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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.01357

Crataegus Extract WS®1442 Stimulates Cardiomyogenesis and Angiogenesis From Stem Cells: A Possible New Pharmacology for Hawthorn?

Jonas Halver1,  Kristin Wenzel2, Jandirk Sendker3,  Carmen Carrillo Garcia4, Clemens A. Erdelmeier5, Erik Willems6,  Mark Mercola6,  Nico Symma3, Stephanie Köneman2,  Egon Koch5,  Andreas Hensel3 and  Dennis Schade1, 7, 8*
  • 1Faculty of Chemistry and Chemical Biology, Technical University Dortmund, Germany
  • 2Partner Site Greifswald, German Centre for Cardiovascular Research (DZHK), Germany
  • 3Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Germany
  • 4Pharmaceutical Institute, Faculty of Mathematics and Natural Sciences, Christian-Albrechts-Universität zu Kiel, Germany
  • 5Dr. Willmar Schwabe GmbH & Co. KG, Germany
  • 6Sanford Burnham Prebys Medical Discovery Institute, United States
  • 7University of Kiel, Germany
  • 8Partner site Hamburg/Kiel/Lübeck, DZHK, German Centre for Cardiovascular Research, Germany

Extracts from the leaves and flowers of Crataegus spp. (i.e., hawthorn species) have been traditionally used with documented preclinical and clinical activities in cardiovascular medicine. Based on reported positive effects on heart muscle after ischemic injury and the overall cardioprotective profile, the present study addressed potential contributions of Crataegus extracts to cardiopoietic differentiation from stem cells.
The quantified Crataegus extract WS®1442 stimulated cardiomyogenesis from murine and human embryonic stem cells (ESCs). Mechanistically, this effect was found to be induced by promoting differentiation of cardiovascular progenitor cell populations but not by proliferation. Bioassay-guided fractionation, phytochemical and analytical profiling suggested high-molecular weight ingredients as the active principle with at least part of the activity due to oligomeric procyanidines (OPCs) with a degree of polymerization between 3 and 6 (DP3-6). Transcriptome profiling in mESCs suggested two main, plausible mechanisms: These were early, stress-associated cellular events along with the modulation of distinct developmental pathways, including the upregulation of brain-derived neurotrophic factor (BDNF) and retinoic acid as well as the inhibition of Transforming Growth Factor /Bone Morphogenetic Protein (TGF/BMP) and Fibroblast Growth Factor (FGF) signaling. In addition, WS®1442 stimulated angiogenesis ex vivo in Sca-1+ progenitor cells from adult mice hearts.
These in vitro data provide evidence for a differentiation promoting activity of WS®1442 on distinct cardiovascular stem/progenitor cells that could be valuable for therapeutic heart regeneration after myocardial infarction. However, the in vivo relevance of this new pharmacological activity of Crataegus spp. remains to be investigated and active ingredients from bioactive fractions will have to be further characterized.

Keywords: Crataegus spp., Regenerative Medicine, Stem Cells, Angiogenesis, Oligomeric proanthocyanidines, Cardiomyogenic differentiation, bioassay-guided fractionation

Received: 05 Jul 2019; Accepted: 25 Oct 2019.

Copyright: © 2019 Halver, Wenzel, Sendker, Carrillo Garcia, Erdelmeier, Willems, Mercola, Symma, Köneman, Koch, Hensel and Schade. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Dennis Schade, University of Kiel, Kiel, Germany, schade@pharmazie.uni-kiel.de