Hawthorn
Scientific Name(s): Crataegus oxyacantha L., C. laevigata (Poir.) DC, and C. monogyna Jacquin. Family: Rosaceae (roses)
Common Name(s): Hawthorn , English hawthorn , haw , maybush , whitethorn 1
Clinical Overview
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Uses of Hawthorn
Hawthorn has been used to regulate blood pressure and heart rhythm, to treat athersclerosis and angina pectoris, and as an antispasmodic and sedative.
Hawthorn Dosing
The usual recommended dose of hawthorn leaves and flowers is 4.5 to 6 g/day. Several standardized extracts ( Crataegutt , Faros 300 , Cardiplant ) are available that have been used in clinical trials at doses from 160 to 900 mg/day. The content of oligomeric proanthocyanidins or flavonoids is used for standardization of these extracts. 2 , 3 , 4 , 5 , 6
Contraindications
Avoid in people with an irregular heart rate or blood pressure.
Pregnancy/Lactation
Documented adverse effects. Avoid use. 7 Hawthorn causes uterine activity.
Hawthorn Interactions
No known interactions. A controlled study indicates that hawthorn does not interact with digoxin.
Hawthorn Adverse Reactions
No serious adverse reactions have been reported from hawthorn.
Toxicology
Hawthorn is reportedly toxic in high doses, which may induce hypotension and sedation.
Botany
Hawthorn is a spiny bush or small tree that grows up to 7.5 m in height. Its deciduous leaves are divided into three to five lobes. The white, strong-smelling flowers grow in large bunches and bloom from April to June. The spherical bright red fruit contains one nut ( C. monogyna ) or two to three nuts ( C. oxyacantha ). 1 Morphological and microscopical observation of certain Chinese hawthorn species has been performed. 8
History
The use of hawthorn dates back to Dioscorides, but the plant gained widespread popularity in European and American herbal medicine only toward the end of the 19th century. The flowers, leaves, and fruits have been used in the treatment of either high or low blood pressure, tachycardia, or arrhythmias. 9 The plant is purported to have antispasmodic and sedative effects. Hawthorn has been used in the treatment of atherosclerosis and angina pectoris. Preparations containing hawthorn remain popular in Europe 10 , 11 and have gained some acceptance in the US. 12
Chemistry
The leaves, flowers, bark, and fruits contain the flavonoid pigments hyperoside and vitexin-rhamnoside, leucoanthocyanidins, and the lactone crataeguslactone (a mixture of ursolic, oleanic, and crataegolic acids). 10 , 13 Flavonoid constituents from hawthorn have been frequently reported. 14 , 15 , 16 , 17 Glycoflavonoid structural characteristics have been evaluated. 18 Procyanidine and 2,3-cis-procyanidin have been isolated from hawthorn. 19 , 20 Chlorogenic acid from C. pyracantha Pers. has been found. 21 Analysis of active hawthorn components has been reviewed. 22
Hawthorn Uses and Pharmacology
Cardiovascular diseaseHawthorn's beneficial roles in cardiovascular disease have been extensively reviewed. 23 , 24 , 25 , 26 Pharmacokinetic, pharmacodynamic, and metabolic studies on hawthorn have been performed. 27 , 28 , 29
Because of its strong cardiac activity, hawthorn has been suggested to be of use in CHF 30 , 31 and cardiac performance. 32 The plant is known to contain cardiotonic amines. 33 The flavonoids cause an increase in coronary flow and heart rate and a positive inotropic effect.
Animal dataIn isolated animal hearts, the inhibition of the enzyme 3′,5′-cyclic adenosine menophosphate phosphodiesterase may be a mechanism by which hawthorn exerts its cardiac actions. 34 When tested in rat cardiac myocytes, hawthorn produced strong contraction of heart tissue, along with increases in energy turnover in certain processes. 35 Another study evaluated hawthorn in combination with digoxin to treat heart disease. 36 At least one report exists on the plant's potential antiarrhythmic effects. 37
Hawthorn flavonoid components also possess vasodilatory action. 34 , 38 Extracts of hawthorn dilate blood vessels, in particular coronary blood vessels, resulting in reduced peripheral resistance and increased coronary circulation. In vitro increases in coronary circulation ranging from 20% to 140% have been observed following the administration of a dose equal to ≈ 1 mg of the dry extract. 23
Hawthorn also exhibited vasorelaxant effects in isolated rat mesenteric arteries. 39 A double-blind study of the related species C. pinnatifida and its effect on 46 angina cases has been performed. 40
Hawthorn is also known to be beneficial in myocardial ischemia. 41 , 42 The flavonoid, monoacetyl-vitexinrhamnoside, possesses marked anti-ischemic properties in several in vitro models, suggesting improvement in myocardial perfusion. 43 Hawthorn's effects on oxygen-deprived rat heart cells have been reported. 44 The plant's influence on myocardial ischemia in dogs has also been evaluated. 45 , 46 Other studies of circulation have been done, including peripheral arterial circulation disorder 47 and varicose symptom complex. 48
Clinical dataResearch reveals little or no clinical data regarding the use of hawthorn for cardiac disease.
AtherosclerosisHawthorn has been studied in the prevention and treatment of atherosclerosis.
Animal dataA hawthorn preparation in combination was administered to animals, resulting in lower cholesterol, triglycerides, blood viscosity, and fibrinogen levels vs controls. 49 Another report finds tincture of hawthorn to increase bile acid excretion and decrease cholesterol synthesis in rats. The mechanism involves an up-regulation of hepatic LDL-receptors, resulting in a greater influx of cholesterol into the liver. Hawthorn was also found to enhance cholesterol degradation. 50 A drink containing hawthorn has lipid-lowering effects when studied in rats. 51
Clinical dataA drink containing hawthorn has lipid-lowering effects when studied in humans. 51
Other usesHawthorn has been studied for its effects on hypertension. 2 , 52 The plant has active components which cause vasorelaxation in rat mesenteric arteries. 39
Other effects of hawthorn include oxygen species scavenging activity, 53 anticomplementary activity, 54 and the ability to effectively treat elective mutism, a rare syndrome in which children with normal verbal capabilities refuse to speak for prolonged time periods. 55
Dosage
The usual recommended dose of hawthorn leaves and flowers is 4.5 to 6 g/day. Several standardized extracts ( Crataegutt , Faros 300 , Cardiplant ) are available that have been used in clinical trials at doses from 160 to 900 mg/day. The content of oligomeric proanthocyanidins or flavonoids is used for standardization of these extracts. 2 , 3 , 4 , 5 , 6
Pregnancy/Lactation
Documented adverse effects. Avoid use. 7 Hawthorn causes uterine activity.
Interactions
Preliminary data indicate there is no interaction between hawthorn and digoxin. The effects of hawthorn on the pharmacokinetics of digoxin were investigated in a randomized, crossover study of 8 healthy subjects. 56 Each subject received 0.25 mg of digoxin alone and with 450 mg hawthorn twice daily for 3 weeks. Compared with taking digoxin alone, hawthorn ingestion slightly decreased the area under the curve and peak plasma concentration of digoxin. However, the changes were not statistically significant.
Adverse Reactions
30 No serious adverse drug reactions have been reported from hawthorn, and it appears to be safe and effective for CHF. 30 However, higher doses have the potential to induce hypotension and sedation. The health professional and user must be aware of the potential of hawthorn to affect heart rate and blood pressure. 57
Hawthorn extract may increase the intracellular concentrations of cyclic AMP by influencing the activity of the enzyme phosphodiesterase, and it also may influence other mechanisms that activate adenylcyclase. 23 At least one report is available on hypersensitivity reaction to hawthorn, 58 and toxiderma as a result of the fruits of the plant. 59
Toxicology
The acute parenteral LD 50 of Crataegus preparations has been reported to be in the range of 18 to 34 mg/kg, with that of individual constituents ranging from 50 to 2600 mg/kg. 23 Acute oral toxicity has been reported to be in the range of 18.5 to 33.8 mg/kg. 60 In humans, low doses of hawthorn are usually devoid of adverse effects. 23
Hawthorn toxicity in general has been evaluated. 60
Bibliography
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35. Popping S, et al. Effect of a hawthorn extract on contraction and energy turnover of isolated rat cardiomyocytes. Arzneimittelforschung 1995;45(11):1157-61.
36. Wolkerstorfer H. Treatment of heart disease with a digoxin-crataegus combination. Munch Med Wochenschr 1966;108(8):438-41.
37. Thompson E, et al. Preliminary study of potential antiarrhythmic effects of Crataegus monogyna . J Pharm Sci 1974;63(12):1936-37.
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39. Chen Z, et al. Endothelium-dependent relaxation induced by hawthorn extract in rat mesenteric artery. Life Sci 1998;63(22):1983-91.
40. Weng W, et al. Therapeutic effect of Crataegus pinnatifida on 46 cases of angina pectoris—a double blind study. J Tradit Chin Med 1984;4(4):293-94.
41. Piotti L, et al. The therapeutic effect of hawthorn extract in myocardial hypoxia. Med Klin 1965;60(53):2142-45.
42. Massoni G. On the use of hawthorn extract ( Crataegus ) in the treatment of certain ischemic myocardial diseases in old age. G Gerontol 1968;16(9):979-84.
43. Schussler M, et al. Functional and antiischaemic effects of Monoacetyl-vitexinrhamnoside in different in vitro models. Gen Pharmacol 1995;26(7):1565-70.
44. Li L, et al. Studies on hawthorn and its active principle. II. Effects on cultured rat heart cells deprived of oxygen and glucose. J Trad Chin Med 1984;4(4):289-92.
45. Li L, et al. Studies on hawthorn and its active principle. I. Effect on myocardial ischemia and hemodynamics in dogs. J Trad Chin Med 1984;4(4):283-88.
46. Lievre M, et al. Cardiovascular effects of hyperoside extracted from hawthorn in anesthetized dogs. Ann Pharm Fr 1985;43(5):471-77.
47. Di Renzi L, et al. On the use of injectable crataegus extracts in therapy of disorders of peripheral arterial circulation in subjects with obliterating arteriopathy of the lower extremities. Boll Soc Ital Cardiol 1969;14(4):577-85.
48. Gehrels P. Therapy of varicose symptom complex with Rexiluven. Ther Ggw 1970;109(8):1163-66.
49. He G. Effect of the prevention and treatment of atherosclerosis of a mixture of Hawthorn and Motherwort. Chung Hsi i Chieh Ho Tsa Chih 1990;10(6):361, 326.
50. Rajendran S, et al. Effect of tincture of Crataegus on the LDL-receptor activity of hepatic plasma membrane of rats fed an atherogenic diet. Atherosclerosis 1996;123(1-2):235-41.
51. Chen J, et al. Hawthorn (shan zha) drink and its lowering effect on blood lipid levels in humans and rats. World Rev Nutr Diet 1995;77:147-54.
52. Rigo J, et al. The effect of magnesium-enriched hawthorn syrup (Viroma) on experimental hypertension. Orv Hetil 1968;109(37):2059-60.
53. Bahorun T, et al. Oxygen species scavenging activity of phenolic extracts from hawthorn fresh plant organs and pharmaceutical preparations. Arzneimittelforschung 1996;46(11):1086-89.
54. Shahat T, et al. Anti-complementary activity of Crataegus sinaica . Planta Medica 1996;62(1):10-13.
55. Krohn D, et al. A study of the effectiveness of a specific treatment for elective mutism. J Amer Acad Child Adolesc Psychiatry 1992;31(4):711-18.
56. Tankanow R, et al. Interaction study between digoxin and a preparation of Hawthorn ( Crataegus oxyacantha ). J Clin Pharmacol . 2003;43:637-642.
57. Miller L. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998;158(20):2200-11.
58. Steinman H, et al. Immediate-type hypersensitivity to Crataegus monogyna . Contact Dermatitis 1984;11(5):321.
59. Rogov V. Toxiderma due to the fruits of the hawthorn. Vestn Dermatol Venerol 1984;7:46-47.
60. Ammon H, et al. Crataegus toxicology and pharmacology. Planta Med 1981;43:105.
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