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

Halver J, Wenzel K, Sendker J, Carillo Garcia C, Erdelmeier CAJ, Willems E, Mercola M, Symma N, Könemann S, Koch E, Hensel A, Schade D

Abstract

Extracts from the leaves and flowers of Crataegus spp. (i.e., hawthorn species) havebeen traditionally used with documented preclinical and clinical activities in cardiovascularmedicine. Based on reported positive effects on heart muscle after ischemic injury andthe overall cardioprotective profile, the present study addressed potential contributions ofCrataegus extracts to cardiopoietic differentiation from stem cells. The quantified Crataegusextract WS®1442 stimulated cardiomyogenesis from murine and human embryonicstem cells (ESCs). Mechanistically, this effect was found to be induced by promotingdifferentiation of cardiovascular progenitor cell populations but not by proliferation.Bioassay-guided fractionation, phytochemical and analytical profiling suggested highmolecularweight ingredients as the active principle with at least part of the activity dueto 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 distinctdevelopmental pathways, including the upregulation of brain-derived neurotrophic factor(BDNF) and retinoic acid as well as the inhibition of transforming growth factor β/bonemorphogenetic protein (TGFβ/BMP) and fibroblast growth factor (FGF) signaling. Inaddition, WS®1442 stimulated angiogenesis ex vivo in Sca-1+ progenitor cells from adultmice hearts. These in vitro data provide evidence for a differentiation promoting activityof WS®1442 on distinct cardiovascular stem/progenitor cells that could be valuable fortherapeutic heart regeneration after myocardial infarction. However, the in vivo relevanceof this new pharmacological activity of Crataegus spp. remains to be investigated andactive ingredients from bioactive fractions will have to be further characterized.