St. John’s Wort: A Review
Among the many medicinal herbs used throughout the long history of Occidental culture, St. John’s wort, Hypericum perforatum L., has always been and still is of great interest. From the time of the ancient Greeks down through the Middle Ages, the plant was considered to be imbued with magical powers and was used to ward off evil and protect against disease. As a practical folk-remedy, it has been used widely to heal wounds, remedy kidney troubles, and alleviate nervous disorders, even insanity.
In the last thirty years Hypericum perforatum has undergone extensive clinical and laboratory testing. The present article reviews the plant’s botany, history of use, chemistry, pharmacology, pharmacodynamics, medical uses, and preparations.
Taxonomy and Description: St. John’s wort is a member of the genus Hypericum, of which there are 400 species worldwide. There is some disagreement as to the plant’s family, some placing Hypericum in the segregate family Hypericaceae, while others place it in the family Guttiferae. However, most researchers now think that the morphological and chemical differences of the two families are insufficient to justify separating them [1,2].
The plants are described as glabrous perennials, erect and usually woody at the base. The ovate to linear leaves are sessile, opposite, and well-supplied with translucent glandular dots. The regular flowers have five short, subequal, entire, imbricate, basally connate sepals, and five persistent-withering yellow petals. The ovary is superior, capsicular, and three-styled. Stamens are many, arranged in bundles of threes, and the flowers are profuse, arranged in branched cymes which bloom from June until September. In the absence of insect pollination, apomixis commonly occurs.
St. John’s wort should not be confused with rose of sharon (H. calycinum), a common ornamental ground-cover in the United States. Rose of sharon flowers and leaves are much larger than those of St. John’s wort (though interestingly, anti-biotic substances have been extracted from H. calycinum that are similar in activity to substances in H. perforatum .
Range and Habitat: St. John’s wort is native to Europe, West Asia, North Africa, Madeira, and the Azores and is naturalized in many parts of the world, notably North America and Australia [4,5]. The plant spreads rapidly by means of runners or from the prodigious seed production and can invade pastures, disturbed sites, dirt roads, the sides of roads and highways, and sparse woods.
In the western United States, St. John’s wort is especially prevalent in northern California and southern Oregon, hence one of its common names, “Klamath Weed”. Because of the known photosensitizing properties of the plant, which can be toxic to cows and sheep, it has been considered a pest in some places. Prior to 1949, it was estimated to inhabit 2.34 million acres of range land in northern California. For years an attempt was made to control the plant with herbicides6, but with little success.
The solution to the problem with St. John’s wort in northern California finally proved to be with biological methods of control, not pesticides. In 1946, the leaf-beetles Chrysolina quadrigemina Rossi, and to a lesser extent C. hyperici Forst, were introduced from Australia, where it had been observed that they had a voracious appetite for Hypericum. Their appetite proved to be so voracious, in fact, that by 1957 northern California’s stands of St. John’s wort were reduced to only 1% of their original number .
Ironically, however, at the time of release of the Chrysolina beetles in California, it was not known that herbalists would one day keep Hypericum populations well under control.
Etymology of Nomenclature
The name Hypericum is ancient and may have several derivations. Yperikon was first mentioned by Euryphon, a Greek doctor from 288 BC . Pliny called the ground pine Hyperikon, though also chamaepitys and corion . One common explanation for the name Hypericum is that it may derive from ereike (heather) and hyper (above) . However, although one Greek species of Hypericum looked similar to heather (though it grew taller), it seems more likely that the name derives from eikon (a figure, possibly an unwanted apparition) and hyper (above), which relates to the ancient use of St. John’s wort to exorcise evil spirits or influences , since the plant may have been placed over religious icons as a symbol of protection. Linnaeus, who described the genus, thought that Hypericum came from yper (upper) and eikon (an image) .
The common name, St. John’s wort, is obviously a reference to St. John. Its earliest use may date back to the 6th century AD when, according to Gaelic tradition, the missionary St. Columba always carried a piece of St. John’s wort because of his great regard for St. John . Some early Christian authors claimed that red spots, symbolic of the blood of St. John, appeared on leaves of Hypericum spp. on August 29, the anniversary of the saint’s beheading, while others considered that the best day to pick the plant was on June 24, the day of St. John’s feast . In the Christian tradition, St. John represents light, hence the flowers were taken as a reminder of the sun’s bounty .
History of Use
Dioscorides, the foremost herbalist of the ancient Greeks, mentions four species of Hypericum- -Uperikon, Askuron and Androsaimon, and Koris–which he recommends for sciatica, “when drunk with 2 heim of hydromel (honey-water).” He also claims that it “expels many cholerick excrement, but it must be given continuously, until they be cured, and being smeared on it is good for ambusta (burns).” H. crispum and H. barbatum, he writes, have “a diuretical facility….and of moving ye menstrua. The seed being drunk for 40 days drives away tertians and quartans (fevers occurring every 3 or 4 days, possibly malaria)” .
Theophrastus recommends H. lanuginosum, a Greek species, for external application, while Pliny says it should be taken in wine against poisonous reptiles. H. coris, another Greek species, was mentioned by Hippocrates and Pliny . Although many older authors attest that the ancients knew of Hypericum as Fuga daemonum and used it to drive away demons, none make reference to any specific writers . Dioscorides, Pliny, and Theophrastus do not mention either this name or this use of the plant, but herbalists from the 16th and 17th centuries commonly mention the name.
In the early humoral system of medicine, Galen considered Hypericum to be hot and dry, while Paracelsus wrote of the plant in the early 1500s that it could be used as an amulet against enchantments and apparitions . St. John’s wort was used in early pre-Christian religious practices in England, and it has many legends written about it . For instance, one belief was that bringing the flowers of St. John’s wort into the house on a midsummer eve would protect one from the evil eye, banish witches, etc. Another belief was that that if one slept with a piece of the plant under one’s pillow on St. John’s Eve, “the Saint would appear in a dream, give his blessing, and prevent one from dying during the following year” . The favor St. John’s wort enjoyed is well expressed in the following poem :
St. John’s wort doth charm all the witches away.
If gathered at midnight on the saint’s holy day.
And devils and witches have no power to harm
Those that do gather the plant for a charm:
Rub the lintels and post with that red juicy flower
No thunder nor tempest will then have the power
To hurt or to hinder your houses: and bind
Round your neck a charm of a similar kind.
Several noted English herbalists, reflecting the general beliefs of their time, wrote very favorably of the virtues of St. John’s wort. For instance, Gerard (ca. 1600) tells of the ointment he made of the plant as being a “most precious remedy for deepe wounds”, and adds that “there is not a better natural balsam….to cure any such wound” .
Culpeper (ca. 1650), who was fond of ascribing astrological signs to medicinal herbs, says that Hypericum “is under the celestial sign Leo, and the dominion of the Sun.” He goes on to say that “it is a singular wound herb, healing inward hurts or bruises,” and that as an ointment “it opens obstructions, dissolves swelling and closes up the lips of wounds.” Also, he claims it is good for those who “are bitten or stung by any venomous creature, and for those that cannot make water”—which use modern science confirms—and adds that the plant helps with “sciatica, the falling sickness and the palsy” .
Other early uses of Hypericum include as an oil (made by macerating the flowering tops of the plant in oil and then placing them in the sun for two or three weeks), which was “esteemed as one of the most popular and curative applications in Europe for excoriations, wounds, and bruises” . This preparation was even used by the surgeons to clean foul wounds, and was official in the first London Pharmacopeia as Oleum Hyperici .
Other popular folk-uses for St. John’s wort have included: as a decoction for gravel and ulcerations of the ureter ; for ulcerations of the kidneys, febrifuge, vermifuge, jaundice, gout, and rheumatism ; as an infusion (1 ounce of herb to 1 pint water) for chronic catarrhs of the lungs, bowels, or urinary passages; and as a warm lotion on injuries to the spinal cord, for lacerated or injured nerves, bed sores, and lock-jaw .
The native American Indians used several indigenous species of Hypericum as an abortifacient, antidiarrheal, dermatological aid, febrifuge, hemostat, snake bite remedy, and general strengthener. After St. John’s wort was introduced by European settlers, they used it as well for similar conditions [27,28].
As for the young United States, St. John’s wort was not well-known and was rarely mentioned by prominent writers on the subject of medicinal plants. One of the first references to the plant is from Griffith (1847), who says it can be used as an oil or ointment for ulcers, tumors, and as a diuretic . Even the Eclectics, medical doctors from the late 1800’s and early 1900’s who favored herbs in their practice, did not use St. John’s wort much.
Nonetheless, King, in his Dispensatory (1876), mentions its use in urinary affections, diarrhea, worms, jaundice, menorrhagia, hysteria, nervous imbalances with depression, and its usual external applications, including the use of the saturated tincture as a substitute for arnica, in bruises . In the later Felter-Lloyd revision of King’s Dispensatory, tincture of St. John’s wort, in a dose of 10–30 drops mixed with 4 ounces of water, taken in teaspoonful doses every 1–2 hours, is prescribed for spinal irritation, shocks, concussions, puncture wounds, and hysteria .
Today, modern American herbalists still use St. John’s wort for many of the same conditions for which it has been recommended throughout the ages (32,33).
The genus Hypericum has an exceedingly complex and diverse chemical makeup. H. perforatum has been most intensively studied, but there is data available on 66 other species . The compounds that have been identified from H. perforatum can be divided into several classes, which are summarized along with their pharmacological activity in Table 1.
Table 1: Summary of Constituents and Activity of Hypericum perforatum
Constituent & References Activity & References Dianthrone derivatives [35, 36, 37]
hypericin, pseudohypericin, frangula-emodin anthranol (and a mixture of the precursors, proto-hypericin & hypericodehydrodianthrone
[38, 39] photodynamic, anti-depressive (MAO inhibitor), anti-viral Flavanols [40,41]
(+)-catechin (+ polymers: condensed tannins), leucocyanidin, (-)-epicatechin (total tannin content is 6.5-15%)
 astringent, antiinflammatory, styptic, anti-viral Flavonols [43, 44, 45, 46, 47, 48, 49]
hyperoside (hyperin), quercitin, isoquercetin, rutin, methyhesperidin, iso-quercetrin, quercitrin, I-3/II- 8-biapigenin, kaempferol
[50, 51, 52, 53, 54] capillary – strengthening, anti-inflammatory, diuretic, cholagogic, dilates coronary, arteries, sedative, tumor inhibition, antitumor, antidiarrheal Xanthones 
xanthonolignoid compound (roots)
[56,57,58] generally, xanthones exhibit anti-depressant, antitubercular, choleretic, diuretic, antimicrobial, antiviral and cardiotonic activity Coumarins 
Phenolic carboxylic acids [60, 61]
caffeic acid, chlorogenic acid, gentistic acid, ferulic acid
Phloroglucinol derivatives [62, 63, 64]  hyperforin anti-bacterial (Staphylococcus aureus) Essential oil components:
(small amounts–0.05-0.3%); a-pinene, B-pinene, myrcene, limonene
 the physiological activity of mono- and sesquiterpenes are reviewed elsewhere;  H. perforatum essential oil is antifungal n-Alkanes [71, 72]
methyl-2-octane, n-nonane, methyl-2- decane, — n-undecane, all in the series C16-C29, especially nonacosane)
0.43% of total dried herb: 1-tetracosanol (9.7%), 1-hexacosanol (27.4%), 1-octacosanol (39.4%), 1-triacontanol (23.4%)
[74, 75, 76, 77, 78, 79, 80] health products including octacosanol are sold in Japanand the U.S. as "metabolic stimulants" (Japanese studies show it stimulates feeding of silkworm larvae; studies with neurological disorders (Parkinson’s, ALS, MS) show mixed results Carotenoids 
 available oxygen in xanthophylls may explain burn-healing activity Phytosterols 
- “When the compounds interact with the infecting particles shortly after in vivo administration, disease is completely prevented.”
- “Preliminary in vitro studies with pseudohypericin indicate that it can reduce the spread of HIV.”
- The total yield of hypericin and pseudohypericin from H. triquetrifolium Turra was 0.04%.
- The compounds were still effective when administered orally or i.p. within 1 day of infection.
- No serious toxic side effects were noticed after testing over 800 mice with the compounds. Administration of the compounds did not result in abnormalities in any of a wide variety of clinical tests performed on the animals.
- Hypericin shows toxicity to some human cells at very high concentrations (10 ug/ml, or lower for some cell types). Pseudohypericin is less toxic. Fortunately, the compounds show remarkable antiviral potency “after one administration of a relatively small dose of the compounds.”
- “The compounds directly inactivate the virions or interfere with assembly or shedding of assembled viral particles.”
- “The compounds can cross the blood-brain barrier” (important for HIV
One word of caution, however: although Hypericum extracts appear promising for the treatment of retroviral infections, including HIV, it must be stressed that there has been no clinical evidence of its efficacy in humans to date (for HIV infection), and several questions remained unanswered. For instance, there is no information about the concentration needed for efficacy, even if the compounds are effective in HIV infection in humans. Furthermore, if a large concentration is effective, is it close to the photosensitizing dose? Also, it must be pointed out that the total content of these two compounds in Hypericum is quite low (dried H. perforatum has been reported to contain 0.24% hypericin , consequently, a standardized extract (to hypericin content) may be the surest way to administer the plant for viral therapy.
Clearly, the potential scope of clinical application of St. John’s wort is extensive. However, if one narrows the focus down to those activities that are most mentioned, such as anti-bacterial, anti-phlogistic, diuretic, and anti-depressive, specific clinical applications become more restricted.
In modern European medicine, St. John’s wort extracts are included in many over-the-counter and prescription drugs for mild depression, and have clinical application for bed-wetting and nightmares in children. The extract is included in diuretic preparations, and the oil is taken internally by the teaspoon to help heal gastritis, gastric ulcers, and inflammatory conditions of the colon (using a retention enema) . The oil is also used extensively in burn and wound remedies, externally.
Table 2, taken from the German Health Department’s official monograph on St. John’s wort (1984), summarizes the current clinical applications of the plant [105,106].
Table 2: Clinical Indications for St. John’s wort
Herb source: flowers of Hypericum perforatum, “gathered during the time of blooming or of the dried parts above the ground, as well as their preparations, in effective dosages.”
Clinical applications: Internally: “psychovegetative disturbances, depressive states, fear and/or nervous disturbances. Oily hypericum preparations during dyspeptic disturbances.” Externally: “Oily hypericum preparations for the treatment or after treatment of sharp or abrasive wounds, myalgias (muscular pain) and first degree burns.”
Contraindications: “None known.”
Side effects: “Photosensitization is possible, especially in light skinned people.”
Interference with other drugs: “None known.”
Dosage schedule: Average daily dose recommended is 2-4 grams of the powdered herb, or 0.2-1.0 g hypericin as a powdered extract.
Method of use: “Cut or powdered plant, liquid and solid forms for oral administration. “Liquid and semi- solid forms for external use.”
Effects: Mild anti-depressant action (monoamineoxidase [MAO] inhibitor), oily preparations have antiphlogistic activity. “Diuretic activity,…direct effect on smooth musculature.”
Besides its long history of use as a medicinal plant, St. John’s wort is also known as a photosensitizing plant that can cause sickness and even death in grazing animals (when large amounts are eaten), particularly cattle, sheep, horses, and goats, but also rabbits and rats . This toxic activity of St. John’s wort was first noted in the literature by Cirillo (1787), and since then, there have been many papers published, and the effect mentioned numerous times . The plant, however, does not seem to be a major threat to livestock, because one of the first symptoms of Hypericum intoxication includes loss of appetite, which makes the absorption of the photodynamic pigment, hypericin, self-limiting .
In the case of Hypericum toxicity, the compound hypericin is absorbed from the intestine and concentrates near the skin. When the skin of the animal is exposed to sunlight, an allergic reaction takes place. Oxygen is necessary for the photodynamic hemolysis, leading to tissue damage. In the absence of sunlight, a reaction will not occur, and the compound does not show particular toxicity. [114, 115] This first type of reaction is called ‘primary photosensitization’ . Another, more serious type, is secondary photosensitization, where the liver and other internal organs can be damaged .
Cattle appear to be more sensitive to the phototoxicity of hypericin than sheep. In one test with cattle, a single dose of 1 g per kg bodyweight of dried Hypericum showed no photosensitization or changes in liver enzymes, but 3-4 g did. If humans were as sensitive to hypericin as cattle, this dose would correlate to 59 gms for a 130 lb individual. Importantly, hypericin does not seem to be accumulative. 
Although there have been a considerable number of studies published demonstrating the phototoxicity of hypericin in various animal species [119, 120], a thorough search by this writer brings to light no evidence that there has ever been a case involving human toxicity.
Some authors recommend caution when using large quantities of St. John’s wort extract for medicinal uses, particularly for people with fair skin, who should not expose themselves to strong sunlight during Hypericum therapy . Judging by the available literature, a very moderate dose, up to 4 g of the dried herb, 30 ml of the 1:5 tincture (40% EtOH), or 240 grams of the 1:5 powdered extract per day (standardized to 0.125% hypericin), should not pose a problem, if sunlight restriction is followed [122, 123], especially given the widespread use of H. perforatum extracts in Europe. One major product is recommended by the manufacturer to be taken as 40 mg tablets (1-2 tablets, 3 times a day).
Hypericin was more effectively extracted with glycol and sunflower seed oil when the moisture content of the herb was between 50 and 70%, and 2-7 times higher at 70 degree C. than at 20 degree C. The menstruum was saturated after 12 hours and 24 hours respectively, but it took 3-4 extractions to exhaust the herb . The total extraction in one hour of hypericin with ethanol was not dependent on water content of the herb. The authors conclude that ethanol is the most suited menstruum for the extraction of dried material .
Freshly air-dried herb was moistened to 70-72% moisture and extracted at 70 degree at 1:7 with sunflower seed oil. The total content of hypericin was 2.5 mg%, and extracting the marc with ethanol could increase the content to 3.32 mg% (a 25% increase).
Hypericin content of a juice of H. perforatum and a powdered extract dropped by 14% during 1 year, and the dry extract remained stable, when stored at 20 degree C. When stored at 60 degree C., the hypericin content dropped 33%, 33%, and 47% from a powdered extract, tablets, and liquid juice, respectively .
In one extensive study, up to 80% of the hypericin was destroyed by drying of the fresh plant in sunlight . For this reason, modern herbalists generally grind the fresh tops of Hypericum and immediately macerate them in olive oil or sunflower seed oil. The oil is then pressed and filtered after two weeks and should be stored in amber bottles away from heat and light. An alcoholic tincture is made in the same way, macerating the fresh, ground tops in 70% ethyl alcohol and 30% distilled water.
St. John’s wort is currently official in the pharmacopeias of Czeckoslovakia, Poland, Roumania, and Soviet Union .
Identification and Adulteration
For identification of cut and sifted material from the commercial drug market, note the two opposite ridges on the stems. These are prominent, and an important character in differentiating different Hypericum species (see Fig. 1).
Ideally, the commercial drug should consist mostly of flowering tops, but in common practice the whole above-ground plant with a considerable quantity of stem may be present. Flowers that are present should consist of 70-90% (or more) with immature capsules, otherwise the plants may have been harvested too late in the season. The hypericin content declines immediately after anthesis (flower maturity and pollination).
The leaves, when observed with a 10X hand lens, should be characterized by many punctate glands, clearly distinguishable by holding them up to a light source. The flowers will all contain fragments of the persistent dried petals, which may have red glands (appearing black) around the perimeter.
The taste (and smell) of St. John’s wort is characteristically slightly sweet, bitter, and astringent.
A commercial oil or tincture of Hypericum should be vivid, almost fluorescent red. If the preparation is pale red to pink, the hypericin content, and thus the quality of the product, is suspect.
Several methods are given in the literature for the TLC and HPLC identification of hypericin [130, 131, 132, 133, 134, 135, 136, 137, 138], and Katalin et al (1982) report on the histological examination of St. John’s wort leaves .
Since tannins play a role in the therapeutic action of St. John’s wort extracts, standardization with this fraction has been recommended (liquid extract containing 1% tannins) .
Review: An earlier review (1969) covers the history, development and photodynamic effect, chemical constituents, synthesis of hypericin, pharmacology and uses with 127 references (in German) .
- Robson, N.K.B. 1977. Bull. Br. Mus. (Nat. Hist.), Botany 5:293.
- Taskhtajan, A.L. 1980. Bot. Rev. 46: 225.
- Shakirova, K.K., et al. 1970. “Antimicrobial properties of some species of St. John’s wort cultivated in Uzbekistan,” Mikrobiol. Zh. (Kiev) 32: 494-7 (CA 74: 34570d).
- Hickey, M. & C. King. 1981. 100 Families of flowering plants, Cambridge University Press, Cambridge.
- Wichtl, M. 1986. “Hypericum perforatum L. –Das Johanniskraut”, Zeitschrift fur Phytotherapie 3: 87-90.
- Campbell, M.H., et al. 1979. “Effect of time of application of herbicides on the long-term control of St. John’s wort (Hypericum perforatum var. angustifolium),” Aust. J. Exp. Agric. Anim. Husb. 101: 746-8.
- Pickering, C. 1879. Chronological History of Plants, Little, Brown & Co., Boston.
- Jones, W.H.S. 1964. Pliny–Natural History v. VI: 8, 53. Harvard University Press, Cambridge.
- Bailey, L.H. 1930. The Standard Cyclopedia of Horticulture, Macmillan, London.
- Fernie, W.T. 1897. Herbal Simples, John Wright & Co., Bristol.
- Jaeger, E.C. 1972. A Source-Book of Biological Names and Terms. Charles C. Thomas, Springfield, IL.
- Vickery, A.R. 1981. “Traditional uses and flolklore of Hypericum in the British Iles”, Economic Botany 35: 289-295.
- Fernie, Herbal Simples.
- Gunther, R.T. 1933. The Greek Herbal of Dioscorides, Hafner Pub. Co. (1968).
- Pickering, op cit.
- Vickery, op cit.
- Alleyne, J. 1733. A New English Dispensatory, Tho. Astley, London.
- Pratt, A. 1898. The flowering plants, grasses, sedges, and ferns of Great Britain, Frederick Warne & Co., London.
- Vickery, op cit.
- Gerard, J. 1633. The Herbal. Revised and enlarged by T. Johnson, reprinted by Dover Publications, NY (1975).
- Culpeper, N. 1847. The Complete Herbal, Thomas Kelly, London.
- Fernie, op cit.
- State Historical Society of Wisconsin. 1944. Pharmacopoeia Londinensis of 1618 reproduced in facsimile, Madison.
- Hill, J. 1808. The Family Herbal, C. Brightly & T. Kinnersley, Bungay.
- Greene, T. 1824, The Universal Herbal, Caxton Press, London.
- Fernie, op cit.
- Moerman, D.E. 1986. Medicinal Plants of Native America. University of Michigan Museum of Anthropology, technical reports, number 10, Ann Arbor.
- Vogel, V. 1970. American Indian Medicine, University of Oklahoma Press, Norman.
- Griffith, R.E. 1847. Medical Botany, Lea & Blanchard, Philadelphia.
- King, J. 1876. The American Dispensatory, 10th ed., Wilstach, Baldwin & Co., Cincinnati.
- Felter, H.W. & J.U. Lloyd. 1898. King’s American Dispensatory, 18th ed., reprinted by Eclectic Medical Publications, Portland, OR.
- Lust, J. 1974. The Herb Book. Bantam, NY.
- Moore, M. 1979. Medicinal Plants of the Mountain West, Museum of New Mexico Press, Sante Fe.
- Kitanov, G.M. & K.F. Blinova. 1987. “Modern state of the chemical study of species of the genus Hypericum.” Chemistry of natural compounds 23: 151-66.
- Brockmann, H., et al. 1974. “Zur isolierung und konstitution des pseudohypericins,” Tetrahedron Lett. 23: 1991-4.
- Dorossiev, I. 1985. “Determination of flavonoids in Hypericum perforatum,” Pharmazie 40: 585-6.
- Mathis, C. & G. Ourisson. 1963. “Etude chimio-taxonomique du genre Hypericum,” Phytochemistry 2: 157-171.
- Okpanyi, S.N. & M.L. Weischer. 1987. “Experimental animal studies of the psychotropic activity of a Hypericum extract,” Arzneim.-Forsch 37: 10-13.
- Meruelo, D., et al. 1988. “Therapeutic agents with dramatic antiretroviral activity and little toxicity at effective doses: Aromatic polycyclic diones hypericin and pseudohypericin,” Proc. Ntl. Acad. Sci. 85: 5230-34.
- Kitanov, G. 1983. “Determination of the absolute configuration of ctechins isolated from Hypericum perforatum,” Farmatsiya (Sofia) 33: 19-22 (CA 99:50290j).
- Wichtl, op cit.
- Derbentseva, et al. 1972. “Effect of tannins from Hypericum perforatum on influenza viruses,” Mikrobiol. Zh. (Kiev) 34: 768-72.
- Karryev, M.O. & N.F. Komissarenko. 1980. Izv. Akad. Nauk Turkm. SSR, Ser. Biol. Nauk 1980: 52-7. (CA 93: 182809w).
- Dorossiev, I, op cit.
- Stoyanova, A., et al. 1987. “Thin-layer chromatography of extracts of Hypericum perforatum,” Farmatsiya 1: 8-13 (CA 107:205272q).
- Hoelzl, J. & E. Ostrowski. 1987. “St. John’s wort (Hypericum perforatum L.) HPLC analysis of the main components and their variability in a population,” Dtsch. Apoth. Ztg. 127: 1227-30 (CA 107:112686).
- Berghoefer, R. & J. Hoelzl. 1987. “Biflavonoids in Hypericum perforatum. Part 1. Isolation of 13,II8- biapigenin,” Planta Med. 53: 216-17.
- Koget, T.A. 1972. “Determination of the amount of quercitrin in Hypericum perforatum,” Khim. Prir. Soedin. (2): 242-3 (CA 77:45514b).
- Maksyutina, N.P. & T.A. Koget. 1971. “Polyphenols from the grass Hypericum perforatum and the preparation novoimanin,” Khim. Prir. Soedin. 7: 363-7 (CA 75:115923u).
- Holzl, J. & E. Ostrowski. [d.m.]. “Analysis of the essential compounds of Hypericum perforatum,” Planta Medica [v.m.]: 531.
- Vasil’chenko, et al. 1986. “Analgesic action of flavonoids of Rhododendron luteum Sweet, Hypericum perforatum L., Lespedeza bicolor Turoz. and L. hedysaroides (Pall.) Kitag,” Rastit. Resur. 22: 12-21 (CA 104:142140k).
- Dittmann, J., et al. 1971. “Normalizing glucose metabolism in brain tumor slices by hyperoside,” Arzneim.-Forsch. 21: 1999-2002.
- National Academy of Sciences. 1975. “Herbal Pharmacology in the People’s Republic of China,” N.A.S., Washington.
- Vasilchenko, E.A., et al. 1986. “The analgesic effect of flavonoids of Rhododendron luteum Sweet, Hypericum perforatum, Lespedeza bicolor Turoy and L. hedysaroides (Pall),” Kitaz. Rastit. Resur. 22: 12-21.
- Nielsen, M. & P. Arends. 1978. Phytochemistry 17: 2040.
- Suzuki, O., et al. 1984. Planta Med. 50: 272.
- Hostettmannn, K. & H. Wagner. 1977. Phytochemistry 16: 821.
- Denisova-Dyatlova, O.A. & V.I. Glyzin. 1982. Glyzin. Usp. Khim. 51: 1753.
- Karryev, op cit.
- Ayuga, C. & Rebuelta, M. 1986. “Comparative study of phenolic acids of Hypericum caprifolium Boiss. and Hypericum perforatum L.,” An. R. Acad. Farm. 52: 723-7 (CA 107: 74319k).
- Ollivier, B., et al. 1985. “Separation and identification of phenolic acids by high-performance liquid chromatography and ultraviolet spectroscopy. Application to Parietaria officinalis L. and to Saint-John’s-wort (Hypericum perforatum L.).” J. Pharm. Belg. 40: 173-7.
- Guevich, A.I., et al. 1971. “Hyperforin, an antibiotic from Hypericum perforatum,” Antibiotiki 16: 510-2.
- Brondz, I., et al. 1983. “The absolute configuration of hyperforin, an antibiotic from Hypericum perforatum L., based on the crystal structure determination of its p-bromobenzoate ester,” Acta Chem. Scand., Ser. A A37: 263-5 (in English).
- Gurevich, A.I., et al. 1971. “Hyperforin, an antibiotic from Hypericum perforatum,” Antibiotiki (Moscow) 16: 510-13 (CA 75:95625t).
- Negrash, A.K. & P.Ya. Pochinok. 1972. “Comparative study of chemotherapeutic and pharmacological properties of antimicrobial preparations from common St. John’s wort,” Fitonotsidy, Mater. Soveshch. 6th, Meeting date 1969, 198-200 (CA 78:66908u).
- Sticher, O. 1977. “Plant mono-, di- and sesquiterpenoids with pharmacological or therapeutical activity,” in New Natural Products and Plant Drugs with Pharmacological, Biological or Therapeutical Activity, ed. by H. Wagner & P. Wolff, Springer-Verlag, NY.
- Khosa, R.L. & N. Bhatia. 1982. “Antifungal effect of Hypericum perforatum,: J. Sci. Res. Plants Med. 3: 49-50.
- Chialva, F., et al. 1981. “Study on the composition of the essential oil from Hypericum perforatum L. and Teucrium chamaedrys L.,” Riv. Ital. EPPOS 63: 286-8 (CA 96:11497a).
- Mathis, C. & G. Ourisson. 1964. Phytochemistry 3: 133.
- Mathis, C. & G. Ourisson. 1964. “Etude chimio-taxonomique du genre Hypericum-IV,” Phytochemistry 3: 377-8.
- Brondz, I., et al. 1983. “n-Alkanes of Hypericum perforatum: a revision”, Phytochemistry 22: 295-6.
- Mathis, C. & G. Ourisson. 1964. “Etude Chimio-taxonomique du genre hypericum-III,” Phytochemistry 3: 133-141.
- Brondz, I. & T. Greibrokk. [d.m.]. “n-1-alkanols of Hypericum perforatum”, Journal of Natural Products 46: 940-1.
- Snider, S.R. 1984. “Octacosanol in Parkinsonism [letter],” Ann. Neurol. 16: 723.
- Yamashita, M, et al. 1986. “Aqeuous compositions containing octacosanol,” Japanese patent: JP 86263937, date: 861121.
- Hohnen oil co., Ltd. 1985. “Encapsulated health food supplements,” Japanese patent: JP 85149367 A2, date: 850806.
- Mori, M. 1982. “n-hexacosanol and n-octacosanol: feeding stimulants on the larvae of the silkworm, Bombyx mori,” J. of Insect Physiology 28: 969-73.
- Tandan, R. & W.G. Bradley. 1985. “Amyotrophic lateral sclerosis: part I. Clinical features, pathology, and ethical issues in management,” Ann. Neurol. (USA) 18/3: 271-80.
- Gonsette, R.E. 1982. “Treatment of multiple sclerosis,” Bull. Soc. Belge. Ophtalmol 199-200: 275-80.
- Noris, F.H., et al. 1986. “Trial of octacosanol in amyotrophic lateral sclerosis,” Neurology (USA) 36/9: 1263-64.
- Costes, C. & T. Chantal. 1967. “Carotenoid pigments of the petals of the inflorescence of St.-John’s- wort (Hypericum perforatum),” Ann. Physiol. Veg. 9: 157-77 (CA 68:66335y).
- Kitanov, op cit.
- Mathis C., & G. Ourisson. 1964. “Etude Chimio-taxonomique du genre Hypericum-V.”, Phytochemistry 3: 379.
- Prokosheva, L.I. & L.V. Shatunova. 1985. “Content of active substances in the aboveground parts of Hypericum perforatum,” Rastit. Resur. 21: 461-3.
- Gozin, A.A. & V.S. Yasnetsov. 1979. “Effect of mineral fertilizers on the content levels of biologically active substances in common St.-John’s-wort,” Depositied Doc., VINITI 1108-79, 8 pp. Avail. VINITI (CA 92:127708s).
- Razinskaite, D. 1970. “Active substances of St.-Joh’s-wort. 1. Dynamics of the level of tannins,” Liet. TSR Mokslu Akad. Darb., Ser. C (1): 47-53 (CA 73:127742f).
- Zhebeleva, T.I. 1973. “Effect of ecological conditions on the morphology and flavonoid accumulation of Hypericum perforatum,” Rast. Resur. 9: 402-4 (CA 80:12660e).
- Razinskaite, D. 1971. “Active substances of Hypericum perforatum St. John’s wort). 2. Flavonoids and dynamics of their content”, Liet. TSR Mokslu Akad. Darb., Ser. C (1): 89-100 (CA 75:72427r).
- Tsitsina, S.I. “Results of studying some medicinal plants containing flavone compounds,” Tr. Bot. Sadov, Akad. Nauk Kaz SSR 11: 111-14 (CA 73:32345q).
- Morelli, I., et al. 1983. “Selected Medicinal Plants,” FAO Plant Production and Protection Paper 53/1, Rome.
- [author missing]. 1981. “Uterotonic action of extracts from a group of medicinal plants,” Vet. Med. Nauki 18: 94-8.
- [author missing]. 1988. Fitoterapia 59: 165.
- Vander, A.J., et al. 1970. Human Physiology, McGraw-Hill Book Co., NY.
- American Medical Association. 1983. AMA Drug Evaluations, AMA, Chicago.
- Suzuki, O., et al. 1980. “Inhibition of type A and type B monoamine oxidase by isogentisin and its 3-0- glucoside,” Planta Medica 39: 19-23.
- Suzuki, et al. 1981. “Inhibition of type A and type B monoamine oxidases by naturally occurring xanthones,” Planta Medica 42: 17-21.
- Suzuki, O., et al. 1984. “Inhibition of monoamine oxidase by hypericin,” Planta Medica 50: 272-4.
- Okpanyi, Von S.N. & M.L. Weishcer. 1987. “Tierexperimentelle Untersuchungen zur psychotropen wirksamkeit eines Hypericum-extraktes,” Arzneim.-Forsch. 37: 10-13.
- Muldner, Von H. & M. Zoller. 1984. “Antidepressive wirkung eines auf den wirkstoffkomplex hypercin standardisierten hypericum-extraktes,” Arzneim.-Forsch. 34: 918.
- Negrash, A.K., op cit.
- Aizenman, B.E. 1969. “Antibiotic preparations from Hypericum perforatum,” Mikrobiol. Zh. (Kiev) 31: 128-33, (CA 70: 118006e).
- Derbentseva, N.A. & A.S. Rabinovich. 1968. “Isolation, purification, and study of some physicochemical properties of novoimanin,” in Novoimanin Ego Lech. Svoistva, 15-18, Edited by: Solov’eva, A.I., “Naukova Dumka”: Kiev, USSR.
- Gurevich, A.I., op cit.
- Saljic, J. 1975. “Ointment for the treatment of burns,” Ger. Offen. 2,406,452 (CL. A61K), 21 Aug 1975 (CA 83: 197797).
- [author missing]. 1981. “Anti-inflammatory action of a group of plant extracts,” Vet. Med. Nauki 18: 87-94.
- Proserpio, G. 1976. “Natural sunscreens: vegetable derivatives as sunscreens and tanning agents,” Cosmet. Toiletries 91: 34, 39-44, 46.
- Morelli, I., op cit.
- Meruelo, D., G. Lavie & D. Lavie. 1988. “Therapeutic agents with dramatic antiretroviral activity and little toxicity at effective doses: aromatic polycyclic diones hypericin and pseudohypericin,” Proc. Natl. Acad. Sci. 85: 5230-5234.
- Scheel, L.D. 1972. “Photosensitizing agents,” in Toxicants Occuring Naturally in Food, National Academy of Sciences, Washington.
- Weiss, R.F. 1988. Herbal Medicine, Beaconsfield Publishers Ltd, Beaconsfield, England.
- Scheel, L.D., op cit.
- Marsh, C.D. 1930. “Toxic effect of St. Johnswort (Hypericum perforatum) on cattle and sheep,” USDA Technical bulletin No. 202.
- Araya, O.S., op cit.
- Garrett, B.J., et al. 1982. “Consumption of poisonous plants (Senecio jacobaea, Symphytum officinale, Pteridium aquilinum, Hypericum perforatum) by rats: chronic toxicity, mineral metabolism, and hepatic drug-metabolizing enzymes,” Toxicology Letters 10: 183-88.
- Pace, N. & G. MacKinney. 1941. “Hypericin, the photodynamic pigment from St. John’s wort,” Journal of the Am. CHem Soc. 63: 2570-74.
- Clare, N.T. 1952. “Photosensitization in diseases of domestic animals,” Review Sweries No. 3 of the Commonwealth Bureau of Animal Health, Commonwealth Agricultural Bureaux, Bucks, England.
- James, L.F. & A.E. Johnson. 1976. “Some major plant toxicities of the western United States,” J. of Range Manag. 29: 356-63.
- Araya, O.S., op cit.
- Zaichikova, S.G., et al. 1985. “Study of the healing properties and determination of the upper parameters of toxicity of Hypericum,” Farmatsiya 1: 62.
- Roth, L., et al. 1984. Giftpflanzen–Pflanzengifte, ecomed, Munich.
- Weiss, R.F., op cit.
- Merck 1907 Index. Merck & Co., Rahway, NJ.
- Todd, R.G. 1967. Martindale’s Extra Pharmacopoeia, The Pharmaceutical Press, London.
- Georgiev, E., et al. 1985. Effect of solvent and moisture of St. John’s wort on extraction of some biologically active substances. II. Extraction of hypericin with glycol,” Nauchni Tr. – Vissh Inst. Khranit. Vkusova Prom-st., Plovdiv 32: 257-63 (CA 105:29872h).
- Georgiev, E., et al. 1985. “Effect of solvent and moisture of St. John’s Wort on extraction of some biologically active substances. I. Extraction of hypericin with glycerides and ethyl alcohol,” Nauchni Tr. Vissh Inst. Khranit. Vkusova Promst., Plovdiv 32: 251-6 (CA 105:29871g).
- Georgiev, E., et al. 1983. “Extraction of Hypericum perforatum L.,” Nauchni Tr. – Vissh Inst. Khranit. Vkusova Prom-st., Plovdiv 30: 175-83 (CA 101: 197996n).
- Adamski, R. & E. Styp-Rekowska. 1971. “Stability of hypericin in juice, dry extract, and tablets from Hypericum perforatum plants,” Farm. Pol. 27: 237-41 (CA 75:91286k).
- Araya, O.S. & E.J.H. Ford. 1981. “An investigation of the type of photosensitization caused by the ingestion of St. John’s wort (Hypericum perforatum) by calves,” J. COmp. Path. 91: 135-41.
- Todd, R.G. (ed.). 1977. Martindale’s Extra Pharmacopoeia, The Pharmaceutical Press, London.
- Hoelzl, op cit.
- Dorosiev, I. 1985. “Determination of flavonoids in Hypericum perforatum,” Pharmazie 40: 585-6 (in English).
- Ollivier, op cit.
- Pachaly, P. 1984. “Thin layer chromatography in the pharmacy: Practical examples,” Dtsch. Apoth. Ztg. 124: 2153-61.
- Freytag, W.E. 1984. “Determination of hypericin and pseudohypericin in Hypericum perforatum L. with HPLC,” Dtsch. Apoth. Ztg 124: 2383-6.
- Vanhaelen, M. & R. Vanhaelen-Fastre. 1983. “Quantitative determination of biologically active constituents in medicinal plant crude extracts by thin-layer chromatography-densitometry. I. …..Hypericum perforatum…Silybum marianum..(and others),” J. Chromatogr. 281: 263-71 (in English).
- Chialva, F. , et al. 1983. “Direct headspace gas chromatographic analysis with glass capillary columns in quality control of aromatic herbs,” J. Chromatogr. 279: 333-40 (in English).
- Holzl, J. & E. Ostrowski, op cit.
- Steinbach, R.A. 1981. “Problems in the purification and standardization of plant drugs, for example, Hypericum,” Z. Angew. Phytother. 2:221-4 (CA 98: 113563c)
- Katalin, L., et al. 1982. “Ultrastructural Examination of leaf differentiation in St. John’s wort”, Herba Hung. 21: 21-37.
- Azaryan, R.A. 1985. “Standardization of [quality indexes for the medicinal] herb Hypericum perforatum,” Farmatsiya (Moscow) 34: 18-21 (CA 104: 56271x).
- Schilling, W. 1969. “A Review…..,” Praep. Pharm. 5: 125-34.