On the background of evidence-based positive effects of hawthorn on cardiac muscles, the effect of a standardized special extract on cardiac progenitor cells was investigated in an in vitro study. Stimulation of cardiomyogenesis was detected in both murine and human embryonic stem cells.
Hawthorn, lat. Crataegus, is a traditionally used medicinal plant whose extract WS®1442has been intensively studied phytochemically, pharmacologically and clinically [1]. The use of hawthorn for symptomatic treatment of cardiovascular disease is an evidence-based phytopharmacological therapeutic option. In addition, cardioprotective effects have been described in various in vitro and in vivo infarct models [2].
Cardioprotective effect proven
Cardiplant® 450 (WS®1442) [3] is recommended in Switzerland for the indication of functional cardiac complaints (rapid pulse, palpitations, palpitations, dizziness, feeling of pressure and tightness in the heart area) and is on the health insurance company’s list of specialties for this indication. According to the US Food and Drug Administration, Hawthorn extract can also be used as an add-on for mild and moderate NYHA chronic heart failure [4]. Antioxidant, antiatherosclerotic, and vasodilator effects of hawthorn extract have been scientifically proven [5]. The pharmacologically relevant constituents are, on the one hand, flavonoids, representatives of polyphenols, which are associated, among others, with reduced platelet activity, enzymatic modulation, anti-inflammatory effects and blood pressure lowering [6]. On the other hand, oligomeric procyanidins (OPC), also polyphenols, have a strong antioxidant effect [7], keeping blood vessels elastic, protecting them from deposits and preserving them from future oxidative damage by free radicals.
Cardiomyogenesis demonstrated in vitro
Whereas the adult heart was previously thought to be terminally differentiated, more recent research indicates that the heart has a regenerative capacity, albeit small, beyond the neonatal period [8,9]. To investigate whether a regenerative effect component can possibly also be described for hawthorn, the effect of the hawthorn special extract WS®1442on cardiac progenitor cells was investigated in vitro. In the study published in 2019 by Halver et al. WS®1442was tested in stem cell-based assay systems, with stimulation of cardiomyogenesis detected in both murine and human embryonic stem cells [10]. This effect induced by Crataegus extract WS®1442in human and murine embryonic stem cells is empirical evidence that WS®1442promotes differentiation of various cardiovascular stem/progenitor cells relevant for therapeutic regeneration of myocardium after myocardial infarction. By analysis using extract fractions and reference substances, cardiogenic activity could be assigned to high molecular weight ingredients. The OPC-rich fractions ultraretentate, MeOH, and acetone eluates were found to promote cardiogenesis in a dose-dependent manner.
Mechanisms of action identified
One explanation for the cardiomyogenic activity of WS®1442is that it promotes the differentiation of cardiovascular progenitor cells (Fig. 1). According to the transcriptome profile, upregulation of the growth factor BDNF* and retinoic acid as well as inhibition of the TGFbeta**/BMP*** and FGF§ signalingpathways are involved in cardiogenic mechanisms. The study of human and murine pluripotent embryonic stem cells is an in vitro model system in which, among other things, the regulation of signaling pathways and gene expression during development can be studied. Translation to the in vivo situation would mean an expansion of the spectrum of activity of the traditionally used hawthorn extracts. The focus of appropriate studies should be on the investigation of cardiogenic effects under physiological conditions and after an ischemic episode [10].
* BDNF (brain-derived neurotrophic factor) = neurotrophic growth factor
** TGFbeta (transforming growth factor-beta) = transforming growth factor beta
*** BMP (bone morphogenetic protein) = bone-forming protein
§ FGF (fibroblast growth factor) = fibroblast growth factor
Source: Schwabe Pharma AG
Literature:
- Koch E, Malek FA: Standardized extracts from hawthorn leaves and flowers in the treatment of cardiovascular disorders–preclinical and clinical studies. Planta Med 2011; 77; 1123-1128.
- Wang J, Xiong X, Feng B: Effect of crataegus usage in cardiovascular disease prevention: an evidence-based approach. Evid Based Complement Alternat Med 2013; 2013: 149363.
- Swiss Drug Compendium: Cardiplant® 450, https://compendium.ch, last accessed 13.02.2020.
- FDA: U.S. Food and Drug Administration. www.fda.gov, last accessed Feb. 13, 2020.
- Orhan IE: Phytochemical and Pharmacological Activity Profile of Crataegus oxyacantha L. (Hawthorn) – A Cardiotonic Herb. Curr Med Chem 2018; 25(37): 4854-4865.
- Cory H, et al: The Role of Polyphenols in Human Health and Food Systems: A Mini-Review. Frontiers in Nutrition 2018, 5 DOI: 10.3389/fnut.2018.00087.
- Zorniak M, Szydlo B, Krzeminski TF: Crataegus special extract WS® 1442: up-to-date review of experimental and clinical experiences. J Physiol Pharmacol 2017; 68(4): 521-526.
- Bergmann O, et al: Evidence for cardiomyocyte renewal in humans. Science 2009; 324: 98-102.
- Mollova M, et al: Cardiomyocyte proliferation contributes to heart growth in young humans. Proc Natl Acad Sci U.S.A. 2013; 110: 1446-1451.
- Halver J, et al: Crataegus Extract WS®1442Stimulates Cardiomyogenesis and Angiogenesis From Stem Cells: A Possible New Pharmacology for Hawthorn? Front. Pharmacol., Nov. 27, 2019, https://doi.org/10.3389/fphar.2019.01357
HAUSARZT PRAXIS 2020; 15(3): 27
