In both the East and West, hawthorn has been used for millenia as both a food and a medicine. Today hawthorn preparations are used extensively in France, England, Germany, Russia, and other European countries, especially for the treatment of heart and cardiovascular ailments.

BOTANY

Taxonomy

Crataegus is a genus of the Rosaceae (rose family), with approximately 280 species native to northern temperate zones primarily concentrated in East Asia, Europe and Eastern North America. Some species are found in central and southwestern Asia. The vast majority of the North American species occur in the eastern regions, from Newfoundland to mountains of northern Mexico (Sargent 1933).

Hawthorn is a highly complex and technical plant group. W.H. Duncan and M.B. Duncan (1988) note that Crataegus is difficult to define in terms of numbers and species because of hybridization and unusual factors relative to reproduction, including 1) apomixis, or the development of an embryo from cells other than sex cells; 2) polyploidy, where chromosome numbers are increased by 1,2,3,4-fold or more; and 3) anauploidy, in which chromosome numbers are in multiples other than those involved in polyploidy.

A number of species are valued for economic use as food, medicine, and ornamentals. Crataegus laevigata (Poir.) DC. (C. oxyacantha auct. non. L.) English Hawthorn, Haw, Whitethorn, or aubepine (French) is widely used as a source plant for Crataegus drugs. Crataegus laevigata is the C. oxyacantha of ancient Latin authors. The two are often confused. Crataegus oxyacantha L. is most commonly listed as the source plants for hawthorn preparations. Crataegus monogyra Jacq. also is used for production of hawthorn fruits. Crataegus pinnatifida Bge., C. pinnatifida var. major N.E. Br., and C. cuneata Sieb. et Zucc. are used as source plants for the Chinese drug Shan-zha (dried hawthorn fruit). These three taxa are official in the Pharmacopeia of the People's Republic of China (Mabberly 1988, Tucker et al. 1989, Lou 1987, Pharmacopeia Committee 1985).

Crataegus laevigata occurs in much of northern Europe and has become naturalized in eastern North America and India. It was brought to North America by early European colonists as an ornamental, primarily as a hedge plant. American species were also introduced to Europe at an early date (Emerson 1875). The Chinese C. pinnatifida is also found in European and American horticulture. Crataegus pinnatifida var. major is distributed in north and northeast China, where most of the supply is cultivated. Crataegus pinnatifida is distributed in northeast China, north China, Shanxi and Jiangsu provinces. The former taxa are known as "Northern Hawthorn" fruits. Chief production provinces include Shangdong, Henan and Hebei. Crataegus cuneata, known as "Southern Hawthorn," is primarily distributed in the Changjian valley in Guangdong and Guangxi provinces. Major production areas include Zhejiang and Jiangsu provinces (Lou 1987).

Description

Crataegus species are much-branched shrubs or small spreading trees, usually (though not always) armed with long slender thorns. The deciduous leaves are simple, usually ovate to elliptical, pinnately veined, serrate, dentate, or with shallow-lobed margins. Leaves are larger and more lobed on young branchlets.

Flowers are usually produced in spring on simple or branched terminal corymbs, sometimes singly or in clusters of twos or threes. The perfect, radially symmetrical flowers have 5 petals, often pink in bud, then turning white or pink in full bloom, and 5 sepals persistent following anthesis. The yellowish-green to yellow, orange, or, more commonly, red globular fruits, are a berrylike pome with 1-5 small one-seeded nutlets. The flesh is dry-firm to succulent. In one species, Blueberry Hawthorn, C. brachycantha Sarg. & Engelm., the fruits are bright blue and glaucous. (Godfrey 1988, Little 1980, Duncan and Duncan 1988.)

Descriptions of the genus are relatively vague at best. According to Eggleston (1908), "The genus is so variable that it is impossible to find characters which will hold absolutely true, either between species or even sections; then again, characters which seem to hold good in one section are useless in the next." (Eggleston, 1908, p. 74.)

NOMENCLATURE

Dioscorides, the most reliable of the ancient authors on plant medicines, called Crataegus "Oxuakantha," which was retained by Linnaeus in the name C. oxyacantha, an old name for C. laevigata. Although many botanical and herbal writers from the 15th through the 17th centuries took Dioscorides' Oxuakantha to be a kind of Crataegus, Parkinson (1640) determined that it was likely a Pyracantha. It is listed as C. pyracantha in Gunther's edition of Dioscorides (1933). The Oxuakantha described by Dioscorides is now referred to as Pyracantha coccinea (Crataegus pyracantha) (Pickering 1879, L.H. Bailey Hortorium 1976). Pyracantha is a genus not particularly lauded for its healing properties. Galen's "Oxyacanthus" is also certainly a Pyracantha, Pyrus or Mespilus (medlar). The latter three genera are closely allied and until the 17th century were likely to be poorly distinguished from Crataegus (Parkinson).

Theophrastus (Hort), the most important Greek writer on botany describes a type of hawthorn (C. laevigata according to Hort) as a kind of medlar (Mespilus) under the name "Anthedonoeides." Pliny (Jones), a great compiler who was not above plagiarising from other sources, said this of the plant:

By crataegos or crataegon Theophrastus would have us understand the tree which in Italy is called aquifolium.

Gerard (1633) called hawthorn oxyacanthus, white thorne, or hawthorn tree. The latter two, and the name "May-Bush," are still common in England. In Germany hawthorn is now called Weiádorn (White Thorn), while in France it is referred to as l'epine noble (the noble thorn) because it was supposedly used for Christ's crown of thorns. Crataegus species are also variously known as Hawthorn, Haw, Thornapple (Ed. note -- not to be confused with Datura), Red Haw, Hog-apple, and many other common names. Haw is derived from an ancient word referring to hedge. The generic name Crataegus, derived from the Greek Kratos, meaning strength, in reference to the hardness of the wood, is attributed to Theophrastus. The specific epithet, "oxyacantha," attributed to Disocorides, is a Greek name that has been applied by ancient writers to barberry, sweetbriar, hawthorn, and other plant groups. Oxy means sharp and acantha, a thorn (Alcock 1876).

HISTORY OF USE

The history of the medicinal use of hawthorn seems to be relatively short. As detailed above, it is doubtful if the ancients wrote about hawthorn. It is not mentioned in the late Latin works Herbarium Apuleii Platonici (1000-1050) or Macer Floridus (8491112), or the early Anglo-Saxon herbals (Cockayne), such as the Leechbook of Bald or Lacnunga from 900-1100 A.D. In the Arabian school, C. azarolus L., a Mediterranean hawthorn, is mentioned by Al-Samarqandi (ca. 1210 A.D.) as being "useful for the stomach and yellow gall" (Levey & Al-Khaledy).

In the late 16th and early 17th centuries it was mentioned in Parkinson and Gerard. Gerard noted (1597) only that the fruits are very astringent, and quoted Dioscorides's discussion of Pyracantha coccinea, which does not concern hawthorn proper. Parkinson (1640) wrote about the ripe berries or the seeds being "a singular good remedy against the stone" (kidney stones), or taken in wine for dropsy, saying also that the flowers steeped in wine" is a soveraigne remedy for the plurisie."

According to Sowerby, school children in late medieval England gathered hawthorn branches for the maypole which they danced around during the May festival in honor of Flora. This custom was preserved in Europe through the 1800s. The Romans also used hawthorn's hard wood for carving and making walking sticks.

Over the centuries legends about hawthorn have abounded in England and Europe. The poets, too, have sung its praises, as in Chaucer's phrase:

Marke the faire blooming of the Hawthorne tree

Who finely cloathed in a robe of white,

Fills full the wanton eye with May's delight.

Goldsmith, in his "Deserted Village," penned these well-known lines:

The Hawthorn-bush with seats beneath the shade,

For talking age and whispering lovers made.

It appears that the current use of hawthorn for heart conditions dates back to the 17th century, according to Leclerc (Madaus), though in 1733, Alleyne in his The New English Dispensatory writes only of its use as a diuretic and"powerful expeller(s) of the stone and gravel." He states further that the flowers were the main ingredient in the famous "nephritic water." Green, an Irish doctor, is known to have used it extensively for heart ailments and, after his death in 1894, it is said to have become a famous remedy for this purpose. In Europe, both homeopathic and allopathic doctors used the herb for various heart and cardiovascular ailments from the late 19th through the early 20th centuries -- and with great clinical success. Hawthorn had entered American clinical practice by 1896 (Madaus).

Assmann (Madaus), a homeopathic doctor, said the following regarding hawthorn's use as a cardiac medicine:

Crataegus is no panacea, but for the handling of chronic illness, it is much more suitable than digitalis and strophanthus, because it has no unpleasant side-effects and no cumulative effects. Its success can be achieved if the tincture of the fresh ripe fruit in a suitable dose (3 times daily 10-20 drops after meals) is prescribed.

In North America, Crataegus species were first observed by the Jacques Cartier expedition to Canada of 1535-6. Many "thorns" were observed including hawthorns, which were compared to the European medlars. Subsequent English and French expeditions to the New World in the late sixteenth and early seventeenth centuries noted the presence of "medlars" larger than those in Europe (Erichsen Brown 1979).

Rafinesque (1830) mentions Crataegus. He writes, "Fruits of several edible, red or yellowed, acid, or sweetish, making fine stomachic preserves, useful for diarrhea and antiemetic; such as Cr. coccinea, Cr. tomentosa, Cr. crusgalli. The leaves and flowers of this last, used as pectoral in coughs and whooping cough, as a tea..." (Rafinesque, 1830, p. 213.)

In his ethnobotanies of the Meskwaki, Ojibwe, and Potawatomi, H.H. Smith mentioned a number of medicinal uses, including the use of the fruits for bladder ailments, the tea for pain in the side, and bladder troubles, general debility, and as a medicine for stomach complaints (Erichsen-Brown 1979).

Except for passing references, hawthorns are largely absent from the materia medica of nineteenth century America, until the publication of an article by J.C. Jennings of Chicago in 1896. According to J.U. Lloyd (1917) this is the first conspicuous American reference to the use of Crataegus in the treatment of heart disease. Lloyd writes:

"A well-known physician, the late Dr. Green, of Ennis, County Clare, Ireland, attained an extended reputation in the treatment of `Heart Disease,' keeping the remedy a secret. Upon his death, in 1894, his daughter revealed the fact that this `famous' cure was a tincture of the ripe berries of Crataegus Oxycanthus." (J.U. Lloyd 1917. p. 2.)

Following the publication of Jennings's 1896 paper in the New York Medical Journal, a number of physicians engaged the services of Lloyd Brothers to introduce a preparation of the ripe fruits of hawthorn to the medical practice. They investigated numerous species of Crataegus and made several preparations, including tincture of European hawthorn berry and tinctures of the bark and root. Lloyd claims to have found that one American species was superior to that of the imported C. laevigata (C. oxycantha). Unfortunately Lloyd does not reveal the identity of the American species used in the Lloyd Brothers preparations. The species name is also not given on the Lloyd Brothers product label, which states:

"Specific Indications and Uses: Functional and organic heart affections, with pain, dyspnea, precordial oppression, rapid and feeble heart-action; valvular insufficiency; cardiac hypertrophy; marked anemia; venous stasis; angina pectoris; endocarditis following inflammatory rheumatism." (Anon. 1927)

A number of articles from the medical literature from 1896 1916, including case histories, are reproduced in the Lloyd Brothers Treatise on Crataegus (Lloyd 1917).

While mentioned in early texts for use as a diuretic, astringent, or in the treatment of dyspepsia, historical references to the cardiac-affecting properties of hawthorn fruits are absent from the literature prior to 1896. In the first two decades of this century, numerous articles and case histories on the use of hawthorn in heart disease appeared in medical textbooks and the periodical literature, primarily of Eclectic physicians. Crataegus is barely mentioned in passing in official medical texts such as The United States Dispensatory and is absent in the United States Pharmacopeia. The fruits of three taxa are official in the Pharmacopeia of the People's Republic of China.

The Chinese drug Shan-Zha is first mentioned in the Tang Ben Cao (659 A.D.), attributed to Su Jing and 23 other scholars. Published during the Tang dynasty (618-907 A.D.), it is considered the world's earliest officially published pharmacopeia (Hsu 1986, Hou 1977). In Chinese tradition the fruits are used to improve digestion, eliminate stagnated food, and blood stasis, in the treatment of dyspepsia, lack of milk secretion, fullness in the stomach, abdominal distention, menorrhalgia, postpartum abdominal pain due to blood stasis, and hyperlipemia (Lou 1987).

CULINARY USES AND REGULATORY STATUS

In medieval England, children ate the plant's fruit, which was considered to be very nutritious. The fruit was also used in Russia to make wine (Sowerby). In some regions of Europe the dry pulp of the fruits of C. laevigata and C. monogyna has been eaten or added to flour. In West Asia, the larger, more fleshy and flavorful fruits of C. aronia (L.) Bosc. (C. azarolus) are commonly harvested from the wild and eaten fresh. These two species are variable. In their native ranges, seed from superior forms is selected and planted at field edges or on non-arable land.

The fruits are collected from the mountains around Peking and other parts of China and mixed with sugar to make a jam or jelly or a sweet wine. These, along with candied fruit slices, are commonly sold in markets and by street vendors. The sweet and sour flavor is thought to support and activate the digestion (Lu, Smith & Stuart, Hooper).

The nutlets of C. laevigata and C. monogyna have been found at a number of archeological sites in Europe, from the Neolithic to Roman time. Crataegus aronia seeds have been found in Bronze Age sites in Israel, as well as other archeological sites in the Near East (Zohary and Hopf 1988).

At least a dozen species of Crataegus are documented as food plants of various native groups of North America. Often the fruits were dried and stored for winter use. For an enumeration of native groups that used hawthorn as food, plus references, see E. Yanovsky (1936).

English or May Hawthorn (C. oxyacantha L.) is listed in a now-outdated FDA Policy Guideline as an "herb of undefined safety." (FDA Internal Memo, Nov. 19, 1975.) Currently, hawthorn leaves and berries have no official regulatory status in the U.S.

CHEMISTRY AND PHARMACOLOGY

In the case of hawthorn, the discovery and characterisation of isolated constituents was closely associated with research on their pharmacological activities. For this reason, the chemistry and pharmacology sections are here combined.

Early Work (1850-1960)

The first chemical analyses of hawthorn were performed on the European species (C. laevigata, C. monogyna, and occasionally C. pentagyna), and focused on the fruits and flowers, which have been considered the most active parts since the middle of the 19 th century.

Wicke isolated trimethylamines from the flowers of hawthorn as early as 1854, which Madaus reported and claimed to play a possible role in hawthorn's activity (Madaus). However, recent work on the cardioactive amines of C. laevigata shows that they quickly break down in the digestive tract and thus are probably inactive in oral preparations (Wagner & Grevel, 1982). As early as 1897, Madaus also reported on the peripheral vessel effects of quercitrin and quercetin, the latter being a common flavonoid discovered in hawthorn.

In 1927, Baechler reported (Bersin & Müller) that the effective constituent of the fruits was crataegus acid, which was later found to be a mixture of triterpene carboxylic acids. Schimert asserted that these carboxylic acids were responsible for the coronary dilating effects of hawthorn (Nikolov, 1969), though several later investigations failed to support his claim (Nikolov, 1969; Sajner).

The first compound that proved to be cardioactive in test animals was heptahydroxyflavane glycoside (Nikolov, 1969). It is noteworthy that most early and later work on hawthorn was conducted on animals, not humans. This is surprising considering that hawthorn has shown extremely low toxicity in every animal species tested. There is a need for more practical information about hawthorn's effects on the human cardiovascular system.

The early experiments on Crataegus extracts used intravenous, intraperitoneal, or, rarely, subcutaneous injections of various flavonoid fractions (either water, methanolic, or ethanolic extracts) into the usual array of test animals -- dogs, frogs, mice, rats, guinea pigs, cats, etc. Only a few tests involved oral administration. The general results of these studies are shown in Table 1, summarized from Ammon and Händel (1981b,c). It should be noted, however, that the injection of alcohol (EtOH) itself can lead to vasodilation of the coronary arteries, increasing blood flow to the heart (Kanno, et al.). Thus, tests performed with ethanolic or methanolic extracts must be examined closely regarding any such effects.

These data are, of course, more pertinent to clinical applications in Europe, where injectable preparations of Crataegus extracts are available. In this country, such preparations are virtually unavailable, if not illegal. However, we should not overlook the fact here that flavonoids are absorbed from the human gut into the blood, and thus may cause similar pharmacological effects (Middleton).

Ursolic acid, oleanolic acid, chlorogenic and caffeic acids, sorbitol, fructose, harnic acid, adenine, and guanine (Bersin & Müller, Braasch & Bienroth, Nikolov & Ivanov) were isolated in the 1950s, but showed no activity on either the vessels or heart. Choline and acetylcholine were also isolated, but these are, for the most part, ubiquitous in higher plants (Sajner). According to Zeylstra (1983), the hawthorn preparations are most active when the whole plant extract is used, not an isolated fraction. Weiss, a German doctor with nearly 40 years of clinical experience with herbal remedies, says,"It is obvious that the actions of the individual elements (of hawthorn) are not merely additive or synergic, but that genuine potentiation occurs. So the role of these minor constituents may be to support the more active and unique compounds. For instance, a glyceroethanolic extract of the buds of C. laevigata has demonstrated greater cardioactivity than any individual constituent tested (Ficarra, et al., 1984b).