GST expression. Also, the proliferation of human keratinocytes (NHK) was increased up to 150% by both amides 5 and 8; this stimulation was also detectable on the level of gene expression by an up-regulation of the transcription factor STAT6. The aliphatic aspartic compound 8 showed strong antiadhesive properties on the adhesion of Helicobacter pylori to human stomach tissue.
Hensel
A
A
University of Münster, Institute for Pharmaceutical Biology and Phytochemistry, Münster, Germany. ahensel@uni-muenster.de
Deters
A M
AM
Müller
G
G
Stark
T
T
Wittschier
N
N
Hofmann
T
T
D000577:Amides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000596:Amino Acids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D001422:Bacterial Adhesion / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002853:Chromatography, Liquid; D005786:Gene Expression Regulation / Q000187:drug effects; D016480:Helicobacter pylori / Q000187:drug effects* / Q000472:pathogenicity; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D013058:Mass Spectrometry; D010946:Plants, Medicinal / Q000737:chemistry*; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013270:Stomach / Q000187:drug effects / Q000382:microbiology*
D000577:Amides; D000596:Amino Acids; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human