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  2. Coumarins from Seseli devenyense Simonk.: Isolation by Liquid-Liquid Chromatography and Potential Anxiolytic Activity Using an In Vivo Zebrafish Larvae Model

Coumarins from Seseli devenyense Simonk.: Isolation by Liquid-Liquid Chromatography and Potential Anxiolytic Activity Using an In Vivo Zebrafish Larvae Model

  • Int J Mol Sci. 2021 Feb 12;22(4):1829. doi: 10.3390/ijms22041829.
Jarosław Widelski 1 Simon Vlad Luca 2 3 Adrianna Skiba 4 Monika Maciąg 5 6 Barbara Budzyńska 5 Laurence Marcourt 7 Jean-Luc Wolfender 7 Krystyna Skalicka-Woźniak 4
Affiliations

Affiliations

  • 1 Department of Pharmacognosy with Medicinal Plant Unit, Medical University of Lublin, 20-093 Lublin, Poland.
  • 2 Biothermodynamics, TUM School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.
  • 3 Department of Pharmacognosy, Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania.
  • 4 Independent Laboratory of Natural Products Chemistry, Medical University of Lublin, 20-093 Lublin, Poland.
  • 5 Independent Laboratory of Behavioral Studies, Medical University of Lublin, 20-093 Lublin, Poland.
  • 6 Department of Biopharmacy, Medical University of Lublin, 20-093 Lublin, Poland.
  • 7 School of Pharmaceutical Sciences, Institute of Pharmaceutical Sciences of Western Switzerland, IPSWS, University of Geneva, CMU, 1211 Geneva, Switzerland.
Abstract

Different types of anxiety disorders have become the number one mental health issue in developed countries. The search for new, safer and effective drug-like molecules among naturally derived substances faces two difficulties: an efficient method of isolation compounds with a high-purity and high-throughput animal model for activity assay. Thus, the aim of the present study was to isolate by liquid-liquid chromatography high-purity rare Coumarins from the fruits of Seseli devenyense Simonk. and evaluate their anxiolytic effect (defined as reversed thimotaxis) using a 5-days post-fertilization (dpf) Danio rerio larvae model. Liquid-liquid chromatography enabled the isolation of one simple hydroxycoumarin (devenyol) and four pyranocoumarins (cis-khellactone, d-laserpitin, isolaserpitin and octanoyllomatin). The anxiolytic effect was defined as a decrease in the time spent in the boundaries of the living space (also described as reversed thigmotaxis). Our results show that all isolated courmarins exerted a significant influence on the anxiety behavior (anxiolytic activity) in the zebrafish larvae model. According to our knowledge, this is the first report of anxiolytic activity of pyranocoumarins and devenyol.

Keywords

Apiaceae; Danio rerio; Seseli devenyense; anxiety; central nervous system; countercurrent chromatography.

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