Hypericum perforatum

Botanical descriptionhypericum-perforatum2

Hypericum perforatum is a yellow-flowering, stoloniferous or sarmentose, perennial herb indigenous to Europe, which has been introduced to many temperate areas of the world and grows wild in many meadows. The common name comes from its traditional flowering and harvesting on St John's day, 24 June. The genus name Hypericum is derived from the Greek words hyper (above) and eikon (picture), in reference to the traditional use of the plant to ward off evil, by hanging plants over a religious icon in the house during St John's day. The species name perforatum refers to the presence of small oil glands in the leaves that look like windows, which can be seen when they are held against the light.

St John's wort is a perennial plant with extensive, creeping rhizomes. Its stems are erect, branched in the upper section, and can grow to 1 m high. It has opposing, stalkless, narrow, oblong leaves that are 12 mm long or slightly larger. The leaves are yellow-green in color, with transparent dots throughout the tissue and occasionally with a few black dots on the lower surface. Leaves exhibit obvious translucent dots when held up to the light, giving them a ‘perforated’ appearance, hence the plant's Latin name.

Its flowers measure up to 2.5 cm across, have five petals, and are colored bright yellow with conspicuous black dots. The flowers appear in broad cymes at the ends of the upper branches, between late spring and early to mid summer. The sepals are pointed, with glandular dots in the tissue. There are many stamens, which are united at the base into three bundles. The pollen grains are ellipsoidal.

When flower buds (not the flowers themselves) or seed pods are crushed, a reddish/purple liquid is produced.
Ecology

St John's wort reproduces both vegetatively and sexually. It thrives in areas with either a winter- or summer-dominant rainfall pattern; however, distribution is restricted by temperatures too low for seed germination or seedling survival. Altitudes greater than 1500 m, rainfall less than 500 mm, and a daily mean January (in Southern hemisphere) temperature greater than 24 degrees C are considered limiting thresholds. Depending on environmental and climatic conditions, and rosette age, St John's wort will alter growth form and habit to promote survival. Summer rains are particularly effective in allowing the plant to grow vegetatively, following defoliation by insects or grazing.

The seeds can persist for decades in the soil seed bank, germinating following disturbance.

Medicinal uses
Depression treatment use

St John's wort is widely known as an herbal treatment for depression. In some countries, such as Germany, it is commonly prescribed for mild depression, especially in children and adolescents. It is proposed that the mechanism of action of St. John's wort is due to the inhibition of reuptake of certain neurotransmitters.

A report from the Cochrane Review states:

    The available evidence suggests that the Hypericum extracts tested in the included trials a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; and c) have fewer side-effects than standard antidepressants.
    There are two issues that complicate the interpretation of our findings:
    1) While the influence of precision on study results in placebo-controlled trials is less pronounced in this updated version of our review compared to the previous version (Linde 2005a), results from more precise trials still show smaller effects over placebo than less precise trials.
    2) Results from German-language countries are considerably more favourable for Hypericum than trials from other countries.

In one study, St John's wort was not found to be effective for patients suffering from dysthymia, a less severe and more chronic variety of depression.However, St John's wort has been shown to be effective in the treatment of mild to moderate depression in certain studies.

Standardized extracts are generally available over the counter, though in some countries (such as the Republic of Ireland) a prescription is required. Extracts are usually in tablet or capsule form, and also in teabags and tinctures.
Other medical uses

St John's wort is being studied for effectiveness in the treatment of certain somatoform disorders. Results from the initial studies are mixed and still inconclusive; some research has found no effectiveness, other research has found a slight lightening of symptoms. Further study is needed and is being performed.

A major constituent chemical, hyperforin, may be useful for treatment of alcoholism, although dosage, safety and efficacy have not been studied.Hyperforin has also displayed antibacterial properties against gram-positive bacteria, although dosage, safety and efficacy has not been studied.Herbal medicine has also employed lipophilic extracts from St John's wort as a topical remedy for wounds, abrasions, burns, and muscle pain.The positive effects that have been observed are generally attributed to hyperforin due to its possible antibacterial and anti-inflammatory effects.For this reason hyperforin may be useful in the treatment of infected wounds and inflammatory skin diseases. In response to hyperforin's incorporation into a new bath oil, a study to assess potential skin irritation was conducted which found good skin tolerance of St John's wort.
Fruit

A randomized controlled trial of St John's wort found no significant difference between it and placebo in the management of ADHD symptoms over eight weeks. However, the St John's wort extract used in the study, originally confirmed to contain 0.3% hypericin, was allowed to degrade to levels of 0.13% hypericin and 0.14% hyperforin. Given that the level of hyperforin was not ascertained at the beginning of the study, and levels of both hyperforin and hypericin were well below that used in other studies, little can be determined based on this study alone.[19] Hypericin and pseudohypericin have shown both antiviral and antibacterial activities. It is believed that these molecules bind non-specifically to viral and cellular membranes and can result in photo-oxidation of the pathogens to kill them.[1]

A research team from the Universidad Complutense de Madrid (UCM) published a study entitled "Hypericum perforatum. Possible option against Parkinson's disease", which suggests that St John's wort has antioxidant active ingredients that could help reduce the neuronal degeneration caused by the disease.[20][21][22][23]

Recent evidence suggests that daily treatment with St John's wort may improve the most common physical and behavioural symptoms associated with premenstrual syndrome.[24]

St John's wort was found to be less effective than placebo, in a randomized, double-blind, placebo-controlled trial, for the treatment of irritable bowel syndrome.[25]

St John's wort alleviated age-related long-term memory impairment in rats.[26]
Chemical constituents

Herb and flowers contain various polyphenols: flavonoids (epigallocatechin, rutin, hyperoside, isoquercetin, quercitrin, quercetin, I3,II8-biapigenin, amentoflavone, astilbin, miquelianin[27]), phenolic acids (chlorogenic acid, 3-O-coumaroylquinic acid), and various naphtodianthrones: (hypericin, pseudohypericin, protohypericin, protopseudohypericin), phloroglucinols (hyperforin, adhyperforin). The naphthodianthrones hypericin and pseudohypericin along with the phloroglucinol derivative hyperforin are thought to be the active components.[1][28][29][30] It also contains essential oils composed mainly of sesquiterpenes.[1]Other medical uses

St John's wort is being studied for effectiveness in the treatment of certain somatoform disorders. Results from the initial studies are mixed and still inconclusive; some research has found no effectiveness, other research has found a slight lightening of symptoms. Further study is needed and is being performed.

A major constituent chemical, hyperforin, may be useful for treatment of alcoholism, although dosage, safety and efficacy have not been studied.[16][17] Hyperforin has also displayed antibacterial properties against gram-positive bacteria, although dosage, safety and efficacy has not been studied.[18] Herbal medicine has also employed lipophilic extracts from St John's wort as a topical remedy for wounds, abrasions, burns, and muscle pain.[17] The positive effects that have been observed are generally attributed to hyperforin due to its possible antibacterial and anti-inflammatory effects.[17] For this reason hyperforin may be useful in the treatment of infected wounds and inflammatory skin diseases.[17] In response to hyperforin's incorporation into a new bath oil, a study to assess potential skin irritation was conducted which found good skin tolerance of St John's wort.[17]
Fruit

A randomized controlled trial of St John's wort found no significant difference between it and placebo in the management of ADHD symptoms over eight weeks. However, the St John's wort extract used in the study, originally confirmed to contain 0.3% hypericin, was allowed to degrade to levels of 0.13% hypericin and 0.14% hyperforin. Given that the level of hyperforin was not ascertained at the beginning of the study, and levels of both hyperforin and hypericin were well below that used in other studies, little can be determined based on this study alone.[19] Hypericin and pseudohypericin have shown both antiviral and antibacterial activities. It is believed that these molecules bind non-specifically to viral and cellular membranes and can result in photo-oxidation of the pathogens to kill them.[1]

A research team from the Universidad Complutense de Madrid (UCM) published a study entitled "Hypericum perforatum. Possible option against Parkinson's disease", which suggests that St John's wort has antioxidant active ingredients that could help reduce the neuronal degeneration caused by the disease.[20][21][22][23]

Recent evidence suggests that daily treatment with St John's wort may improve the most common physical and behavioural symptoms associated with premenstrual syndrome.[24]

St John's wort was found to be less effective than placebo, in a randomized, double-blind, placebo-controlled trial, for the treatment of irritable bowel syndrome.[25]

St John's wort alleviated age-related long-term memory impairment in rats.[26]
Chemical constituents

Herb and flowers contain various polyphenols: flavonoids (epigallocatechin, rutin, hyperoside, isoquercetin, quercitrin, quercetin, I3,II8-biapigenin, amentoflavone, astilbin, miquelianin), phenolic acids (chlorogenic acid, 3-O-coumaroylquinic acid), and various naphtodianthrones: (hypericin, pseudohypericin, protohypericin, protopseudohypericin), phloroglucinols (hyperforin, adhyperforin). The naphthodianthrones hypericin and pseudohypericin along with the phloroglucinol derivative hyperforin are thought to be the active components.It also contains essential oils composed mainly of sesquiterpenes.

Pharmacokinetic interactions

St John's wort has been shown to cause multiple drug interactions through induction of the cytochrome P450 enzyme CYP3A4, but also CYP2C19. This results in the increased metabolism of those drugs, resulting in decreased concentration and clinical effect. The principal constituents thought to be responsible are hyperforin and amentoflavone.

St John's wort also has been shown to cause drug interactions through the induction of the P-glycoprotein (P-gp) efflux transporter. Increased P-gp expression results in decreased absorption and increased clearance of those drugs, which leads to lower clinical concentrations and efficacy.

Examples of drugs causing clinically significant interactions with St John's wort
Class                                                                                           Drugs
Antiretrovirals                                                      Non-nucleoside reverse transcriptase inhibitors, protease inhibitors
Benzodiazepines                                                   Alprazolam, midazolam
Hormonal contraception                                       Combined oral contraceptives
Immunosuppressants                                           Calcineurin inhibitors, cyclosporine, tacrolimus
Antiarrhythmics                                                   Amiodarone, flecainide, mexiletine
Beta-blockers                                                      Metoprolol, carvedilol
Calcium channel blockers                                    Verapamil, diltiazem, amlodipine
Statins (cholesterol-reducing medications              Lovastatin, simvastatin, atorvastatin
Others                                                                 Digoxin, methadone, omeprazole, phenobarbital, theophylline,                                                              warfarin, levodopa, buprenorphine, irinotecan

 

Reference: Rossi, 2005; Micromedex

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