Hypericum perforatum

Hypericum perforatum, commonly known as St. John's wort (sometimes perforate St. John's wort or common St. John's wort), is a flowering plant in the family Hypericaceae. It is a hairless, perennial herb with woody roots, yellow flowers marked by black glands, and leaves that appear perforated due to translucent glands, producing thousands of seeds per plant.

H. perforatum is the type species of its genus, known for its historical use in folklore and traditional medicine. Probably a hybrid between the closely related H. attenuatum and H. maculatum (imperforate St. John's wort) that originated in Siberia, the species has spread worldwide. It can further hybridize with related species due to its allopolyploid nature. It is native to much of Europe, West and Central Asia, and parts of Africa and China and has been widely introduced elsewhere, thriving in well-drained, temperate habitats such as meadows, hillsides, and open woods with moderate rainfall and mild temperatures. It is a resilient, toxic, and invasive plant that reproduces sexually and vegetatively, supports specialized insect herbivores, suffers from plant diseases, and poses ecological and agricultural threats in many parts of the world.

H. perforatum has been used for centuries in traditional medicine, especially for treating wounds and depression. To prepare it for use, the oil from its glands can be extracted or its above-ground parts can be dried and ground into a powder called herba hyperici. H. perforatum exhibits antidepressant effects comparable to drugs with fewer side effects for mild to moderate depression (for which it is approved in the European Union); however, it may interact with various medications by accelerating their metabolism.

Description

thumb|Leaf showing translucent glands and dark glands near the edges

Hypericum perforatum is an herbaceous perennial plant with hairless (glabrous) stems and leaves. The root of each plant is slender and woody with many small, fibrous small side roots and also extensive, creeping rhizomes. The stems of H. perforatum are rusty-yellow to rosy in color with two distinct edges and usually have bark that sheds near the base. The stems persist through the winter and sprout new growth with flower buds in the following year; first year growth does not produce flowers.

It has leaves that attach on opposite sides of the stems without a stalk (sessile). The leaves vary in shape from being very narrow and almost grass-like (linear), to a rounded oval slightly wider at the base with a rounded tip or not much of a tip (elliptic), or even narrow with the widest portion towards the end of the leaf like a reversed lance point, but still long and narrow (oblanceolate). The dots are clearly visible when held up to the light, giving the leaves a perforated appearance. The edges (margins) of the leaves usually have scattered black dots, often called dark glands, though sometimes they will appear away from the edges. The odor of the plant is faint, but aromatic, resembling that of resins like balsam. The taste of the plant is bitter and acrid. Each of the flowers normally has five large petals and five smaller leaf-like sepals below them. The sepals are about in length, green in color, are shaped like the head of a spear (lanceolate shape) with a pointed tip, and the same clear and black glands as the leaves. The petals are significantly longer, in length, and have an oblong shape. They completely hide the sepals from the front side of the flower. The many bright yellow stamens are united at the base into three bundles. Each flowering stem bears many flowers, between 25 and 100, and also is quite leafy. Each seed is about in size. The species contains a host of essential oils, the bulk of which are sesquiterpenes. In the wild, the concentrations of any active chemicals can vary widely among individual plants and populations.

{| class = wikitable

! Compound !! Conc. !! log P !! PSA !! pK_a !! Formula !! MW !! CYP1A2<br /> !!CYP2C9<br /> !! CYP2D6<br />

|-

| colspan="17" style="text-align:center;"| <big>Phloroglucinols (2–5%)</big>

|-

| Adhyperforin || 0.2–1.9 || 10–13 || 71.4 || 8.51 || C₃₆H₅₄O₄ || 550.81 || ? || ? || ? || ? || ? || ? || ? || ? || ? || ?

|-

| Hyperforin || 2–4.5 || 9.7–13 || 71.4 || 8.51 || C₃₅H₅₂O₄ || 536.78 || + || ± || – || + || + || 3.5–16 || 2.5–4.4 || 15-235 || 53.7 || –

|-

| colspan="17" style="text-align:center;"| <big>Naphthodianthrones (0.03-3%)</big>

|-

| Hypericin || 0.003-3 || 7.5–10 || 156 || 6.9±0.2 ||C₃₀H₁₆O₈ || 504.44 || 0 || – <br />(3.4 μM) || – (8.5 μM) || – <br />(8.7 μM) || ? || 2.5–6.5 || 6–48 || 0.66-46 || ? || ?

|-

| Pseudohypericin || 0.2–0.23 || 6.7±1.8 || 176 || 7.16 || C₃₀H₁₆O₉ || 520.44 || ? || ? || ? || ? || ? || 24.8–25.4|| 3 || 1.4–16 || 0.6–10.8 || –

|-

| colspan="17" style="text-align:center;"| <big>Flavonoids (2–12%)</big>

|-

| Amentoflavone<br /> || 0.01–0.05 || 3.1–5.1 || 174 || 2.39 || C₃₀H₁₈O₁₀ || 538.46 || ? || – <br />(35 nM) || – (24.3 μM) || – <br />(4.8 μM) || ? || ? || ? || ? || ? || ?

|-

| Apigenin || 0.1–0.5 || 2.1±0.56 || 87 || 6.63 || C₁₅H₁₀O₅ || 270.24 || ? || ? || ? || ? || ? || ? || ? || ? || ? || ?

|-

| Catechin || 2–4 || 1.8±0.85 || 110 || 8.92 || C₁₅H₁₄O₆ || 290.27 || ? || ? || ? || ? || ?|| ? || ? || ? || ? || ?

|-

| Epigallocatechin || ? || −0.5–1.5 || 131 || 8.67 || C₁₅H₁₄O₆ || 290.27 || ? || ? || ? || ? || ? || 1.7±0.4^a || 1.3–1.6^a || ? || ? || ?

|-

| Hyperoside || 0.5-2 || 1.5±1.7 || 174 || 6.17 || C₂₁H₂₀O₁₂ || 464.38 || ? || ? || ? || ? || ? || ? || ? || ? || ? ||

|-

| Kaempferol || ? || 2.1±0.6 || 107 || 6.44 || C₁₅H₁₀O₆ || 286.24 || ? || ? || ? || ± || ? || ? || ? || ? || ? || ?

|-

| Luteolin || ? || 2.4±0.65 || 107 || 6.3 || C₁₅H₁₀O₆ || 286.24 || – || ? || ? || ? || ? || ? || ? || ? || ? || ?

|-

| Quercetin || 2–4 || 2.2±1.5 || 127 || 6.44 || C₁₅H₁₀O₇ || 302.24 || – <br />(7.5 μM)<br />^b || – (47 μM)<br />^b || – (24 μM)<br />^b || – (22 μM)<br />^b || – || 20–72^c || 8^c || ? || ? || ?

|-

| Rutin || 0.3–1.6 || 1.2±2.1 || 266 || 6.43 || C₂₇H₃₀O₁₆ || 610.52 || ? || ? || ? || ? || ? || ? || ? || ? || ? || ?

|-

| colspan="17" style="text-align:center;"| <big>Phenolic acids (~0.1%)</big>

|-

| Caffeic acid || 0.1 || 1.4±0.4 || 77.8 || 3.64 || C₉H₈O₄ || 180.16 || ? || ? || ? || – || ? || ? || ? || ? || ? || ?

|-

| Chlorogenic acid || <0.1% || -0.36±0.43 || 165 || 3.33 || C₁₆H₁₈O₉ || 354.31 || 0 || 0 || 0 || 0 || ? || ? || ? || ? || ? || ?

|}

{| class=wikitable

|+ Acronyms and symbols

! Acronym/Symbol !! Meaning

|-

| MW || Molecular weight in g•mol⁻¹.

|-

| PGP || P-glycoprotein

|-

| t_1/2 || Elimination half-life in hours

|-

| T_max || Time to peak plasma concentration in hours

|-

| C_max || Peak plasma concentration in mM

|-

| C_SS || Steady state plasma concentration in mM

|-

| <math>\log{P}</math> || Partition coefficient.

|-

| PSA || Polar surface area of the molecule in question in square angstroms (Ų). Obtained from PubChem

|-

| Conc. || These values pertain to the approximation concentration (in %) of the constituents in the fresh plant material

|-

| – || Indicates inhibition of the enzyme in question.

|-

| + || Indicates an inductive effect on the enzyme in question.

|-

| 0 || No effect on the enzyme in question.

|-

| 5-HT || 5-hydroxytryptamine – synonym for serotonin.

|-

| DA || Dopamine

|-

| NE || Norepinephrine

|-

| GABA || γ-aminobutyric acid

|-

| Glu || Glutamate

|-

| Gly || Glycine

|-

| Ch || Choline

|-

| ^a || ?

|-

| ^b || ?

|-

| ^c || ?

|}

Notes:

Taxonomy

thumb|1913 [[botanical illustration of H.&nbsp;perforatum by Jost Fitschen in ]]

Hypericum perforatum was selected to be the type species around which the genus Hypericum is based because of its wide cosmopolitan distribution; it is the most common species of the genus in many of the areas it is found, and is one of the most widely known plants among the St John's worts in folklore and medicine.

{| class="wikitable"

|+Hybrids involving H. perforatum

|-

|H. elegans

|H. perforatum × elegans

|2n = 32?

|-

|H. tetrapterum

|'H. × medium'

|2n = 24?

|-

|H. maculatum ssp. maculatum

|H. × desetangsii nssp. carinthiacum

|2n = 24/40

|-

|H. maculatum ssp. immaculatum

|H. × desetangsii nssp. balcanicum

|2n = 24/40?

|-

|H. maculatum ssp. obtusiusculum

|H. × desetangsii nssp. desetangsii

|2n = 40

|-

| colspan="3" |

|}

Etymology and common names

The genus name Hypericum is possibly derived from the Greek words (above) and (picture), in reference to the tradition of hanging the plant over religious icons in the home. The specific epithet perforatum is Latin and refers to the perforated appearance of the plant's leaves. Many other similarly fanciful names have been used for it including devil's scourge, Lord God's wonder plant, and witch's herb. In medieval Kent it was called herbe Ion (Ion in this case referring to "John") as recorded in the poem The Feate of Gardening. Other local names for Hypericum perforatum include balm of the warrior's wound in Somerset, penny John in Norfolk, rosin rose in Yorkshire, and touch-and-heal in Northern Ireland. Locally in the United States, it may also be referred to as Tipton-weed, goatweed, or Klamath weed.

In the 21st century, any species of the genus Hypericum can be referred to as St John's wort. Therefore, it is more accurate to call Hypericum perforatum the common St John's wort or perforate St John's wort.

Linnaeus also noted the species' habitat in the "meadows of Europe" and gave a short account of previous mentions of the plant.

In the Arabian Peninsula it only grows in parts of Saudi Arabia. It is present and native to all of the Western Asia phytogeographic region from the Aegean Islands and Turkey to Israel and Palestine in the west to Afghanistan in the east, only being absent from the Sinai Peninsula. Just to the east of this area it is also native to Pakistan and the western Himalaya region of India.

In North America, it is found in all of the continental US states except for Utah, Arizona, Florida, and Alabama. It has been introduced throughout much of Canada, as well as in Hawaii, Cuba, and Haiti. Altitudes greater than , rainfall less than , and daily mean temperatures greater than are also considered limiting thresholds. St John's wort may also produce viable seeds without fertilization.

Dieback among populations of St John's wort is also caused by fungal anthracnose, such as Colletotrichum gloeosporioides. This fungus causes the stems to lose their bark (girdling) and turn brown, and dries the aboveground parts of the plant. The infection often kills the plant within the first year of its growth, or reduces productivity over a three-year deterioration.

Role as a herbivore food source

Though Hypericum perforatum is generally avoided by mammalian herbivores, a number of insects are dependent on it and its close relatives as a food source. Chrysolina quadrigemina and C. hyperici are two beetle species that feed on plants from the genus Hypericum, including H.&nbsp;perforatum. Chrysolina quadrigemina can be colored metallic blue, purple, green, or bronze and is better adapted to warm and dry climates; Chrysolina hyperici is consistently smaller, metallic green, and tends to live in areas with wetter and cooler conditions. Another Hyericum specialist beetle is Agrilus hyperici, the St John's wort root borer, whose larvae feed on the roots of H.&nbsp;perforatum while the adults feed on the foliage.

A moth, Aplocera plagiata, feeds heavily upon the leaves of H.&nbsp;perforatum as a caterpillar and is commonly known as the common St John's wort inchworm. As adults, they are a small moth with gray wings and dark gray bands. Another moth that feeds upon H.&nbsp;perforatum is Euspilapteryx auroguttella. Their caterpillars start by mining the inside of the leaves and later roll the leaves into cigar shapes to feed in greater safety. Agonopterix hypericella is another small () gray moth that exclusively feeds upon Hypericum. Young animals are more susceptible to H.&nbsp;perforatum poisoning, and the plant is most toxic in spring (when it is the most palatable to herbivores) and retains its toxic effects when dried in hay. Additionally, affected animals will become highly photosensitive, and exposure to sunlight can exacerbate their symptoms. As such, they should be moved to a dark area; administering of antihistamines or anti-inflammatory medicines may also help alleviate the symptoms. In pastures, St John's wort acts as both a toxic and invasive weed. It replaces native plant communities and forage vegetation to the extent of making productive land nonviable or becoming an invasive species in natural habitats and ecosystems.

Effective herbicides for control of Hypericum perforatum include 2,4-D, picloram, metsulfuron, and glyphosate.

Uses

thumb|Dried Hypericum perforatum for use as the [[Herbal medicine|herbal drug herba hyperici]]

Antidepressant effects

H. perforatum has approval in the European Union as a herbal product for the treatment of mild to moderate depressive episodes (according to ICD-10) and for the short-term treatment of symptoms in mild depression. It is more effective than placebo and as effective as standard antidepressants, including SSRIs, for mild to moderate depression, with some evidence suggesting fewer adverse effects and lower discontinuation rates. In America, H. perforatum is not approved as a treatment for depression, and its use in treating depression is discouraged by NIH and Cleveland Clinic. H. perforatum can cause serious side effects such as serotonin syndrome if taken with other antidepressants.

In vitro, it acts mainly as a reuptake inhibitor of serotonin, dopamine, and norepinephrine; additional antidepressant effects may come from its interactions with GABA receptors.

In traditional medicine

Common St. John's wort has been used in herbalism for centuries. It was used in classical antiquity and was a standard component of ancient concoctions called theriacs, from the Mithridate of Aulus Cornelius Celsus' ( CE) to the Venice treacle of in 1686. One folk use included the oily extract known as St John's oil, a red, oily liquid extracted from H.&nbsp;perforatum that may have been a treatment for wounds by the Knights Hospitaller, the Order of St John. The dried flower is crushed to make the compound known as herba hyperici.

thumb|175px|Samples of wool [[Dyeing|dyed using H.&nbsp;perforatum]]

As a dyeing pigment

H. perforatum generally produces a variety of yellows suitable for dyeing. When the pigments are extracted using ethanol, a violet-red colour is made which can be used to dye silk and wool when rinsed in vinegar. The colours produced are season-dependent.

The flowers produce a series of four different shades on wool, if used in the correct sequence. Wool mordanted with alum and unmordanted wool is used. The flowers are simmered to produce a deep red liquid dye. The alum-mordanted wool skein is added and simmered until green is made. If unmordanted wool is added to the same dye, it will turn reddish-maroon. The final colour produced is by continuing the method, to produce yellow or gold.

Inability to treat cancer

There is no clinical evidence that St John's wort is effective to treat cancer. The National Cancer Institute has commented that "the FDA has not approved the use of St. John's wort as a treatment for cancer or any other medical condition". St John's wort may reduce the efficacy of chemotherapy. However, the concentration of St John's wort's constituent chemicals (including hyperforin) can vary widely between different products, and their dosage may not be properly marked on packaging.