HERBAL MEDICINE

CHANG ET
HERBAL
HAWTHORN
MEDICINE
AL

Hawthorn
Qi Chang, PhD, Zhong Zuo, PhD,
Francisco Harrison, MD, and Moses Sing Sum Chow, PharmD

A review with 54 references covers all aspects of hawthorn,

the genus Crataegus, including its traditional uses, chemical
constituents, pharmacological activities, and clinical effects.
Although the effectiveness of hawthorn on the treatment of
cardiovascular diseases has received extensive attention

worldwide, further scientific research on various areas such

as pharmacokinetics, mechanism of actions will be necessary to ensure its safe and effective usage.
Journal of Clinical Pharmacology, 2002;42:605-612
2002 the American College of Clinical Pharmacology

proving blood circulation, and removing blood stasis.

Thus, they are used in prescriptions to treat indigestion
with epigastric distension, diarrhea, and abdominal
pain; amenorrhea; hypertension; and hyperlipidemia.8
In Europe, hawthorn fruits, leaves, flowers, or a
combination thereof have been traditionally used as an
astringent, antispasmodic, cardiotonic, diuretic,
hypotensive, and antiatherosclerotic agent.3 The herb
is used to treat various heart problems, including
heart failure, New York Heart Association (NYHA)
stages I-II, angina pectoris, hypertension with myocardial insufficiency, mild alterations of cardiac rhythm,
and atherosclerosis.8
Both in China and Europe, hawthorn fruit is consumed not only for medicinal purposes mentioned
above but also as foodstuff (e.g., canned fruit, jam, jelly,
drink, and wine).3

awthorn, a common name of all plant species in

the genus Crataegus, is a thorny shrub or small
tree that normally has bright green leaves, white flowers, and bright red berries (Figure 1), each containing
one to three or five seeds, depending on the species.1
Hawthorn is a member of the Rosaceae family and is
recognized to have approximately 280 species primarily from northern temperate zones in East Asia, Europe,
and eastern North America.2,3 It is a widely used herb
for preventing and treating cardiovascular diseases.
At present, more than 20 species of hawthorn are
used as herbal drugs or drug materials in the world.4
Some of them are officially listed in the pharmacopoeias of many countries such as China, Germany, France,
and England (Table I).
HISTORY AND TRADITIONAL USES
Hawthorn has a long history of use in traditional Chinese medicine (TCM) and European herbal medicine. It
was first mentioned for TCM in Tang Ben Cao,5 the
worlds first official pharmacopoeia in 659 A.D. In Europe, the use of hawthorn can be dated back to the time
of Dioscorides in the first century A.D.6 Its use for the
treatment of heart disease began in the late 1800s.7
In TCM, hawthorn fruits are used for stimulating digestion and promoting the function of the stomach, imFrom the School of Pharmacy, Chinese University of Hong Kong, Shatin,
New Territories, Hong Kong, SAR, PRC (Dr. Chang, Dr. Zuo, Dr. Chow) and
Harrison Clinical Research, Mnchen, Germany (Dr. Harrison). Submitted
for publication December 15, 2001; revised version accepted February
16, 2002. Address for reprints: Dr. Zhong Zuo, School of Pharmacy, Chinese University of Hong Kong, Shatin, N.T. Hong Kong.

J Clin Pharmacol 2002;42:605-612

CHEMICAL CONSTITUENTS
Hawthorn fruits, leaves, and flowers contain a number
of chemical constituents, such as flavonoids (0.1%-1%
in fruits, 1%-2% in leaves and flowers),9-11 oligomeric
proanthocyanidins (OPCs, 1%-3% in fruits or leaves
with flowers),10,12,13 triterpene acids (0.5%-1.4% in
fruits),3 organic acids (2%-6%),14 sterols, and trace
amounts of cardioactive amines.15 Among these,
flavonoids and OPCs are the two major groups of
bioactive components. Many hawthorn preparations
are standardized based on their flavonoid and OPC
contents. Specific compounds and their structure, representative of the main chemical groups, are shown in
Figures 2 to 5.

605

CHANG ET AL

effect, increase of coronary blood flow and cardiac

output, and reduction of oxygen consumption.16-20
These actions may be related to phosphodiesterase
inhibitory effect.20,21
Antiarrhythmic Activity
Hawthorn extracts from fruits or leaves with flowers
have also been found to protect against heart
arrhythmias induced by aconitine, calcium chloride,
and chloroform-adrenaline in various in vitro and in
vivo rat experiments.22-24
Hypotensive Activity
When flavonoid, OPC, and triterpene acid extracts
were administrated intravenously to various species of
animals, prolonged dose-dependent hypotension in
anaesthetized normotensive and hypertensive animals
was observed.24-28 The hypotensive action was mainly
attributed to peripheral vasodilation.29 In more recent
studies, the hawthorn extract was found to induce endothelium-dependent relaxation in an isolated rat
mesenteric artery.30 Procyanidins were identified as the
major component for this effect.31
Hypolipidemic Activity
Figure 1. Photographs of a hawthorn tree (Crataegus pinnatifida
Bge. var. major N.E. Br.) (upper and left lower) and the Chinese medicine Shan Zha (right lower). Extracted from Zhonghua Renming
Gonghegou Yaodian, Zhongyao Caise Tuji, 1995.

PHARMACOLOGICAL ACTIVITIES
The main pharmacological activities are primarily
cardiovascular. These include cardiotonic,
antiarrhythmic, hypotensive, hypolipidemic, and
antioxidative activities.
Cardiotonic Activity
Numerous in vitro and animal studies have tested the
activities of water-soluble extract, flavonoid fraction,
triterpene fraction, and OPC fraction, which are prepared from hawthorn fruits, leaves, or flowers as well
as individual components of hawthorn (hyperoside,
luteolin-7-glucoside, epicatechin, vitexin, and
rutin). Marked cardiotonic actions have been observed: positive inotropic and negative chronotropic

606 J Clin Pharmacol 2002;42:605-612

Hawthorn has been found to decrease the serum levels

of cholesterol, LDL-cholesterol, and triglyceride in
hypercholesterolemic and atherosclerotic animals. It
also significantly inhibits lipid deposition in the liver
and aorta.32-35 When administered to rats fed with an
atherogenic diet, the hawthorn fruit extract increased
excretion of bile acid, depressed hepatic cholesterol
synthesis, and significantly increased the binding of
125
I-LDL to the liver plasma membranes, indicating an
enhancement of the LDL-receptor activity.36
Antioxidative Activity
In some in vitro studies, various hawthorn extracts
from fruits, leaves, or flowers possess antioxidative activity.9,37 These activities are likely to be related to OPCs
and flavonoids, as individual OPCs and flavonoids,
such as epicatechin, rutin, hyperoside, and
isoquercitrin, have shown a strong inhibitory effect
against human LDL oxidation.38
In various in vivo studies, an alcoholic extract has
been found to produce a protective effect on oxidative
stress in experimental atherosclerotic rats.32 The extract prevented the increase of lipid peroxidation and

HAWTHORN

Table I Some Species of Hawthorn Officially Used as Herbal Drug or Drug Materials Worldwide
Pharmacopoeias

Chinese Pharmacopoeia (English ed., 1997)

European Pharmacopoeia (1998)
British Pharmacopoeia (2000)
German Pharmacopoeia (DAB, 1997) and Swiss
Pharmacopoeia (1997)

France Pharmacopoeia (1998)

Species Accepted

C. pinnatifida Bge.
C. pinnatifida Bge. var. major N.E. Br.
C. oxyacantha L.
C. monogyna Jacq.
C. oxyacantha L.
C. monogyna Jacq.
C. oxyacantha L.
C. monogyna Jacq.
C. pentagyna Waldst.
C. nigra Waldst.
C. azarolus L.
C. oxyacantha L.
C. monogyna Jacq.

Parts Used

Fruits
Fruits, flowers
Fruits, leaves, and flowers
Leaves with flowers

Leaves with flowers

Figure 4. The chemical structures of representative triterpene acids

in hawthorn.
Figure 2. The chemical structures of representative flavonoids in
hawthorn.

Figure 5. The chemical structures of representative organic acids in

hawthorn.

Figure 3. The chemical structures of representative proanthocyanidins in hawthorn.

ized the levels of antioxidant enzymes in the liver,

aorta, and heart tissue32 and increased the activity of
superoxide dismutase (SOD) in hyperlipidemic rats39
or mice.40
Pharmacokinetics

the decrease of glutathione and alpha-tocopherol content in the liver, aorta, and heart tissues. It also normalHERBAL MEDICINE

So far, no pharmacokinetic study has been reported

with any hawthorn active components after consumption of the hawthorn herb or its preparations.
607

608
Table II Some Clinical Studies on Hawthorn Preparations for Treatment in Patients with Cardiovascular Diseases
Jadad
50
Score
(max: 5)

Number
of
Patients

Randomized,
placebo
controlled
double blind
Open trial

136

30

Randomized,
placebo
controlled,
double blind
Randomized,
placebo
controlled,
double blind

44

45

Reference

41

34

42

43

Plant
Parts
Used

Dosage

New York Heart

Association
(NYHA) stage II
heart failure
Hyperlipidemia

Leaves
with
flowers

85

Randomized,
placebo
controlled,
double blind
Placebo
controlled,
double blind

Study
Design

Patient
Type

Duration
(weeks)

Assessment
Methods

Results
(for hawthorn group)

One capsule (80 mg

extract [5:1, 18.75%
OPCs]), bid

Bicycle
ergometry
exercise

Fruits

250 ml drink (0.56

mg flavones per
100 ml) bid

4.3

Serum
lipid
analysis

NYHA stage II
heart failure

Leaves
with
flowers

300 mg extract (3:1,

2.2% flavonoids) daily

Bicycle
ergometry
exercise

78

NYHA stage II
heart failure

Leaves
with
flowers

200 mg extract (3:1,

2.2% flavonoids) tid

Bicycle
ergometry
exercise

132

NYHA stage II
heart failure

Leaves
with
flowers

300 mg extract (3:1,

2.2% flavonoids) tid

Bicycle
ergometry
exercise

30

NYHA stage II
heart failure

Leaves
with
flowers

One capsule (80 mg

extract [5:1, 18.75%
OPCs]) bid

Bicycle
ergometry
exercise

A significant advantage in postexercise

pressure/heart rate product, heart
rate, and subjective patient
symptomatology.
Significantly decreased serum
cholesterol (p < 0.001), LDL-C, and
triglyceride compared with that before
treatment. Significant malondialdehyde reduction showed strong
antioxidative effect.
Exercise tolerance, pressure/heart rate
product, and clinical symptomatology
all showed a trend toward superiority
but were not statistically significant.
Statistically significant improvements
in working capacity, systolic blood
pressure, and heart rate during
exercise. No effect on diastolic blood
pressure.
Effective in decreasing heart rate and
in improving exercise tolerance and
pressure/heart rate product. The
severity of symptoms dropped by
50%. No effect on blood pressure.
Significant advantage in increase of
heart work capacity, reduction of
heart rate, improvement in
pressure/heart rate product, and mild
reduction of systolic and diastolic
blood pressures.

46

Randomized,
placebo
controlled,
double blind

40

NYHA stage II
heart failure

Extract of 2 ml, tid

hawthorn
and
passionflower

Walking
and
bicycle
ergometric
tests

47

Placebo
controlled,
double blind

46

Angina
pectoris

Fruits

300 mg extract
daily

48

Randomized,
placebo
controlled,
double blind

60

Angina pectoris
(NYHA stages I
and II heart
failure)

Leaves
with
flowers

60 mg extract (5:1,
18.75% OPCs) tid

Bicycle
ergometry
exercise

49

Randomized,
placebo
controlled,
double blind

80

NYHA stage II
heart failure

Leaves
and
fruits

180 mg extract (5:1,

18.75% OPCs) daily

Bicycle
ergometry
exercise

Slight but significant improved

exercise capacity (about 10% above
baseline), decrease in resting heart
rate, diastolic blood pressure at rest,
and total serum cholesterol and
low-density lipids.
A significant improvement was
observed in the hawthorn group, with
84.8% of the antianginal effective rate
and 46.4% of the ECG effective rate.
A significant reduction in the
incidence of myocardial ischemia and
a 25% improvement in exercise
tolerance, increasing coronary
perfusion and economizing myocardial oxygen consumption. No side
effects.
A statistically significant improvement in general well-being, cardiac
function, dyspnea, palpitation. Slight
but significant improvement in
lowering blood pressure. No
differences were noted in improvement of the ECG compared with
control group.

609

CHANG ET AL

CLINICAL STUDIES
Hawthorn preparations are potentially useful for early
stages of congestive heart failure, hypertension, angina,
and minor arrhythmia. This has been demonstrated in
many clinical studies (see Table II).34,41-49 These results
showed that hawthorn was effective in decreasing
heart rate, improving exercise tolerance and pressure/heart rate product, and lowering serum lipids in
patients with NYHA stage II heart failure or with
hyperlipidemia. But in some of these studies, no effect
on diastolic blood pressure was observed.43,44 Although
serum lipids in the patients with hyperlipidemia were
reduced by hawthorn in one clinical trial,34 the study
was not controlled. Thus, the clinical benefit of this effect requires further confirmation.
DOSAGES
Hawthorn is a slow-acting herb and should be used for
at least 4 to 8 weeks for full benefit. The dosage depends on the type of preparation and source material.
Doses tested in European clinical studies ranged from
160 mg to 900 mg a day of hawthorn extract, which is
standardized to contain 2.2% of flavonoids or 18.75%
of oligomeric proanthocyanidins. Most commonly
used dosage forms and dosage are the following:
In Europe:
Standardized extract: 120 to 240 mg, three times a day51
51
Tincture (1:5): 2 to 4 ml, three times a day
Tea: 1 to 2 teaspoons of fruits soaked for 15 minutes in 1
51
cup of water
In China:
9 to 12 g of dried fruit, two or three times a day, used in
hawthorn prescriptions or its products such as extract,
8
tincture, or pill

SIDE EFFECTS, TOXICITY, AND

DRUG INTERACTIONS
No significant adverse events have been reported in
clinical trials.
The acute toxicity (LD50) is 18.5 ml/kg in mice and
33.8 ml/kg in rats by oral administration of a 10% alcoholic extract solution of hawthorn leaves and fruit52
and 1.56 g/kg of the flavonoids fraction in mice intravenously.53 LD50 of the proanthocyanidins fraction is 130
mg/kg by i.p. and 300 mg/kg by s.c. in mice.54
Hawthorn may have a potentiating effect on digitalis, beta-blockers, and other hypotensive drugs. Modification of the drug dosage may be required.55,56 This

610 J Clin Pharmacol 2002;42:605-612

potential drug interaction may be related to the

cardiotonic and hypotensive effects of hawthorn.
SUMMARY
Hawthorn (Crataegus species) has long been regarded
as a digestive and cardiotonic in traditional Chinese
medicine and European herbal practice. The main constituents of hawthorn are flavonoids, triterpene acids,
proanthocyanidins, and organic acids. Various animal
studies have suggested that hawthorn extracts exert a
wide range of pharmacological properties, especially
on the cardiovascular system, including cardiotonic,
antiarrhythmic, hypotensive, hypolipidemic, and antioxidant activities. These beneficial effects are mainly
attributed to its flavonoid and proanthocyanidin components. Numerous clinical studies have demonstrated that hawthorn preparations are very effective in
early stages of congestive heart failure, hypertension,
angina, and minor arrhythmia. Hawthorn is currently
used widely by practitioners and individuals in various parts of the world for the treatment of heart failure,
hypertension, atherosclerosis, angina pectoris, indigestion, and abdominal distention.
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