Hawthorn: Background. Actions

Historical Note

The name ‘hawthorn’ comes from ‘hedgethorn’, after its use as a living fence in much of Europe. Dioscorides and Paracelsus praised hawthorn for its heart-strengthening properties and it is also known in TCM. It has since been shown to have many different positive effects on the heart and is a popular prescription medicine in Germany for heart failure.

Common Name

Hawthorn

Other Names

Aubepine, bianco spino, crataegi (azarolus, flos, folium, folium cum flore [flowering top], fructus [berry], nigra, pentagyna, sinaica boiss), English hawthorn, Chinese hawthorn, fructus oxyacanthae, fructus spinae albae, hagedorn, hedgethorn, maybush, maythorn, meidorn, oneseed hawthorn, shanzha, weissdorn, whitehorn

Botanical Name / Family

Crataegus laevigata, Crataegus cuneata, Crataegus oxyacantha, Crataegus monogyna, Crataegus pinnatifida (family Rosaceae [Rose])

Plant Parts Used

Extracts of the leaf and flower are most commonly used, although the fruit (berries) may also be used.

Chemical Components

Leaves and flowers contain about 1% flavonoids, such as rutin, quercitin, vitexin, hyperisise, 1-3% oligomeric procyanidins including catechin and epicatechin, triterpenes, sterols, polyphenols, coumarins, tannins. Although the therapeutic actions cannot be attributed to single compounds, the herb has been standardised to flavonoid content (hyperoside as marker) and procyanidins (epicatechin as marker). RP WS 1442 is a hydro-alcoholic extract of hawthorn prepared from leaves and blossoms and standardised to 18.75% oligomeric procyanidins. It has been found that bioequivalent extracts as determined by noradrenaline-induced contraction of isolated guinea pig aorta rings can be obtained using 40-70% ethanol or methanol as the extraction solvent, whereas aqueous extracts had markedly different constituents and pharmacological effects.

Main Actions

CARDIOVASCULAR EFFECTS

Hawthorn has been extensively studied, and there is good research evidence to support cardiovascular actions that include increasing the force of myocardial contraction (positive inotropic action), increasing coronary blood flow, reducing myocardial oxygen demand, protecting against myocardial damage, improving heart rate variability, as well as hypotensive and antiarrhythmic effects. Hawthorn therefore differs from other inotropic agents, which reduce the refractory period and increase the risk of arrhythmias.

In vitro studies using isolated frog and guinea pig heart preparations, as well as in vivo studies on dogs and cats, report increased myocardial contractility and stroke volume. In vitro and in vivo studies on rats report an antiarrhythmic action and a significant cardioprotective effect during cardiac ischaemia.

Hawthorn flavonoids have also been shown to decrease the cytotoxicity of hypoxia to human umbilical vein endothelial cells in vitro, as well as protect against delayed cell death caused by ischaemia/reperfusion brain injury in gerbils. These effects have been attributed to improving energy metabolism, scavenging oxygen free radicals and inhibiting production of free radicals in ischaemic myocardium.

Dose-dependent increases in coronary blood flow have been shown in isolated human coronary arteries and it has been suggested that this is caused by membrane hyperpolarisation of vascular smooth-muscle cells due to potassium channel activation. Other in vitro evidence suggests that phosphodiesterase inhibition may underlie the myocardial action of hawthorn.

Much of hawthorn’s cardiovascular activity is attributed to its flavonoid constituents and hawthorn extract is classified as a flavonoid drug in Germany. Studies using isolated guinea pig hearts suggest that the oligomeric procyanidins contribute to the vasodilating and positive inotropic effects of hawthorn, and ischaemia-reperfusion studies in rats suggest that these compounds are also responsible for cardioprotective effects.

Several procyanidins have shown ACE inhibition in vitro, in a reversible and non-competitive manner. Although the original study identifying this activity tested isolated procyanidins from another herb, they are found in relatively high concentration in hawthorn extracts.

ANTIOXIDANT

It has been suggested that the part of the mechanism for hawthorn’s cardiovascular protective effects may be due to protection against human LDL from oxidation or indirect protection via maintenance of alpha-tocopherol, as hawthorn extract has been found to possess antioxidant activity in vitro with effective inhibition of oxidative processes, efficient scavenging of 02-and possible enhancement of glutathione biosynthesis.

Hawthorn’s free radical scavenging capacity is considered to relate to its total phenolic proanthocyanidin and flavonoid content. This is supported by a study that demonstrated that the capacity of hawthorn extracts to inhibit Cu2+-induced LDL oxidation is linked to their content in total polyphenols, proanthocyanidins (global and oligomeric forms), as well as to their content of two individual phenolics: a flavonol, the dimeric procyanidin B2, and a flavonol glycoside, hyperoside. The highest antioxidant activity appears to be found in the flower buds, which are high in proanthocyanidin content, and the leaves, which are high in flavonoid content.

LIPID-LOWERING

The monomeric catechins and oligomeric procyanidins are thought to contribute to a hypocholesterolaemic effect. This may occur through a variety of mechanisms including an upregulation of hepatic LDL receptors, enhanced degradation of cholesterol to bile acids and suppression of cholesterol biosynthesis, as well as inhibition of cholesterol absorption mediated by downregulation of intestinal acyl CoA:cholesterol acyltransferase activity.

A traditional multi-herbal Chinese formula containing hawthorn has been found to prevent experimental hypercholesterolaemia in rats, probably due to its choleretic function. A different multi-herbal Chinese formula was also found to protect vascular endothelial cells from excess cholesterol in vivo.

ANTIVIRAL

The O-glycosidic flavonoids and the oligomeric proanthocyanidins exhibited significant inhibitory activity against herpes simplex virus type 1 in vitro.

ANTI-INFLAMMATORY

Flavonoids from hawthorn have demonstrated anti-inflammatory and hepatoprotective activity in vitro and in vivo. It is thought that this is achieved by reducing the release of PGE2 and NO in vitro, as well as decreasing the serum levels of the hepatic enzyme markers, reducing the incidence of liver lesions, such as neutrophil infiltration and necrosis, and decreasing the hepatic expression of iNOS and COX-2 in vivo.

A hydro-alcoholic extract from the flower heads of C. oxyacantha has also been found to inhibit thromboxane A2 biosynthesis in vitro.

Hawthorn fruit has been shown to be protective in experimental models of inflammatory bowel disease in mice with restoration of body weight and colon length, increased haemoglobin count, reduced signs of inflammation, such as infiltration by polymorphonuclear leukocytes and multiple erosive lesions, along with improved survival.

Other Actions

Hawthorn may decrease uterine tone and motility and exert antispasmodic and analgesic effects. The high procyanidin content in the herb provides a theoretical basis for other actions such as antimicrobial, anti-allergic and collagen-stabilising effects.

An aqueous extract of hawthorn leaves exhibited hypoglycaemic activity in streptozotocin-diabetic rats, but not in normal rats, without affecting basal plasma insulin concentrations. Hawthorn has also been found to have hepatoprotective effects in rats with myocardial infarction, with protection against alterations in tissue marker enzymes of experimentally induced liver injury and a reversal of histological changes. A multi-herbal Chinese medicine formula containing hawthorn reversed alcohol-induced fatty liver and liver damage in rats.