Published July 19, 1994.
List of German Commission E Monographs (Phytotherapy)
Weißdornblätter mit Blüten
Crataegi folium cum flore, hawthorn leaf with flowers.
Hawthorn leaf with flower, consisting of dried flowering twig tips of Crataegus monogyna Jaquin emend. Lindman or C. laevigata (Poiret) de Candolle [Fam. Rosaceae], or other members of the Crataegus genus cited in a valid pharmacopeia as well as preparations from them in an effective dosage.
The drug contains flavonoids (flavones, flavonols) including hyperoside, vitexinrhamnose, rutin, and vitexin and oligomeric procyanidins (n=2 to n=8 catechins and/or epicatechins).
The following pharmacodynamic effects have been established in isolated organs or in animal experimentation with preparations from hawthorn leaf with flower (hydroalcoholic extract with defined content of oligomeric procyanidins and/or flavonoids: macerates, fresh plant extract) and with individual fractions (oligomeric procyanidins, biogenic amines): Positive inotropic effect, positive dromotropic effect, negative bathmotropic effect, increased coronary and myocardial circulatory perfusion, reduction in peripheral vascular resistance.
In cases of cardiac insufficiency according to Stage II New York Heart Association (NYHA), an improvement of subjective findings as well as an increase in cardiac work tolerance, a decrease in pressure/heart rate product, an increase in the ejection fraction and a rise in the anaerobic threshold have been established in human pharmacological studies following the administration of 160 to 900 mg aqueous-alcoholic extract per day (adjusted to oligomeric procyanidins and/or flavonoids) over periods lasting up to 56 days.
The pharmacokinetics of the drug have been investigated only in animal studies, and no scientific results are available in the context of human pharmacokinetics.
Investigations of acute toxicity using a hydroalcoholic dry extract (drug/extract ratio 5:1, standardized for oligomeric procyanidins) are available, according to which no fatal events occurred after oral or peritoneal administration in mice or rats in doses of up to 3 g per kg of body weight.
Symptoms of intoxication with an intraperitoneal administration of 3 g/kg body weight include sedation, piloerection, dyspnea, and tremor.
The oral administration of powdered herb at individual doses of 3 g per kg body weight in rats and 5 g per kg body weight in mice produce no fatal reactions.
No toxic effects were observed after oral administration of 30, 90, and 300 mg aqueous/ethanolic dry extract per kg body weight in rats and dogs over a period of 26 weeks. For this extract, the "no effect" dose was 300 mg per kg body weight in rats and dogs for 26 weeks. No fatal events and no toxic effects were observed after the oral administration of 300 and 600 mg drug powder per kg body weight over a period of four weeks.
No experimental data are available concerning embryonic and fetal toxicity, fertility, and post-natal development.
Although they have indeed produced different results, more recent studies are now available as regards testing the mutagenicity of Crataegus preparations. It is assumed that the mutagenic activity demonstrated on Salmonella is based on the quercetin content, and the induction of SCE particularly on the presence of flavone-C-glycosides as well as of flavone aglycones. By comparison with the quantity of quercetin ingested with the food, however, the content of quercetin in the drug is so low that a risk for humans may be practically excluded.
No experimental data are available regarding carcinogenicity. The findings regarding gene toxicity and mutagenicity give no indication of carcinogenic risk of the drug in human use.
Clinical Data 1. Uses Decreasing cardiac output as described in functional Stage II of NYHA.
A physician must be consulted in cases where symptoms continue unchanged for longer than six weeks or in case of swelling of the legs. Medical diagnosis is absolutely necessary when pains occur in the region of the heart, spreading out to the arms, upper abdomen or the area around the neck, or in cases of respiratory distress (dyspnea).
Unless otherwise prescribed:
160 - 900 mg native, water-ethanol extract (ethanol 45 percent v/v or methanol 70 percent v/v, drug-extract ratio = 4 - 7:1, with defined flavonoid or procyanidin content), corresponding to 30 - 168.7 mg procyanidins, calculated as epicatechin, or 3.5 - 19.8 mg flavonoids, calculated as hyperoside in accordance with DAB 10, in two or three individual doses. Hawthorn fluidextract DAB 10:
Equivalent individual or daily dosage must be confirmed by clinical-pharmacological experiment or clinical study. Mode of Administration Liquid or dry pharmaceutical forms, for oral intake.
6 weeks minimum.
Note: The drug as well as aqueous, aqueous-ethanolic, and wine-based extracts and fresh juice from the plant are traditionally taken orally as a tonic and strengthener of the cardiac/circulatory functions. This information is based exclusively on tradition and long-term experience.
Ed. note: Stages I and II of NYHA refer to stages of heart disease in the New York Heart Association's 1994 Revisions to Classification of Functional Capacity and Objective Assessment of Patients with Diseases of the Heart: "Patients with cardiac disease but without resulting limitations of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain." Monopreparations of hawthorn flower, fruit, and leaf are discussed in the Unapproved Herbs section. A discussion of the reasons for approval of this hawthorn leaf with flower monograph and disapproval of other forms is found in the Introduction. -->