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Hawthorn (Craetegus species, fam Rosacea) has been utilized in European herbal medicine for centuries to promote healthy heart and circulatory system, help improve heart conditions, such as hearth failure, hypertension, angina pectoralis, tachycardia, arrhythmia (1). It is believed to be generally safe, well tolerated over long term treatment and especially recommended to help reduce age related changes (atrophy, muscular degeneration and coronary arteriosclerosis) in heart muscle. Both leaves/flowers (as teas, tinctures, extracts) and berries (as tinctures and extracts) have been used. Usually the tea is made of 1 - 2 teaspoons of flower/leaf mixture and taken 2 - 3 times a day. Typical suggested dose for standardized extracts ( approx. 2% of vitexin-rhamnozide and/or 18% of total proanthocyanidins) is in the range of 250 - 600 mg daily.
Known active ingredients of Hawthorn are represented by three groups of compounds: 1) proanthocyanidins (oligomeric procyanidins) such as procyanidin B-5, proanthocyanidin A-2, procyanidin B-2, procyanidin C-1; 2) flavonoids and 3) catechins (epicatechin). Most aboundant flavonoids of Hawthorn are quercetin, hyperoside (quercetin 3-O-galactoside), rutin (quercetin 3-O-rutinoside), vitexin, luteolin, crataemon, monoacetyl-vitexinrhamnoside, rhamnosylvitexin, monoacetylrhamnosylvitexin (2,3).
Growing body of scientific evidences confirm traditional claims of heart beneficial action of Hawthorn. In animal studies extract of Hawthorn show hypotensive and a antiarrhythmic action on ischaemic myocardium(4). Extracts were demonstrated to have anti-arrhythmic properties and increase heart muscle revascularization following experimental myocardial infarction (5). Hawthorn flavonoids were shown to cause an increase of coronary flow and increase of the relaxation velocity (most potent luteolin-7-glucoside, hyperoside and rutin) in the model of isolated guinea pig heart (7). Extracts from fruits and leaves of Hawthorn as well as a number of individual proanthocyanidins (procyanidin B-5 , proanthocyanidin A-2, procyanidin B-2, and procyanidin C-1) and to a smaller degree flavonoids (rutin, vitexin, quercetin , rhamnosylvitexin ) are able to inhibit complement-mediated hemolysis (8) and inhibit platelet adhesion by decreasing thromboxane A2 biosynthesis (9). Monoacetyl-vitexinrhamnoside, a Hawthorn flavonoid with phosphodiesterase-inhibitory properties shows antiischemic properties in ex vivo models. These observations suggest that Hawthorn may improve myocardial blood flow parameters (10). In vitro studies demonstrate the ability of Hawthorn to affect membrane ion channels and induce intracellular accumulation of cAMP in cardiac smooth muscle cells (11). Hawthorn procyanidins may be responsible for the nitric oxide-mediated relaxation in isolated rat aorta, possibly via activation of tetraethylammonium-sensitive K+ channels (6). These and other effect may account for the decreased ventricular arrhythmias, the positive ionotropic effect and the decrease in diastolic blood pressure seen in the in vivo Hawthorn studies (11). Overall laboratory studies indicate that Hawthorn is able to improve myocardial circulation and parameters of cardiac muscle activity.
Several clinical trials have shown beneficial action of Hawthorn on objective signs and subjective symptoms of congestive heart failure (12,13). No adverse drug reactions have been reported. In one of the most representative trials efficacy and tolerance of the Hawthorn extract were monitored in a multicenter study on 1011 patients with cardiac insufficiency stage NYHA II (13). Almost 2/3 of the patients felt better or much better following the 24 weeks treatment. More than 3/4 of the participating physicians noted a good or a very good efficacy, and 98.7% noted a good or a very good tolerance. Authors conclude that high-dose Hawthorn therapy is an efficient, well-tolerated and easily regulated therapeutic alternative for patients suffering from cardiac insufficiency stage.
1. Fugh-Berman A. Herbs and dietary supplements in the prevention and treatment of cardiovascular disease. Prev Cardiol 2000; 3(1): 24
2. Petkov V. Plants and hypotensive, antiatheromatous and coronarodilatating action. Am J Chin Med 1979; 7(3): 197
3. Bahorun T, Gressier B, Trotin F, Brunet C, Dine T, Luyckx M, Vasseur J, Cazin M, Cazin JC, Pinkas M. Oxygen species scavenging activity of phenolic extracts from hawthorn fresh plant organs and pharmaceutical preparations. Arzneimittelforschung 1996; 46(11): 1086
4. Garjani A, Nazemiyeh H, Maleki N, Valizadeh H. Effects of extracts from flowering tops of Crataegus meyeri A. Pojark. on ischaemic arrhythmias in anaesthetized rats. Phytother Res 2000; 14(6): 428
5. Guendjev Z. Experimental myocardial infarction of the rat and stimulation of the revascularization by the flavonoid drug crataemon. Arzneim.-Forsch./Drug Res 1977; 27 (II): 1576
6. Kim SH, Kang KW, Kim KW, Kim ND. Procyanidins in crataegus extract evoke endothelium-dependent vasorelaxation in rat aorta. Life Sci 2000; 67(2): 121
7. Schussler M, Holzl J, Fricke U. Myocardial effects of flavonoids from Crataegus species. Arzneimittelforschung 1995; 45(8): 842
8. Shahat AA, Hammouda F, Ismail SI, Azzam SA, De Bruyne T, Lasure A, Van Poel B, Pieters L, Vlietinck Anti-complementary activity of Crataegus sinaica. AJ. Planta Med 1996; 62(1): 10
9. Vibes J, Lasserre B, Gleye J, Declume C. Inhibition of thromboxane A2 biosynthesis in vitro by the main components of Crataegus oxyacantha (Hawthorn) flower heads. Prostaglandins Leukotrienes Essential Fatty Acids 1994; 50: 173
10. Schussler M, Holzl J, Rump AF, Fricke U. Functional and antiischaemic effects of Monoacetyl-vitexinrhamnoside in different in vitro models. Gen Pharmacol 1995; 26(7): 1565
11. Siegel G, Casper U, Schnalke F, Hetzer R. Hawthorn effect on canine papillary muscle action potential Phytotherapy Res 1996; 10: S195
12. Weihmayr T, Ernst E. Therapeutic effectiveness of Crataegus Fortschr Med 1996; 114(1-2): 27
13. Tauchert M, Gildor A, Lipinski J. High-dose Crataegus extract WS 1442 in the treatment of NYHA stage II heart failure Herz 1999; 24(6): 465
Tauchert M, Gildor A, Lipinski J.
High-dose Crataegus extract in the treatment of NYHA stage II heart failure
Herz 1999; 24(6): 465-74
The efficacy and tolerance of the standardized hawthorn (crataegus) extract were tested in a multicenter utilization observational study. We monitored 1,011 patients with cardiac insufficiency stage NYHA II, treated with this extract (Crataegutt novo 450, 1 tablet b.i.d.) over a period of 24 weeks. During and at the end of the observation period a significant improvement in clinical symptoms (reduced performance in the exercise tolerance test, fatigue, palpitation and exercise dyspnea) was observed. Ankle edema and nocturia disappeared by 83%, and by half of the patients respectively manifesting these symptoms before treatment. The improvement and economization of cardiac performance were additionally shown by a reduction in blood pressure, an increased maximal exercise tolerance and a reduction in the difference in the pressure/heart rate product (PHRP). The positive effects of extract were further demonstrated by an improved ejection fraction and an increased percentile shortening fraction measured using M-mode echocardiography. The stabilizing effect of the hawthorn extract on the heart rate was shown by a slower rest pulse, as well as by an increase in the number of day and night normorhythmic patients, as documented by long-term ECG. The reduction in the number of patients showing ST depressions, arrhythmias and ventricular extrasystoles at the maximum exercise level is regarded as an indication for an improved myocardial perfusion. Fourteen side effects were noted. In two cases (abdominal discomfort and facial pains accompanied by tachycardia) a possible relationship with the hawthorn therapy, was postulated which however was considered unlikely by the treating physicians. Almost 2/3 of the patients felt better or much better following the 24 weeks of treatment. More than 3/4 of the participating physicians noted a good or a very good efficacy, and 98.7% noted a good or a very good tolerance. High-dose hawthorn therapy is an efficient, well-tolerated and easily regulated therapeutic alternative for patients suffering from cardiac insufficiency stage
Hertog MGL, Feskens EJM, Hollman PCH, Katan MB, Kromhout D.
Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study.
Lancet 1993; 342: 1007-1011
The study analysed the diet of 805 men in The Netherlands between the ages of 65 and 84 years for the intake of flavonoid. The three main sources for flavonoids in their diet were black tea, onions, and apples. The men were followed for a 5-year period, and the flavonoid content of their diet was inversely associated with mortality from coronary heart disease. Although this study did not look at hawthorn in particular, an association appears to exist between flavonoid consumption and coronary heart disease mortality. The finding of this long-term study are in agreement with the short-term clinical studies of hawthorn.
Von Eiff M, Brunner H, Haegeli A, Kreuter U, Martina B, Meier B, Schaffner W.
Hawthorn/passion flower extract and improvement in physical exercise capacity of patients with dyspnoea class II the NYHA function classification.
Acta Therapeutica 1994; 20: 47-66.
The authors used a randomized, double-blind, placebo-controlled, parallel study to analyse the effect of a hawthorn/passion flower extract or placebo on physical performance. A total of 40 patients between the ages of 53 and 86 years were evaluated; all had dyspnoea with New York Heart Association class II
function. Exercise capacity was evaluated by 6-minute walking and bicycle ergometer tests. Blood lactate levels, heart rate and blood pressure were measured during exercise, as well as symptoms and urine biochemical parameters. Patients receiving the hawthorn/passion flower extract had an increase in walking capacity. Both the hawthorn/passion flower group and the placebo group had an increase in the bicycle ergometer test of about 10% above baseline. The group receiving the extract had a slight but significant decrease in resting heart rate, mean diastolic pressure during exercise and total serum cholesterol.
The focus of this study was the effect of the hawthorn/passion flower extract on exercise capacity; but the effect on diastolic blood pressure, heart rate and cholesterol are also significant and merit further clinical investigation. The patients were mainly women (37 versus 3 men). Additional studies are required to
examine the effects in both genders. Two ml of extracts was administered three times a day to the patients. As pointed out by the author, a similar study by Schmidt et al.1 used higher doses of hawthorn for 8 weeks and found a significant effect of hawthorn on bicycle ergometer tests compared with control. Von Eiff points out that it is difficult to compare different hawthorn preparations, since there is no standard method of extraction.
Weihmayr T, Ernst E.
Therapeutic effectiveness of Crataegus
Fortschr Med 1996 114(1-2):27-9
Hawthorn (crataegus) has been used since antiquity for medicinal purposes. More recent research suggests it to be useful in congestive heart failure. Rigorous clinical trials show benefit concerning objective signs and subjective symptoms of congestive heart failure stage NYHA-II. No adverse drug reactions have been reported. It is therefore concluded that crataegus is an effective and safe therapeutic alternative for this indication.
Chen JD, Wu YZ, Tao ZL, Chen ZM, Liu XP
Hawthorn (Shan Zha) drink and its lowering effect on blood lipids levels in humans and rats.
World Rev Nutr Diet 1995; 77: 147-154.
Hawthorn's ability to reduce body weight, body fat and blood lipids was studied on rats and humans. In the human portion of the study, 30 volunteers diagnosed as hyperlipidaemic participated. After consuming hawthorn for 1 month, average cholesterol levels decreased from 7.31 ± 1.04 mmol/l to 6.19 ± 1.56 mmol/l (P < 0.001). Serum triglyceride levels decreased from 1.93 ± 0.92 to 1.75 ± 0.96 mmol/l. Hawthorn did not raise HDL levels in the human study. Hawthorn was also shown to decrease
serum levels of lipid peroxidate malonic dialdehyde levels from 3.2 ± 0.9 to 2.5 ± 0.4 nmol/ml, suggesting a strong antioxidative effect.
This paper concluded that 1 month of hawthorn ingestion significantly decreased serum cholesterol, LDL-C and triglycerides, and a significant MDA reduction showed an antioxidative effect. _______________________________________________________________________________________________
The animal experiments were performed on 37 Sprague-Dawley male rats divided into three groups; one was given a hawthorn drink containing 4-6% sugar, another water containing 8% sugar and the third group received tap water. Body weights of the rats were lower in hawthorn-fed rats, but the decrease in body weight was not statistically significant (perhaps due to the small number of rats used). The hawthorn group did have significantly decreased body fat, total cholesterol levels and triglyceride level compared with the two control groups. The HDL level was greater in the hawthorn group than in those drinking sugar water, but was less than in the group drinking tap water. The rats drinking sugar water significantly decreased their solid food intake compared with the tap-water-fed rats. In the hawthorn-fed rats, food intake fell
to a level between the two control groups.
Both rat and human data showed a decrease in total cholesterol, LDL cholesterol and triglycerides when hawthorn was ingested. Unfortunately, the number of humans used for this study was small, 25 women and 5 men, and the study was neither double-blind nor placebo controlled. It was noted that the patients placed on hawthorn stopped taking other medications, but the medications they stopped were not described. The patients kept their daily life, activity and diet constant, but analyses of these variables were not given. Although, this was not a double-blind placebo-controlled study, the effects on cholesterol are
in agreement with the previously cited study.
In the animal study, the rats were given either a hawthorn drink containing 4-6% sugar, water with 8% sugar or tap water. The results showed a difference between the group consuming 8% sugar water and the group consuming tap water. The group consuming hawthorn fell between these two groups in some of the analysed
parameters, making it difficult to establish whether some of the differences were due to the composition of the animals' diet. Perhaps an isocaloric group to compare with the hawthorn animals would have been helpful in determining its specific effects.
Bahorun T, Gressier B, Trotin F, Brunet C, Dine T, Luyckx M, Vasseur J, Cazin M, Cazin JC, Pinkas M.
Oxygen species scavenging activity of phenolic extracts from hawthorn fresh plant organs and pharmaceutical preparations
Arzneimittelforschung 1996 Nov;46(11):1086-9
Different extracts of hawthorn from fresh and dried flowers and pharmaceutical preparations were analysed for their antioxidant activity in vitro. These preparations were also analysed for their content of total phenols, total proanthocyanidin and total flavonoid. Antioxidant activity was determined by measuring scavenging ability of hydrogen peroxide, superoxide anion and hypochlorous acid. This study concluded that fresh young leaves, fresh floral buds and pharmaceutical preparations of dried flowers all exhibited in vitro antioxidant activities using all three models to measure antioxidant activity in vitro. The activity appeared to be bound to the total phenolic proanthocyanidin and flavonoid contents. The concentrations needed for the pharmaceutical preparations were slightly higher than those in the fresh preparation. This study demonstrates in vitro antioxidant actions of hawthorn preparations. The role of free radicals in disease, including atherosclerosis, was reviewed by Trilling and Jaber.2 The antioxidant effects of hawthorn theoretically may be cardioprotective by having anti-atherosclerotic actions, as well as decreasing reperfusion damage to an ischaemic myocardium. In addition to the effect of hawthorn on ion channel activity, antioxidant actions may be an additional component to it clinical effect.
Chen HB, Jiang JL, Yu L, Gao GY.
Comparisons of pharmacological effect and LD50 among four kinds of Hawthorn fruit
Zhongguo Zhong Yao Za Zhi 1994 Aug;19(8):454-5, 510
Four kinds of Hawthorn Fruit, namely Large Chinese Hawthorn, Chinese Hawthorn, Nippon Hawthorn and Yunnan Hawthorn, were compared in animal experiments. Their effects on small intestine motion, myocardial ischemia and hypercholesterolemia have been found different from each other.
Garjani A, Nazemiyeh H, Maleki N, Valizadeh H.
Effects of extracts from flowering tops of Crataegus meyeri A. Pojark. on ischaemic arrhythmias in anaesthetized rats
Phytother Res 2000 Sep;14(6):428-31
Different species of Crataegus, commonly called Hawthorn, were reported to possess wide pharmacological effects on the cardiovascular system. In the present study, chloroform, ethylacetate and methanol (70%) extracts of the flowering tops of Crataegus meyeri A. Pojark. were studied. The extracts were tested on the incidence and severity of arrhythmias induced by a period of myocardial ischaemia in open-chest anaesthetized male Wistar rats. Infusion of a hydroalcohol extract (1 mg/kg/min) resulted in a significant decrease in the total number of ventricular ectopic beats (from 1494 +/- 362 in the control to 634 +/- 102), mainly by reduction of beats occurring as ventricular tachycardia. A chloroform extract (1 mg/kg/min) also reduced the total number of ventricular ectopic beats but this reduction was due to the decrease of single extrasystoles. A significant reduction in the time spent for ventricular fibrillation was seen by the hydroalcohol and ethylacetate extracts. There were no significant changes in the heart rate and blood pressure during the extract infusion. However, bolus injection of all the extracts caused a significant reduction in the blood pressure. Thus, the extracts of Crataegus meyeri have a hypotensive and a potential antiarrhythmic action on ischaemic myocardium and may possess active principles.
Experimental myocardial infarction of the rat and stimulation of the revascularization by the flavonoid drug crataemon.
Arzneim.-Forsch./Drug Res 1977; 27 (II): 1576-1579.
The left coronary artery of 67 female Wistar rats was ligated. Two days before and 10 days after the ligation, 34 of the experimental rats were treated with 150 mg/kg crataemon, a purified flavonoid extracted from Crataegus monogyna leaves. The other 33 rats were not treated. Twenty-seven of the control and 32
of the experimental rats survived the procedure and were sacrificed 10 days post-ligation. Histological sections demonstrated that the necrotic focus was smaller in the experimental rats than in the controls. It was also noted that there were significantly more capillaries, venules and arterioles in the experimental rats compared with controls. The ratio of venous vessels to arterial vessels was similar in both experimental and control animals. Deaths of animals within 2-5 days post-surgery were attributed to bronchopneumonia. The
author suggests that decreased post-operative mortality in the experimental animals might be due to the capillary strengthening effect of crataemon. The high level of revascularization produced by crataemon causes an immediate high blood flow, containing many phagocytic cells, to the necrotic tissue, thus
decreasing the dimension of the necrotic focus. One specific compound found in hawthorn, namely the flavonoid crataemon, was analysed for its effect on reperfusion of the myocardium after ligation of a coronary vessel. In both this study and the previous one, the mortality was decreased in the treated group compared with the control group. Synergistic actions of this compound with other compounds found in extractions of hawthorn may exist. While it is important to study the effect of an individual component, comparison to the whole herbal extract is also useful. Consumption of hawthorn over a longer duration of time may have additional effects that are not noted in acute administration.
If hawthorn increases vascularization of the myocardium, perhaps collateral vessels develop over the long term and have a protective effect. Hawthorn may possess anti-arrhythmic properties and increase revascularization.
Effect of the prevention and treatment of atherosclerosis of a mixture of Hawthorn and Motherworn
Zhong Xi Yi Jie He Za Zhi 1990 10(6): 361
Two groups of cocks were divided into controls and medications. High lipid food was given to both groups. The medications were given mixture of Hawthorn and Motherworn. The effect on prevention and treatment of atherosclerosis with the mixture was observed. The results showed that cholesterol, beta-lipid protein, triglyceride, blood sugar, whole blood viscosity, plasma viscosity, electrophoresis of red cell and fibrinogen in the medications were statistically lower than that in the controls. The results confirms the effect of the mixture on the prevention and treatment of atherosclerosis in the pathology section of coronary artery.
Kim SH, Kang KW, Kim KW, Kim ND.
Procyanidins in crataegus extract evoke endothelium-dependent vasorelaxation in rat aorta
Life Sci 2000;67(2):121-31
The extract of Crataegus, a mixture of flavonoids and procyanidins extracted from hawthorn, Crataegus oxyacantha, L. and C. monogyna Jacq., relaxed vascular tone or increased production of cyclic GMP in the rat aorta, but flavonoid components of Crataegus extract, hyperoside, rutin and vitexin, did not affect the vascular tone. The aim of the present study was to characterize the endothelium-dependent relaxation elicited by procyanidins fractionated from Crataegus extract in isolated rat aorta. Procyanidins caused endothelium-dependent relaxation which was associated with the production of cyclic GMP. Both responses to these procyanidins were inhibited by methylene blue or N(G)-nitro-L-arginine, but not by indomethacin. Relaxation in response to procyanidins was not affected by atropine, diphenhydramine, [D-Pro2,D-Trp7,9]substance P, propranolol, nifedipine, verapamil and glibenclamide, but were markedly reduced by tetraethylammonium. These findings showed that procyanidins in Crataegus extract may be responsible for the endothelium-dependent nitric oxide-mediated relaxation in isolated rat aorta, possibly via activation of tetraethylammonium-sensitive K+ channels.
Ischaemia- and reperfusion-induced cardiac injury: effects of two flavonoid containing plant extracts possessing radical scavenging properties.
Naunyn-Schmiebergís Arch Pharmacol 1992; 345
In this abstract, hawthorn, Ginkgo biloba or vehicle (controls) were administered 5 minutes prior to transient occlusion of a coronary artery. Reperfusion-induced ventricular fibrillations were observed in 88% of control animals (n = 25), and in only 20% of two groups of hawthorn-treated animals, one treated with 0.5 mg/kg, the other with 5 mg/kg. The mean duration of the arrhythmia was also decreased. Hawthorn, however, did not effect the reperfusion-induced CPK release. Ginkgo biloba was noted to have an effect on reperfusion-induced ventricular arrhythmia but only with the higher dose of 3-5 mg/kg; however, the duration of the arrhythmia was not effected. Ginkgo biloba was effective in decreasing the ischaemia reperfusion-induced rise in CPK verses controls: 5.7 ± 0.4 U/g versus 13.1 ± 1.15 U/g, respectively.
While data from this study are interesting, the study was published as an abstract, not as a full journal article. Not all data are presented. Histological analysis of the myocardium may have contributed additional information about the extent of necrosis which CPK alone cannot address. Analysis of the extracts of hawthorn and Ginko biloba were not presented. The results may have important consequences, particularly the decrease in mortality from ventricular arrhythmias.
Rajendran S, Deepalakshmi PD, Parasakthy K, Devarj H, Niranjali Devaraj S.
Effect of tincture of Crataegus on the LDL-receptor activity of hepatic plasma membrane of rats fed an atherogenic diet.
Atherosclerosis 1996; 123: 235-241.
Extract of hawthorn has been shown to lower total and LDL cholesterol. The authors propose the hypothesis that the decrease may be due to an increase in LDL-receptor activity of hepatic membranes. When hawthorn was administered to rats fed an atherogenic diet, there was a significant increase of binding of LDL
to liver plasma membrane in vitro. The liver membrane bound an increased number LDL molecules compared with controls. Hawthorn extract was also shown to increase bile acid excretion and to depress hepatic cholesterol synthesis in these rats.
The hawthorn extract used in this study was an alcohol extract. An equivalent quantity of ethanol was not given to the control groups. This may or may not be an issue depending on the quantity of ethanol which the hawthorn experimental group consumed. Although this point was not addressed by the authors and may
effect the results, the mechanism suggested may have a physiological effect in humans.
Schussler M, Holzl J, Fricke U.
Myocardial effects of flavonoids from Crataegus species.
Arzneim.-Forsch./Drug Res 1995; 45 (II).
Different compounds in hawthorn were tested for their effects on coronary flow, heart rate and ventricular systolic and diastolic pressure in Langendorff perfused isolated guinea pig hearts at a constant pressure of 70 cm H2O. An increase in coronary blood flow was caused by luteolin-7-glucoside (186%), hyperoside (66%) and rutin (66%). There was an increase in relaxation velocity by luteolin-7-glucoside (104%), hyperoside (62%) and rutin (73%). The major effects of these compounds were at 0.5 mmol/l. These compounds also had small positive inotropic and chronotropic effects. Vitexin, vitexin-rhamnoside and monoacetyl-vitexin-rhamoside had similar actions, but to a lesser extent. Adrenergic activity of the compounds was abolished by addition of propanolol or reserpine.
This study analyses some of the individual components of hawthorn extracts. As expected, more than one compound accounts for the actions of hawthorn. This work is essential for optimizing the preparations of hawthorn. In addition to the actions of individual components, the interaction of the components is crucial
to the understanding of this herb. The effects may be additive, or it may be that only one of the components maximizes the desired effect. Molecular physiological effector mechanisms of hawthorn extract in cardiac papillary muscle and coronary vascular smooth muscle.
Shahat AA, Hammouda F, Ismail SI, Azzam SA, De Bruyne T, Lasure A, Van Poel B, Pieters L, Vlietinck
Anti-complementary activity of Crataegus sinaica.
AJ. Planta Med 1996 Feb;62(1):10-3
The 80% and 70% acetone extracts from fruits and leaves of Crataegus sinaica Boiss (Rosaceae) and the ethyl acetate-, butanol-, and water-fractions obtained from these initial extracts as well as the isolated compounds, quercetin (1) (1), hyperoside (quercetin 3-O-galactoside) (2) (2), rutin (quercetin 3-O-rutinoside) (3) (2), vitexin (4) (1), rhamnosylvitexin (5) (3), monoacetylrhamnosylvitexin (6) (3), epicatechin (7) (4), procyanidin B-5 (8) (4), proanthocyanidin A-2 (9) (5), procyanidin B-2 (10) (4), and procyanidin C-1 (11) (4), were tested for their influence on the classical (CP) and alternative (AP) pathways of complement-mediated hemolysis. All extracts and fractions showed a strong anti-complementary effect in a dose-dependent way which was more pronounced on the CP than on the AP. The results indicated that the pure proanthocyanidins were active on the CP. Procyanidin C-1 and proanthocyanidin A-2 were the most active on the CP and also showed activity on AP, whereas the flavonoids isolated were generally less active. However, rutin, showed a strong activity, quercetin and rhamnosylvitexin a moderate activity on the CP. This is the first report on the chemical constituents and complement-modulating activity of C. sinaica and on the occurrence of proanthocyanidin A-2 (9) in hawthorn.
Schussler M, Holzl J, Rump AF, Fricke U.
Functional and antiischaemic effects of Monoacetyl-vitexinrhamnoside in different in vitro models.
Gen Pharmacol 1995 26(7):1565-70
Functional and antiischaemic effects of monoacetyl-vitexinrhamnoside (AVR), a flavonoid with phosphodiesterase (PDE)-inhibitory properties contained in Crataegus species (Hawthorn, Rosaceae) were studied in several in-vitro models. 2. In rabbit isolated femoral artery rings, AVR concentration-dependently reduced developed tension. Vasodilation by AVR was reduced after inhibiting EDRF formation by L-NG-nitro arginine. 3. In spontaneously-beating Langendorff-guinea pig hearts, AVR concentration-dependently enhanced heart-rate, contractility, lusitropy and coronary flow. 4. In isolated electrically-driven Langendorff-rabbit hearts, acute regional ischemia (MI) was induced by coronary artery occlusion and quantified from epicardial NADH-fluorescence photography. AVR (5 x 10(-5) mol/l) induced a slight numerical increase of left ventricular pressure and coronary flow (p > 0.05). MI was reduced (p < 0.05). 5. Monoacetyl-vitexinrhamnoside is an inodilator whose vasodilatory action may be mediated in part by EDRF in addition to PDE-inhibition. Monoacetyl-vitexinrhamnoside does possess marked antiischemic properties even in isolated hearts, suggesting an improvement of myocardial perfusion.
Schussler M, Holzl J, Fricke U.
Myocardial effects of flavonoids from Crataegus species.
Arzneimittelforschung 1995 Aug;45(8):842-5
The influence of the main flavonoids from Crataegus species (hawthorn, Rosaceae) on coronary flow, heart rate and left ventricular pressure as well as on the velocity of contraction and relaxation was investigated in Langendorff perfused isolated guinea pig hearts at a constant pressure of 70 cmH2O. Drug action was evaluated in a concentration range of 10(-7) to 5 x 10(-4) mol/l. An increase of coronary flow caused by the O-glycosides luteolin-7-glucoside (186%), hyperoside (66%) and rutin (66%) as well as an increase of the relaxation velocity (positive lusitropism) by luteolin-7-glucoside (104%), hyperoside (62%) and rutin (73%) were the major effects observed at a maximum concentration of 0.5 mmol/l. Furthermore, slight positive inotropic effects and a rise in heart rate were seen. Similar but less intensive actions were found with the C-glycosides vitexin, vitexin-rhamnoside and monoacetyl-vitexin-rhamnoside. Possible beta-adrenergic activities of the flavonoids could be excluded by the addition of propranolol in fixed concentrations of 10(-8) to 10(-5) mol/l. Moreover, pretreatment of the animals with reserpine (7 mg/kg) did not influence myocardial activity of hyperoside (10(-4) mol/l). As previous experiments showed an inhibition of the 3',5'-cyclic adenosine monophosphate phosphodiesterase, the results suggest an inhibition of this enzyme as the possible underlying mechanism of cardiac action of flavonoids from Crataegus species
Siegel G, Casper U, Schnalke F, Hetzer R.
Hawthorn effect on canine papillary muscle action potential
Phytotherapy Res 1996; 10: S195-S198.
Hawthorn extracts (with flavonoid concentrations of 10-7 to 10-5 mol/l) influence canine papillary muscle action potential. The authors noted an increase in the maximal upstroke velocity and overshoot of the action potential, indicating an enhancement of the inward fast Ca2+ current. This action is similar to beta-adrenergic stimulation. The enhancement of the Ca2+ channel in this case is caused by stimulation of adenylate cyclase, which in turn activates protein kinase A, which in turn phosphorylates Ca-activatable K+ channels. This chain of events causes an increase in the open state probability of the channel. The effects of hawthorn differ from the beta-adrenergic stimulation in that there is also slowing of the final repolarization phase. Other ion channels must therefore be affected by hawthorn which are not affected by pure adrenergic
The effect of hawthorn on human coronary arteries smooth muscle action potential was studied in vitro. Coronary arteries were obtained from heart transplant patients suffering from dilated cardiomyopathy or extensive atherosclerosis. Both normal and atherosclerotic vessels were studied. Hawthorn extract caused an
increase in the K+ conduction and a hyperpolarization of the membrane potential. This hyperpolarization increases the L-type Ca2+ channel in the closed position. The Ca2+ inward current into vascular smooth muscle was decreased by 16.3%, causing a decrease in wall tension and dilation of the vessels.
Previous studies have shown that hawthorn increases intracellular cAMP, which in turn, activates protein kinase A. This study, in addition to the previously referenced study by Schussler et al., demonstrates that the actions of hawthorn cannot be explained purely by adrenergic properties. Hawthorn may activate
protein kinase A, but it also affects targets not phosphorylated by PK-A or other PK-A agonists. These in vitro data, demonstrating the ability of hawthorn to affect ion channels in the membrane of cardiac and smooth muscle cells may account for the decreased ventricular arrhythmias, the positive inotropic effect
and the decrease in diastolic blood pressure seen in the in vivo studies referenced earlier.
Vibes J, Lasserre B, Gleye J, Declume C.
Inhibition of thromboxane A2 biosynthesis in vitro by the main components of Crataegus oxyacantha (Hawthorn) flower heads.
Prostaglandins Leukotrienes Essential Fatty Acids 1994; 50: 173-175.
The authors had previously demonstrated that hawthorn extracts inhibited thromboxane A2 in vitro. This study analysed specific components of hawthorn flower heads for their ability to inhibit thromboxane A2.
Vitexin-2"-o-rhamnoside, which is flavonoid (yellow pigmented), had an inhibitory effect on thromboxane A2 biosynthesis; vitexin was even more potent, but it is not a regular component of hawthorn; instead it forms over time. Catechin and epicatechin, which are flavans (uncoloured), are known to be present in hawthorn, but were not isolated by the authors' method of extraction. These compounds were tested and found to significantly inhibit thromboxane A2 biosynthesis.
The significance of inhibition of platelet adhesion in ischaemic heart disease has been well studied. This in vitro study demonstrates that components of hawthorn may inhibit platelet adhesion by decreasing thromboxane A2 biosynthesis.
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Traditional Hawthorn remedies
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