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HPLC-Based Activity Profiling for GABAA Receptor Modulators in Searsia pyroides Using a Larval Zebrafish Locomotor Assay.

  • Moradi-Afrapoli F Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
  • van der Merwe H Faculty of Natural and Agricultural Sciences, University of the Free State, Bloemfontein, Republic of South Africa.
  • De Mieri M Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
  • Wilhelm A Faculty of Natural and Agricultural Sciences, University of the Free State, Bloemfontein, Republic of South Africa.
  • Stadler M Institute of Pharmacology and Toxicology, Pharmaziezentrum, University of Vienna, Vienna, Austria.
  • Zietsman PC National Museum, Bloemfontein, Republic of South Africa.
  • Hering S Institute of Pharmacology and Toxicology, Pharmaziezentrum, University of Vienna, Vienna, Austria.
  • Swart K Faculty of Natural and Agricultural Sciences, University of the Free State, Bloemfontein, Republic of South Africa.
  • Hamburger M Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
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  • 2017-05-17
Published in:
  • Planta medica. - 2017
Anacardiaceae
Anacardic Acids
Animals
Biological Assay
Chlorides
Chromatography, High Pressure Liquid
GABA Agents
Larva
Locomotion
Methylene Chloride
Oocytes
Pentylenetetrazole
Plant Extracts
Plant Leaves
Receptors, GABA-A
Xenopus laevis
Zebrafish
gamma-Aminobutyric Acid
English A dichloromethane extract from leaves of Searsia pyroides potentiated gamma aminobutyric acid-induced chloride currents by 171.8 ± 54% when tested at 100 µg/mL in Xenopus oocytes transiently expressing gamma aminobutyric acid type A receptors composed of α1β2γ2s subunits. In zebrafish larvae, the extract significantly lowered pentylenetetrazol-provoked locomotion when tested at 4 µg/mL. Active compounds of the extract were tracked with the aid of HPLC-based activity profiling utilizing a previously validated zebrafish larval locomotor activity assay. From two active HPLC fractions, compounds 1 - 3 were isolated. Structurally related compounds 4 - 6 were purified from a later eluting inactive HPLC fraction. With the aid of 1H and 13C NMR and high-resolution mass spectrometry, compounds 1 - 6 were identified as analogues of anacardic acid. Compounds 1 - 3 led to a concentration-dependent decrease of pentylenetetrazol-provoked locomotion in the zebrafish larvae model, while 4 - 6 were inactive. Compounds 1 - 3 enhanced gamma aminobutyric acid-induced chloride currents in Xenopus oocytes in a concentration-dependent manner, while 4 - 6 only showed marginal enhancements of gamma aminobutyric acid-induced chloride currents. Compounds 2, 3, and 5 have not been reported previously.
Language
  • English
Open access status
green
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Persistent URL
https://sonar.ch/global/documents/252603
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