PLANT DESCRIPTION
Crataegus Monogyna, commonly known as hawthorn, is a bush with thorns and it is member of the family of Rosaceae. The flowers are grouped in corymbs, its petals are white-pink and in November or December we can see its red oval fruits. It is found in the woods, especially in Europe, North Africa, West Asia and North America. The drug from flowers has anti-spasmodic, hypotensive, cardiotonic, diuretic and nervine-sedative properties. Hawthorn is most valuable remedy for cardiovascular system and considered to be one of the best cardiac tonic found in plant kingdom. It dilates peripheral blood vessels, increases metabolism in the heart muscle, dilates coronary vessels and improves blood supply to the heart and thereby help in treating heart disease and mitigating symptoms in early stage of heart failure.
MAIN CONSTITUENTS
These compounds are:
• Flavonoids such as vitexin, quercetin, apigenin, hiperoside etc;
• Oligomeric proanthocyanidins (OPC);
• Triterpenic acids such as crategolic acid, caffeic acid, ursolic acid, oleanolic acid ect;
• Amines, sterols, glycosides ect;
• Vitamins like B1, B2, C, E, ascorbate and carotene.
CLASSIFICATION
Kingdom: Plantae
Class: Magnoliopsida
Order: Rosales
Family: Rosaceae
Genus: Crataegus
Speciem: C.Monogyna
Common name: Hawthorn
MOLECULAR MECHANISM
The flavonoids and procyanidins play a protective role by promoting the expansion of the coronary, and the vascularization of the myocardium, acting on the enzyme c-AMP-phosphodiesterase. However, it has been documented inhibitory actions of the angiotensin-converting enzyme (ACE) and inhibitory action on potassium channels: lengthening the refractory time and the duration of action potential. The OPC are antioxidants and inhibitors of elastase HNE (Human Neutrophil Elastase) and malondialdehyde (MDA). There is also an effect of protecting against reperfusion injury after myocardial ischemia, primarily due to the extract WS1442. In a study on isolated mesenteric artery of rat with an extract of the fruit, has been documented a vascular relaxing effect. It seems that this effect is due to involvement of nitric oxide (NO). Furthermore, the procyanidins seem to have vasodilatory action with endothelium-dependent mechanism increasing the production of c-GMP: the vascular action would be mediated by nitric oxide (NO) and the degree of activity of potassium channels.
The amines have positive and vasodilatory activity. Some flavonoids seem to play a sedative and antispasmodic activity in the central nervous system by decreasing the excitability.
apigenin
CARDIOVASCULAR ACTION
It 's long been known that the hawthorn is a plant with important cardiovascular activity, experiments on animals and men document his corononaroactive and cardioprotective action.
Studies have shown that the O-glycosides luteonil-7-glucoside, hyperoside and rutin produce marked increase in coronary flow and effect lusitropic positive (increasing the rate of relaxation of the myocardium), as well as increase in heart rate and positive inotropic effect . The actions were independent of action on beta-adrenergic receptors. The authors of this study indicated as a possible mechanism the inhibition of 3'-5'-c-AMP-phosphodiesterase with a consequent increase in cAMP which induces the phosphorylation of proteins (via protein kinase) as a result of an increase of intracellular calcium which leads to increases the strength of contraction. Myocardial effects of flavonoids; during this study were also shown the properties of the monoacetil-vitexin-rhamnoside on reduction of the development tension and its reduced vasodilatation action after the inhibition of EDRF formation by L-nitroarginine. However a more recent German study seems not to confirm the mechanism of action through inhibition of phosphodiesterase. These scholars have set out from the Crataegus lengthens the refractory period in isolated perfused hearts and increases the duration of the action potential of guinea pig papillary muscle. By searching for the mechanisms of action, they would be identified in the block of potassium channels: the magnitude of inhibition is sufficient to justify the increase in duration of action potential. Contrary to expectations, in this study was not found in any activity of calcium channels, which would exclude actions on phosphodiesterase. The action of inhibition of potassium-dependent repolarization in ventricular myocytes is similar to that of class III antiarrhythmic drugs and could be the basis of the antiarrhythmic effects of hawthorn. Crataegus extract blocks potassium currents.
OPCs have also been shown to inhibit ACE, with vasodilator and diuretic effect. Angiotensin converting enzyme (ACE)-inhibitors.
The activity of an extract of hawthorn, WS1442, is important in vasorelaxation via eNOS phosphorylation and relaxation of coronary artery rings through the redox-sensitive Src/PI3-kinase/Akt-dependent phosphorylation of eNOS. NO-mediated vasorelaxation and Endothelium-dependent relaxation via a redox-sensitive Src- and Akt-dependent activation of endothelial NO synthase. It was also demonstrated the ability of anthocyanosides to induce vasodilation especially in splenic and coronary districts. This action is not due to a mechanism of beta-adrenergic type, but rather to an increased release of prostaglandin-acting vasodilator, in particular PGI2, produced by the endothelium vessel. In addition, the anthocyanosides potentiate the coronary vasodilation induced by adrenaline, probably by inhibiting the activity of the enzyme catechol-O-methyl-transferase, responsible for the methylation of catecholamines and therefore of their catabolism, similarly to what are able to do rutin and quercetin.
Some studies show that hawthorn protects the heart against ischemia-reperfusion insult and several experiment are carried out about this. In rats, in fact during ischemia occurs decline of ascorbic acid and LDH levels and during reperfusion there is a sharp increase of this enzyme, which then decreases gradually in the continuation of reperfusion, but without reaching the low levels of the phase of ischemia. Pretreatment with hawthorn significantly reduces the increase of LDH during reperfusion, and this would suggest that this drug helps to preserve the cell membrane of myocardial cells protecting it from ischemic injury. Release of lactate dehydrogenase by the ischemic and reperfused Langendorff heart. It is known that during reperfusion there is an increase of the phenomena of lipid peroxidation, as evidenced by higher levels of malondialdehyde and by the reduction of the activity of superoxide dismutase in the myocardial tissue. The Hawthorn reduces these phenomena, and also protects myocardial cell from histological damage that occur during the phenomenon of ischemia-reperfusion.
A study in the rat has investigated the effect of WS1442 on the operation of the myocardium and on its ability to prevent myocardial ischemia during the phenomenon of ischemia-reperfusion. It was noted that it reduced the s-t segment elevation on ECG, the incidence of ventricular fibrillation and mortality, furthermore the myocardial infracted area was also reduced. The study confirms the cardioprotective action of WS 1442 in the rat, due to its antioxidant action, favoring the production of NO and inhibition on the elastase produced by leukocytes. Extract WS 1442 improves cardiac function and reduces infarct size.
A controlled clinical study evaluated the effect of dry hawthorn extract WS1442 on 1011 patients with heart failure NYHA class 2, the extract was administered orally at a dose of 2 capsules daily for 6 months. At the end of the trial, 83% of patients showed a statistically significant symptomatic improvement, with a reduction in blood pressure and also with a significant increase in ejection fraction and ejection time of echocardiography. In fact, the electrocardiogram showed a reduction in heart rate, s-t depression and extrasystoles statistically significant. Extract WS 1442 in the treatment of NYHA stage II heart failure.
Studies have evaluated the efficacy of the extract WS1442 on exercise tolerance and quality of life in patients with heart failure NYHA class II, leading to an improvement in exercise tolerance and in clinical symptoms, pressure-heart rate product, left ventricular ejection fraction, and patients' subjective sense of well-being. Extract of Crataegus berries on exercise tolerance and quality of life in patients with congestive heart failure.
In a recent investigation,the neuroprotective effect of alcoholic extract of Hawthorn (Crataegus oxycantha) is evaluated against middle cerebral artery occlusion induced ischemia/reperfusion injury in rats, leading to a protection of the brain against ischemia reperfusion. Hawthorn extract reduces infarct volume and improves neurological score.
Nanomechanics and Sodium Permeability of Endothelial Surface Layer Modulated by Hawthorn Extract WS 1442
ANTI-INFLAMMATORY ACTION
One study has documented the activity of Crataegus about inhibition of thromboxane A2 in vitro. In fact it was seen the ability of hydroalcoholic extract of buds of C. O. to inhibit the synthesis of TxA2. Seeking the components responsible for the effect, researchers have focused on two proanthocyanidins, catechin and epicatechin. Inhibition of thromboxane A2 biosynthesis.
The triterpene fraction, especially the cycloartenol, seems to have anti-inflammatory action by inhibition of phospholipase A2. The effects of a triterpene fraction isolated from Crataegus:phospholipase A2 inhibition.
The complement cascade is one of several mechanisms which can lead to vascular damage; flavonoids and OPC prevent damage of the vascular walls also through a mechanism anticomplementary. In a study, the O-glycoside rutin was the most active, quercetin was less active while the C-glycosides (such as vitexin) showed no activity. Proanthocyanidin A-2 and procyanidin C-1 (OPC) showed a strong inhibition of classical path (CP) and of the alternative (AP). The mechanism responsible for these actions seems to be to a chelation of divalent ions Ca (Ca 2 +): without Ca2 + C1r, C1q and C1s can not be complexed to form C1. Anti-complementary activity.
ANTIOXIDANT ACTION
It 's been documented antioxidant activity using different extracts of Crataegus Monogyna in three different experimental models of generation of reactive oxygen species (superoxide anion, hydrogen peroxide and acid ipocloro). The activity, attributed to the total content of phenolic proanthocyanidins and flavonoids, was more pronounced with fresh young leaves and fresh buds rather than dried flowers pharmaceutically prepared. Oxygen species scavenging activity of phenolic extracts from hawthorn.
Antioxidant activities of Crataegus monogyna extracts
LIPID-LOWERING ACTION
Other action attributed to Crataegus is that lipid-lowering. Indian studies have been made which document safe lipid-lowering and antiateromasic action of tincture of Crataegus in rats fed high-fat diet. The mechanism, attributed to the synergistic action of flavonoid components, triterpene and amino, seems to be represented by upregulation of hepatic LDL receptors with modulation of the production / degradation of cholesterol intrahepatic; in fact the hepatic cell membranes of mice treated with tincture of Hawthorn in addition to the atherogenic diet, exhibit a greater number of molecules 125I-LDL, indicating an increased activity of LDL receptors. Effect of tincture of Crataegus on the LDL-receptor activity.
SIDE EFFECTS AND TOXICITY
Hawthorn is safe and its side effects are minimal when consumed in recommended dosages. No changes in blood status, liver enzymes, electrolytes, and glucose or erythrocyte sedimentation rate were observed in a human clinical study of 136 patients treated with 160 mg of the WS 1442 hawthorn extract. There are no reports of adverse effects with low doses but higher doses increase the risk of hypotension and sedation. It should not be used in children under 2 years of age. General symptoms of acute toxicity observed in a number of animal models have been documented as bradycardia and respiratory depression leading to cardiac arrest and respiratory paralysis.
Howthorn extract can act synergistically with digitalis, cardiac glycosides, beta blockers and other hypotensive drugs. It 's possible that it becomes necessary to change the dosages of these drugs, especially patients who are taking digitalis, should reduce the dose required, becouse the hawthorn can have a powerful effect. Crataegus and digoxin.
Cyclophosphamide (CP) is extensively used as an antineoplastic agent for the treatment of cancers, as well as an immunosuppressive agent. However CP can cause several adverse effects including reproductive toxicity. Crataegus monogyna has been shown to be cytoprotective by scavenging free radicals. A study was conducted to assess whether Crataegus monogyna fruits aqueous extract with anti-oxidant properties, could serve as a protective agent against reproductive toxicity during CP treatment in a rat model. These findings indicate that Crataegus monogyna may be partially protective against CP-induced testicular toxicity. Crataegus and Cyclophosphamide.
