View source for Biology:Hypericum perforatum

{{Short description|Flowering plant in the St John's wort family Hypericaceae}}
{{Speciesbox
| image = Saint John's wort flowers.jpg
| genus = Hypericum
| parent = Hypericum sect. Hypericum
| species = perforatum
| authority = [[Biography:Carl Linnaeus|L.]]
| subdivision_ranks = Subspecies
| subdivision = *''H. p.'' ssp. ''perforatum''
*''H. p.'' ssp. ''songaricum''{{break}}{{small|(Ledeb. ex Rchb.) N.Robson}}
*''H. p.'' ssp. ''veronense''{{break}}{{small|(Ledeb. ex Rchb.) N.Robson}}
*''H. p.'' ssp. ''chinense''{{break}}{{small|(Schrank) H.Lindb.}}
| synonyms = *''H. officinale'' {{small|Gaterau}}
*''H. officinarum'' {{small|Crantz}}
*''H. vulgare'' {{small|Lam.}}
}}'''''Hypericum perforatum''''', commonly known as '''St John's wort''', is a [[Biology:Flowering plant|flowering plant]] in the family [[Biology:Hypericaceae|Hypericaceae]]. It is a [[Biology:Perennial plant|perennial plant]] that grows up to one meter tall, with many yellow flowers that have clearly visible black glands around their edges, long [[Biology:Stamen|stamen]]s (male reproductive organs), and three [[Biology:Gynoecium|pistils]] (female reproductive organs). Probably a [[Biology:Hybrid|hybrid]] between the closely related ''[[Biology:Hypericum attenuatum|H. attenuatum]]'' and ''[[Biology:Hypericum maculatum|H. maculatum]]'' that originated in Siberia, the species is now [[Biology:Cosmopolitan distribution|found worldwide]]. It is native to temperate regions across Eurasia and North Africa, and has been introduced to East Asia, Australia, New Zealand, and parts of North and South America. In many areas where it is not native, ''H. perforatum'' is considered a [[Biology:Noxious weed|noxious weed]]. It densely covers open areas to the exclusion of native plants, and is poor [[Biology:Grazing|grazing]] material. As such, methods for [[Biology:Biological pest control|biocontrol]] have been introduced in an attempt to slow or reverse the spread of the species.

The species produces numerous [[Chemistry:Phytochemical|chemical compounds]] that are highly active. These chemicals are harmful to large animals, especially sheep, and help to deter herbivores from consuming the plant. Other chemicals in the plant, such as [[Chemistry:Hypericin|hypericin]] and [[Chemistry:Hyperforin|hyperforin]], have various uses in medicine. St John's wort has been used in [[Medicine:Traditional medicine|traditional medicine]] since at least the first century AD, often as a cure-all or [[Medicine:Panacea|panacea]]. The oil from its glands can be extracted, or its above-ground parts can be ground into a powder called herba hyperici. In modern times, its use as an [[Chemistry:Antidepressant|antidepressant]] has been the focus of numerous studies and clinical trials; however, the active ingredients can be very harmful or even lethal when taken alongside other medicines.

==Description==
''Hypericum perforatum'' is an [[Biology:Herbaceous plant|herbaceous]] [[Biology:Perennial plant|perennial plant]] with hairless ([[Biology:Leaf#glabrous|glabrous]]) stems and leaves.<ref name="WHO">{{cite book |last1=WHO |title=WHO Monographs on Selected Medicinal Plants 2: 2002 – V, 357 S.: graph. Darst |date=2002 |publisher=World Health Organization |location=Geneva, Switzerland |isbn=9241545372 |pages=149–165 |url=https://archive.org/details/medicinal-plants/who-monographs-on-selected-medicinal-plants-vol-2/page/149 |access-date=28 July 2023 |language=English}}</ref> The root of each plant is slender and woody with many small, fibrous small side roots and also extensive, creeping [[Biology:Rhizome|rhizome]]s.<ref name="Canada" /> The [[Biology:Taproot|central root]] grows to a depth of 0.6–1.5&nbsp;meters into the soil depending on conditions.<ref name="FSControl" /> The crown of the root is woody.<ref name="Canada" />

[[File:Hypericum perforatum stem cross section.jpg|thumb|left|Stem cross section]]
Its stems are erect and branched in the upper section, and usually range from 0.3 metres to 1 metre in height.<ref name="FSControl" /> The stems are woody near their base and look like they have segmented joints from the [[Biology:Leaf scar|scars]] left behind after the leaves fall off.<ref name=NorthField>{{cite book |title= North American Wildland Plants: A Field Guide |author= James L. Stubbendieck |author2=Stephan L. Hatch |author3=L. M. Landholt |edition= illustrated |publisher= University of Nebraska Press |year= 2003 |isbn= 978-0-8032-9306-9 |page= 323}}</ref> 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.<ref name="Canada">{{cite book |last1=Gillett |first1=John M. (John Montague) |title=The St. John's-Worts of Canada (Guttiferae) |date=1981 |publisher=National Museums of Canada, National Museum of Natural Sciences |location=Ottawa, Canada |isbn=978-0-660-10323-5 |pages=25–26 |url=https://archive.org/details/stjohnswortsofca0000gill/page/25 |access-date=27 July 2023}}</ref>

[[File:Hypericum-perforatum(Blatt).jpg|thumb|Leaf showing translucent glands and dark glands near the edges|224x224px]]
It has leaves that attach on [[Biology:Phyllotaxis|opposite]] sides of the stems without a stalk ([[Biology:Sessility (botany)|sessile]]). The leaves vary in shape from being very narrow and almost grass-like ([[Biology:Glossary of leaf morphology#linear|linear]]), to a rounded oval slightly wider at the base with a rounded tip or not much of a tip ([[Biology:Glossary of leaf morphology#elliptic|elliptic]]), or even narrow with the widest portion towards the end of the leaf like a reversed lance point, but still long and narrow ([[Biology:Glossary of leaf morphology#elliptic|oblanceolate]]).<ref name="Canada" /> The principle leaves range in length from 0.8 to 3.5 centimetres<ref name="WHO" /> and 0.31–1.6 centimetres in width.<ref name="Canada" /> Leaves borne on the branches subtend the shortened branchlets. The leaves are yellow-green in color, with scattered translucent dots of glandular tissue.<ref>{{cite journal |last1=Soelberg |first1=J. |last2=Jorgensen |first2=L. B. |last3=Jager |first3=A. K. |title=Hyperforin Accumulates in the Translucent Glands of Hypericum perforatum |journal=Annals of Botany |date=26 January 2007 |volume=99 |issue=6 |pages=1097–1100 |doi=10.1093/aob/mcm057|pmid=17468113 |pmc=3243575 }}</ref><ref>{{cite journal |last1=Ciccarelli |first1=D |title=Translucent Glands and Secretory Canals in Hypericum perforatum L. (Hypericaceae): Morphological, Anatomical and Histochemical Studies During the Course of Ontogenesis |journal=Annals of Botany |date=October 2001 |volume=88 |issue=4 |pages=637–644 |doi=10.1006/ANBO.2001.1514 |url=https://academic.oup.com/aob/article-pdf/88/4/637/7982078/880637.pdf |access-date=28 July 2023}}</ref> The dots are clearly visible when held up to the light, giving the leaves a [[Engineering:Perforation|perforated]] appearance.<ref>{{cite book |last1=Fritsch |first1=F. E. |last2=Salisbury |first2=E. J. |title=An Introduction to the Structure and Reproduction of Plants |date=1920 |publisher=G. Bell and Sons Ltd. |location=London |page=151 |url=https://archive.org/details/introductiontost00frituoft/page/151 |access-date=28 July 2023}}</ref> The edges (margins) of the leaves usually have scattered black dots, often called dark glands, though sometimes they will appear away from the edges.<ref name="Canada" /><ref>{{cite journal |last1=Zobayed |first1=S. M. A. |last2=Afreen |first2=F. |last3=Goto |first3=E. |last4=Kozai |first4=T. |title=Plant–Environment Interactions: Accumulation of Hypericin in Dark Glands of Hypericum perforatum |journal=Annals of Botany |date=1 October 2006 |volume=98 |issue=4 |pages=793–804 |doi=10.1093/aob/mcl169 |pmid=16891333 |pmc=2806163 }}</ref> The odor of the plant is faint, but aromatic, resembling that of resins like balsam. The taste of the plant is bitter and acrid.<ref name="WHO" />

===Flowering characteristics===
[[File:Hypericum perforatum 123.jpg|left|thumb|200x200px|Blossom showing black colored dark glands at the edges of the petals]]
The flowers are conspicuous and showy, measuring about 1.5–2.5&nbsp;cm across, and are bright yellow with black dots along the edges of the petals.<ref>{{cite web |last1=Chen |first1=Shu-Yee |last2=Hamer |first2=Deborah |title=Common St.John's Wort |url=http://www.bio.brandeis.edu/fieldbio/EFG_DEB_SHU/species%20pages/St.John's%20Wort/St.John's%20Wort.html |website=A Field Guide to Non-Native Species of Eastern Massachusetts |publisher=Brandeis University |access-date=29 July 2023 |date=2003}}</ref><ref name="Canada" /><ref name="Stace">{{cite book|last=Stace|first=C. A.|year=2010 |title=New Flora of the British Isles|url=https://archive.org/details/newflorabritishi00stac|url-access=limited|edition=Third|publisher=Cambridge University Press|location = Cambridge, U.K.| isbn=978-0-521-70772-5 |page=[https://archive.org/details/newflorabritishi00stac/page/n374 339]}}</ref> Each of the flowers normally has five large [[Biology:Petal|petal]]s and five smaller leaf-like [[Biology:Sepal|sepal]]s below them. The sepals are about 4–5&nbsp;mm in length, green in color, are shaped like the head of a spear ([[Biology:Glossary of leaf morphology#lanceolate|lanceolate]] shape) with a pointed tip, and the same clear and black glands as the leaves. The petals are significantly longer, 8–12&nbsp;mm in length, and have an oblong shape. They completely hide the sepals from the front side of the flower.<ref name="Jepson">{{cite web |title=''Hypericum perforatum'' subsp. ''perforatum'' |url=https://ucjeps.berkeley.edu/eflora/eflora_display.php?tid=91766 |website=The Jepson Herbarium |publisher=University of California, Berkeley |access-date=29 July 2023 |date=2023}}</ref> The many bright yellow [[Biology:Stamen|stamen]]s are united at the base into three bundles.<ref name="Jepson" /> The stalk portion of the stamens, the filaments, vary in length and stick out in every direction from the center of the flower.<ref name="Canada" /> The [[Biology:Pollen|pollen]] grains are pale brown to orange in color.<ref>{{Cite web |title=Hypericum perforatum |url=https://pollenatlas.net/hypericaceae/hypericum/hypericum-perforatum |access-date=2023-09-27 |website=Pollen Atlas}}</ref>

The flowers are arranged along one side of each flowering stem with two flowers at each node (a [[Biology:Inflorescence#Determinate or cymose|helicoid cyme]]) at the ends of the upper branches, between late spring and early to mid-summer.<ref name="Mehta">{{cite web |last=Mehta |first=Sweety |date=2012-12-18 |title=Pharmacognosy of St. John's Wort |url=http://pharmaxchange.info/press/2012/12/pharmacognosy-of-st-johns-wort/ |access-date=2014-02-16 |publisher=Pharmaxchange.info}}</ref> Each flowering stem bears many flowers, between 25 and 100, and also is quite leafy.<ref name="Jepson" />

The fruit of ''Hypericum perforatum'' is a capsule 7–8&nbsp;mm in length containing the seeds in three valved chambers.<ref name="Jepson" /><ref name="Canada" /> Seeds that are separated from the capsules have a much higher [[Biology:Germination|germination]] rate due to an inhibiting factor in the capsule itself.<ref name="FSControl" /> The black and lustrous seeds are rough, netted with coarse grooves.<ref name=Manual>{{cite book |title=Gray's Manual of Botany |author= Merrit Lyndon Fernald |year= 1970 |editor= R. C. Rollins |publisher= D. Van Nostrand Company |edition= Eighth (Centennial) – Illustrated|isbn= 978-0-442-22250-5 |page= 1010}}</ref> Each seed is about 1&nbsp;millimeter in size.<ref name="Jepson" /> Each plant may produce an average of 15,000 to 34,000 seeds.<ref name="FSControl" />

{{gallery|mode=packed
|Hypericum perforatum sl4.jpg|Full plant
|Hypericum perforatum plantlets.jpg|Seedlings
|7=Hypericum-perforatum-frutos.jpg|8=Fruit|9=Hypericum perforatum HC1.JPG|10=Red staining liquid from a flower bud}}

===Similar species===
''[[Biology:Hypericum maculatum|Hypericum maculatum]]'' is visually similar to ''Hypericum perforatum;'' however, its stems have four ridges instead of two and are also hollow. In addition, its leaves have fewer translucent glands and more dark glands. ''H. maculatum'' is native to the Old World but has also been introduced to North America.<ref name="FSControl" />

In North America several native species may be confused with ''Hypericum perforatum''. ''[[Biology:Hypericum anagalloides|Hypericum anagalloides]]'' is a low-growing creeping plant with rounder leaves and fewer stamens. ''[[Biology:Hypericum boreale|Hypericum boreale]]'' is a smaller plant with more delicate flowers. ''[[Biology:Hypericum canadense|Hypericum canadense]]'' has smaller flowers with sepals that show between the petals. ''[[Biology:Hypericum concinnum|Hypericum concinnum]]'' has flowers with petals that bend backward at the tip and also has much narrower, gray-green leaves. Growing in [[Earth:Riparian zone|riparian]] areas along rivers, ''Hypericum ellipticum'' has wider leaves with a more [[Biology:Glossary of leaf morphology#elliptic|elliptic]] shape. ''Hypericum scouleri'' has leaves that are broader at the base and also thicker. All except for ''H. concinnum'' grow in environments that are generally more moist than where ''H. perforatum'' is found.<ref name="FSControl" />

=== Phytochemistry ===
[[File:Hypericin2DACS.svg|thumb|Chemical structure of hypericin|151x151px]]The most common active chemicals in ''Hypericum perforatum'' are hypericin and pseudohypericin (naphthodianthrones), and hyperforin (a phloroglucinol derivative).<ref name="Mehta" /><ref>{{cite journal |vauthors=Umek A, Kreft S, Kartnig T, Heydel B |year=1999 |title=Quantitative phytochemical analyses of six hypericum species growing in slovenia |journal=Planta Med. |volume=65 |issue=4 |pages=388–90 |doi=10.1055/s-2006-960798 |pmid=17260265 |s2cid=260248637}}</ref><ref>{{cite journal |vauthors=Tatsis EC, Boeren S, Exarchou V, Troganis AN, Vervoort J, Gerothanassis IP |year=2007 |title=Identification of the major constituents of Hypericum perforatum by LC/SPE/NMR and/or LC/MS |journal=Phytochemistry |volume=68 |issue=3 |pages=383–93 |bibcode=2007PChem..68..383T |doi=10.1016/j.phytochem.2006.11.026 |pmid=17196625 |s2cid=28120366}}</ref> It also contains a host of essential oils, the bulk of which are [[Chemistry:Sesquiterpene|sesquiterpene]]s.<ref name="Mehta" /> In the wild, the concentrations of any active chemicals can vary widely among individual plants and populations.<ref>Ernst 2003, p. 65.</ref>{{hidden begin|style=border:solid 1px #aaa|title={{center|Comparison of selected chemical constituents of ''Hypericum perforatum''<ref name=HM>{{cite book |author1= Barnes, J. |author2= Anderson, L.A. |author3= Phillipson, J.D. |title= Herbal Medicines |year= 2007 |url= http://file.zums.ac.ir/ebook/366-Herbal%20Medicines,%20Third%20edition-Joanne%20Barnes%20J.%20David%20Phillipson%20Linda%20A.%20Anderson-085369623.pdf |publisher= Pharmaceutical Press |isbn=978-0-85369-623-0 |edition=3rd |location= London, UK |orig-year= 1996 |access-date=7 February 2015 |archive-url= https://web.archive.org/web/20180701140306/http://file.zums.ac.ir/ebook/366-Herbal%20Medicines,%20Third%20edition-Joanne%20Barnes%20J.%20David%20Phillipson%20Linda%20A.%20Anderson-085369623.pdf |archive-date=1 July 2018 |url-status=dead}}</ref><ref name=NS>{{cite web|title=St. John's wort|work=Natural Standard |access-date=13 December 2013 |url=http://www.naturalstandard.com/databases/herbssupplements/stjohnswort.asp |location=Cambridge, MA}}</ref>}}}}
{| class = wikitable
! Compound !! Conc.<ref name="HM" /><br /><ref name="Xeno2012">{{cite book | title = Metabolism of Drugs and Other Xenobiotics | year = 2012 | doi = 10.1002/9783527630905 | publisher = Wiley-VCH | isbn = 978-3-527-63090-5 | editor1-last = Anzenbacher | editor2-last = Zanger | editor2-first = Ulrich M. | editor1-first = Pavel | location = Weinheim, Germany }}</ref> !! log ''P'' !! [[Chemistry:Polar surface area|PSA]] !! [[Chemistry:Acid dissociation constant|pK<sub>a</sub>]] !! Formula !! [[Physics:Molecular weight|MW]] !! [[Biology:CYP1A2|CYP1A2]]<br /><ref group = Note>In brackets is the IC<sub>50</sub>/EC<sub>50</sub> value depending on whether it is an inhibitory or inductive action being exhibited, respectively.</ref> !![[Biology:CYP2C9|CYP2C9]]<br /><ref group = Note name="auto">As with last note</ref> !! [[Biology:CYP2D6|CYP2D6]]<br /><ref group = Note name="auto" /> !! [[Biology:CYP3A4|CYP3A4]]<br /><ref group = Note name="auto" /> !! [[Biology:P-glycoprotein|PGP]]<br /><ref group = Note name="auto" /> !! t<sub>1/2</sub><ref name="Xeno2012" /> (h) !! T<sub>max</sub><ref name="Xeno2012" /> (h) !! C<sub>max</sub><ref name="Xeno2012" /> (mM) !! C<sub>SS</sub><ref name="Xeno2012" /> (mM) !! Notes/Biological activity<ref group = Note>Values given in brackets are IC<sub>50</sub>/EC<sub>50</sub> depending on whether it is an inhibitory or inductive action the compound displays towards the biologic target in question. If it pertains to bacterial growth inhibition the value is MIC<sub>50</sub></ref>
|-
| colspan="17" style="text-align:center;"| <big>'''[[Chemistry:Phloroglucinol|Phloroglucinol]]s''' (2–5%)</big>
|-
| [[Chemistry:Adhyperforin|Adhyperforin]] || 0.2–1.9 || 10–13 || 71.4 || 8.51 || C<sub>36</sub>H<sub>54</sub>O<sub>4</sub> || 550.81 || ? || ? || ? || ? || ? || ? || ? || ? || ? || ?
|-
| [[Chemistry:Hyperforin|Hyperforin]] || 2–4.5 || 9.7–13 || 71.4 || 8.51 || C<sub>35</sub>H<sub>52</sub>O<sub>4</sub> || 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>
|-
| [[Chemistry:Hypericin|Hypericin]] || 0.003-3 || 7.5–10 || 156 || 6.9±0.2 ||C<sub>30</sub>H<sub>16</sub>O<sub>8</sub> || 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 || C<sub>30</sub>H<sub>16</sub>O<sub>9</sub> || 520.44 || ? || ? || ? || ? || ? || 24.8–25.4|| 3 || 1.4–16 || 0.6–10.8 || –
|-
| colspan="17" style="text-align:center;"| <big>'''[[Chemistry:Flavonoid|Flavonoid]]s''' (2–12%)</big>
|-
| [[Chemistry:Amentoflavone|Amentoflavone]]<br /> || 0.01–0.05 || 3.1–5.1 || 174 || 2.39 || C<sub>30</sub>H<sub>18</sub>O<sub>10</sub> || 538.46 || ? || – <br />(35 nM) || – (24.3 μM) || – <br />(4.8 μM) || ? || ? || ? || ? || ? || ?
|-
| [[Chemistry:Apigenin|Apigenin]] || 0.1–0.5 || 2.1±0.56 || 87 || 6.63 || C<sub>15</sub>H<sub>10</sub>O<sub>5</sub> || 270.24 || ? || ? || ? || ? || ? || ? || ? || ? || ? || ?
|-
| [[Chemistry:Catechin|Catechin]] || 2–4 || 1.8±0.85 || 110 || 8.92 || C<sub>15</sub>H<sub>14</sub>O<sub>6</sub> || 290.27 || ? || ? || ? || ? || ?|| ? || ? || ? || ? || ?

|-
| Epigallocatechin || ? || −0.5–1.5 || 131 || 8.67 || C<sub>15</sub>H<sub>14</sub>O<sub>6</sub> || 290.27 || ? || ? || ? || ? || ? || 1.7±0.4<sup>a</sup> || 1.3–1.6<sup>a</sup> || ? || ? || ?
|-
| [[Chemistry:Hyperoside|Hyperoside]] || 0.5-2 || 1.5±1.7 || 174 || 6.17 || C<sub>21</sub>H<sub>20</sub>O<sub>12</sub> || 464.38 || ? || ? || ? || ? || ? || ? || ? || ? || ? ||
|-
| [[Chemistry:Kaempferol|Kaempferol]] || ? || 2.1±0.6 || 107 || 6.44 || C<sub>15</sub>H<sub>10</sub>O<sub>6</sub> || 286.24 || ? || ? || ? || +/- || ? || ? || ? || ? || ? || ?
|-
| [[Chemistry:Luteolin|Luteolin]] || ? || 2.4±0.65 || 107 || 6.3 || C<sub>15</sub>H<sub>10</sub>O<sub>6</sub> || 286.24 || – || ? || ? || ? || ? || ? || ? || ? || ? || ?
|-
| [[Chemistry:Quercetin|Quercetin]] || 2–4 || 2.2±1.5 || 127 || 6.44 || C<sub>15</sub>H<sub>10</sub>O<sub>7</sub> || 302.24 || – <br />(7.5 μM)<br /><sup>b</sup> || – (47 μM)<br /><sup>b</sup> || – (24 μM)<br /><sup>b</sup> || – (22 μM)<br /><sup>b</sup> || – || 20–72<sup>c</sup> || 8<sup>c</sup> || ? || ? || ?
|-
| [[Chemistry:Rutin|Rutin]] || 0.3–1.6 || 1.2±2.1 || 266 || 6.43 || C<sub>27</sub>H<sub>30</sub>O<sub>16</sub> || 610.52 || ? || ? || ? || ? || ? || ? || ? || ? || ? || ?
|-
| colspan="17" style="text-align:center;"| <big>'''Phenolic acids''' (~0.1%)</big>
|-
| [[Chemistry:Caffeic acid|Caffeic acid]] || 0.1 || 1.4±0.4 || 77.8 || 3.64 || C<sub>9</sub>H<sub>8</sub>O<sub>4</sub> || 180.16 || ? || ? || ? || – || ? || ? || ? || ? || ? || ?

|-
| [[Chemistry:Chlorogenic acid|Chlorogenic acid]] || <0.1% || -0.36±0.43 || 165 || 3.33 || C<sub>16</sub>H<sub>18</sub>O<sub>9</sub> || 354.31 || 0 || 0 || 0 || 0 || ? || ? || ? || ? || ? || ?

|}

{| class=wikitable
|+ '''Acronyms and symbols'''
! Acronym/Symbol !! Meaning
|-
| MW || Molecular weight in g•mol<sup>−1</sup>.
|-
| PGP || [[Biology:P-glycoprotein|P-glycoprotein]]
|-
| t<sub>1/2</sub> || Elimination half-life in hours
|-
| T<sub>max</sub> || Time to peak plasma concentration in hours
|-
| C<sub>max</sub> || Peak plasma concentration in mM
|-
| C<sub>SS</sub> || Steady state plasma concentration in mM
|-
| <math>\log{P}</math> || [[Physics:Partition coefficient|Partition coefficient]].
|-
| PSA || [[Chemistry:Polar surface area|Polar surface area]] of the molecule in question in square angstroms (Å<sup>2</sup>). Obtained from [[Biology:PubChem|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
|-
| <sup>a</sup> || ?
|-
| <sup>b</sup> || ?
|-
| <sup>c</sup> || ?
|}
'''Notes:'''
{{Reflist|group=Note}}
{{hidden end}}

== Taxonomy ==
[[File:Pflanzen der Heimat (Tafel 20) (6099921090).jpg|thumb|1913 [[Biology:Botanical illustration|botanical illustration]] of ''H. perforatum'' by Jost Fitschen in {{lang|de|Pflanzen der Heimat}}]]
''Hypericum perforatum'' was selected to be the [[Biology:Type species|type species]] around which the genus ''Hypericum'' is based because of its wide [[Biology:Cosmopolitan distribution|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.<ref name=":0">Ernst 2003, p. 19.</ref> The current accepted placement of ''H. perforatum'' within its genus can be summarized as follows:<ref>Robson 2002, p. 62</ref>

''[[Biology:Hypericum|Hypericum]]''
: ''Hypericum'' subg. ''Hypericum''
:: ''Hypericum'' sect. ''Hypericum''
::: ''Hypericum'' subsect. ''Hypericum''
:::: ''Hypericum'' ser. ''Senanensia''
:::: ''Hypericum'' ser. ''Hypericum''
::::: ''[[Biology:Hypericum attenuatum|H. attenuatum]]''
::::: ''[[Biology:Hypericum iwate-littorale|H. iwate-littorale]]''
::::: ''[[Biology:Hypericum maculatum|H. maculatum]]''
::::: ''H. momoseanum''
::::: ''[[Biology:Hypericum perforatum|H. perforatum]]''
::::: ''H. scouleri''
::::: ''[[Biology:Hypericum tetrapterum|H. tetrapterum]]''
::::: ''H. tosaense''
::::: ''[[Biology:Hypericum triquetrifolium|H. triquetrifolium]]''
::::: ''[[Biology:Hypericum undulatum|H. undulatum]]''

=== Phylogeny ===
''Hypericum perforatum'' has a [[Biology:Ploidy|chromosome count]] of 2n = 32. The likely reason for this is that the species is a [[Biology:Hybrid|hybrid]] between the very closely related ''[[Biology:Hypericum maculatum|H. maculatum]] subsp. immaculatum'' and ''[[Biology:Hypericum attenuatum|H. attenuatum]],'' which means it inherited sets of chromosomes from both parents and is allopolyploid. The two species almost certainly hybridized within Siberia, Russia. The equation for this hybridization is:<ref name=":0" />
{{Blockquote|text=''H. maculatum'' subsp. ''immaculatum'' (16) × ''H. attenuatum'' (16)×2 = ''H. perforatum'' (32)}}[[File:Hypericum × desetangsii 112458176.jpg|thumb|''Hypericum'' × ''desetangsii'' is a hybrid between ''H. perforatum'' and ''H. maculatum''. It displays intermediate traits of the two species.]]Because of its hybrid origins, ''Hypericum perforatum'' is one of the few species within its genus that is able to further hybridize with other species, specifically those within ''H.'' ser. ''Hypericum''. The hybrids that are descended from ''H. perforatum'' can be triploid (3 sets of chromosomes) to hexaploid (6 sets), depending on the chromosome count of the second parent species and the ploidy of the specific ''H. perforatum'' [[Biology:Gamete|gamete]] that is fertilized or is fertilizing. The triploid offspring exhibit and a mix of traits from the two parents and pass them on to their offspring; the tetraploids also have a mix of traits, but often do not pass on the traits of both parents; the pentaploids are rarely distinguishable from ''H. perforatum''. Because of this, after many generations of hybridization a wide range of traits on a spectrum between the two hybridizing species can be observed in the wild.<ref name=":1">Robson 2002, p. 64.</ref>
{| class="wikitable"
|+Hybrids involving ''H. perforatum<ref name=":1" />''
!Crossed with
!Hybrid name
!Chromosome number<ref group="a">Uncertainty in chromosome number notated by "?"</ref>
|-
|''[[Biology:Hypericum elegans|H. elegans]]''
|''H. perforatum × elegans''
|2n = 32?
|-
|''[[Biology:Hypericum tetrapterum|H. tetrapterum]]''
|''''H.'' × ''medium''''
|2n = 24?
|-
|''[[Biology:Hypericum maculatum|H. maculatum]]'' [[Biology:Subspecies|ssp.]] ''maculatum''
|''H.'' × ''desetangsii'' [[Biology:Hybrid name#Forms of hybrid names|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" |{{Reflist|group=a}}
|}

=== Etymology and common names===
The [[Biology:Genus|genus]] name ''Hypericum'' is possibly derived from the [[Social:Greek language|Greek]] words {{Lang|el|hyper}} (above) and {{Lang|el|eikon}} (picture), in reference to the tradition of hanging the plant over religious [[Religion:Icon|icon]]s in the home.<ref>{{cite book |last1=Coombes |first1=Allen J. |title=The A to Z of plant names : a quick reference guide to 4000 garden plants |date=2012 |publisher=Timber Press, Inc. |isbn=978-1-60469-196-2 |location=Portland, Oregon |page=172}}</ref> The specific epithet ''perforatum'' is [[Social:Latin|Latin]] and refers to the [[Engineering:Perforation|perforated]] appearance of the plant's leaves.<ref name="Manual" />

The common name St John's wort comes from the fact that its flowers and buds were commonly harvested at the time of the Midsummer festival, which was later Christianized as St John's Feast Day on 24 June. It was believed that harvesting the flower at this time made its healing and magical powers more potent. The herb would be hung on house and stall doors on St John's Feast Day to ward off evil spirits and to safeguard against harm and sickness to people and livestock. In other traditions it was burned in bonfires for the protection of crops along with other herbs believed to be magical.<ref>{{cite book |last1=Trickey-Bapty |first1=Carolyn |url=https://archive.org/details/martyrsmiracles0000tric/page/133 |title=Martyrs and miracles |date=2001 |publisher=Testament Books |isbn=9780517164037 |location=New York |page=132 |access-date=26 July 2023}}</ref><ref name="Englishmans" /> Because of its supposed potency in warding off spirits, the plant was also known as ''fuga daemonum'' (loosely "demon-flight").<ref name="Ernst">Ernst 2003, p. 2.</ref> Many other similarly fanciful names have been used for it including ''devil's scourge'', ''Lord God's wonder plant'', and ''witch's herb''.<ref>World Health Organization, p. 149.</ref> In medieval Kent it was called ''herbe Ion'' (Ion in this case referring to "John") as recorded in the poem ''The Feate of Gardening''.<ref>{{cite book |last1=Cecil |first1=Evelyn |url=https://archive.org/details/historyofgardeni00cecil/page/71 |title=A history of Gardening in England |date=1896 |publisher=Bernard Quaritch |location=London |pages=71–72 |access-date=26 July 2023}}</ref> 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.<ref name="Englishmans">{{cite book |last1=Grigson |first1=Geoffrey |title=The Englishman's Flora |date=1960 |publisher=Phoenix House Ltd |location=London |pages=75–79 |edition=2nd |url=https://archive.org/details/englishmansflora0000geof/page/n75 |access-date=10 August 2023}}</ref> Locally in the United States, it may also be referred to as ''Tipton-weed'', ''goatweed'', or ''Klamath weed''.<ref name="NorthWestCoast">{{cite book |author=Charles Vancouver Piper |url=https://archive.org/details/cu31924001318322 |title=Flora of the Northwest Coast |author2=Rolla Kent Beattie |publisher=Press of the New era printing Company |year=1915 |page=[https://archive.org/details/cu31924001318322/page/n259 240]}}</ref><ref name="MBGarden">{{cite web |title=Hypericum perforatum |url=https://www.missouribotanicalgarden.org/PlantFinder/PlantFinderDetails.aspx?kempercode=e198 |access-date=1 August 2023 |website=Plant Finder |publisher=Missouri Botanical Garden |location=St. Louis, Missouri}}</ref>

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''.<ref name="Ernst" /><ref name="WHO" />

=== History ===
''Hypericum perforatum'' has been known and used since at least the first century. Pedanius Dioscorides, an early [[Biology:Pharmacology|pharmacologist]], referred to either it or ''H. empetrifolium'' as ''akuron''.<ref name="Ernst" /> The species was first [[Biology:Species description|formally described]] by [[Biography:Carl Linnaeus|Carl Linnaeus]] in the second tome of ''[[Biology:Species Plantarum|Species Plantarum]]'' in 1753. In it, he gave the following brief description that would serve as the foundation for all subsequent identification of the species:<ref name="Species plantarum">{{Cite book |last1=Linné |first1=Carl |url=http://dx.doi.org/10.5962/bhl.title.669 |title=Species plantarum |last2=Salvius |first2=Lars |date=1753 |publisher=Impensis Laurentii Salvii |location=Holmiae |pages=785|doi=10.5962/bhl.title.669 }}</ref>

{{Text and translation|{{Lang|la|HYPERICUM floribus trigynis, caule ancipiti, foliis obtusis pellucido-punctatis.}}|''Hypericum'' with flowers that have three pistils, [[Biology:Glossary of botanical terms#ancipital|ancipital]] stems, and obtuse leaves with pointed dots.}}

Linnaeus also noted the species' habitat in the "meadows of Europe" and gave a short account of previous mentions of the plant.<ref name="Species plantarum" />

While Linnaeus' taxonomic [[Biology:Principle of priority|priority]] for this species is not in question, there are a number of [[Biology:Synonym (taxonomy)#Botany|botanical synonyms]] that were published in the early years of formal [[Biology:Botanical nomenclature|botanical nomenclature]]. Gaterau published {{Lang|fr|Description des plantes qui croissent aux environs de Montauban}} in 1789 which described and called the species ''Hypericum officinale'', a name now considered to be [[Biology:Nomen illegitimum|illegitimate]] under the principle of priority. Likewise, the name ''Hypericum officinarum'' by Heinrich Johann Nepomuk von Crantz in 1763 also postdated Linnaeus' 1753 naming and description and is considered invalid.<ref name="POWO" />

=== Subdivision ===
[[File:Hypericum perforatum subsp. veronense Gavoi 950m 20072014.jpg|thumb|''H. perforatum'' ssp. ''veronense'']]
''Hypericum perforatum'' exhibits a great deal of variability in its appearance across its distribution. Thus, determining the exact nature of its [[Biology:Infraspecific name|infraspecific taxa]] is difficult because of the many intermediate forms that exist.<ref name=":2" />
* ''H. perforatum'' [[Biology:Subspecies|subspecies]] ''perforatum'' <small>Stjep.-Vesel.</small> is the type form of the species. It is distributed from the origin of the species in Siberia, west to central Europe, and east to northern Mongolia. The base changes as the plant grows from round to a broad wedge shape, and the seed capsule vittae are present throughout the plant's life cycle and are almost always narrow.
** ''H. perforatum'' [[Biology:Variety (botany)|variety]] ''angustifolium'' <small>DC.</small> is a variety of the species that is found in drier climates within the range of ssp. ''perforatum''. It has leaves that look more like those of ssp. ''veronense'', but they have [[Biology:Petiole (botany)|leaf stalks]]; the glands on the seed capsule are also distinct.<ref name=":2">Robson 2002, p. 88.</ref>
** ''H. perforatum'' var. ''humile'' <small>Stranski</small> can be found in parts of the southern Balkans. These plants possess smaller, more ring-shaped leaves and the seed capsules have flattish [[Biology:Vesicle (biology and chemistry)|vesicles]] on their surface. These appear to be adaptations of ssp. ''perforatum'' in response to the mountainous habitats of the region.<ref name=":3">Robson 2002, p. 89.</ref>
* ''H. perforatum'' ssp. ''songaricum'' is likely the most primitive after ssp. ''perforatum''. Previously described as a variety by [[Biography:Karl Koch (botanist)|Karl Koch]], Norman Robson elevated the taxon to subspecies in his monograph of the genus. The leaves are sessile and have a heart-shaped base that partially surrounds the stem.<ref name=":3" />
** ''H. perforatum'' var. ''gracile'' has smaller leaves and is found in western Kazakhstan, southern Russia, and southern Ukraine. In the drier areas of this range the variety exhibits a dull grey-green color on the underside of its leaves.<ref name=":3" />
* ''H. perforatum'' ssp. ''veronense'' can be found in the Caucasus, across the Middle East to Tajikistan, and along North Africa to Macaronesia. These plants have narrower leaves and display diagonal vittae on the seed capsules. Where it meets the distribution of ssp. ''perforatum'' the two subspecies hybridize regularly.<ref name=":3" />
** ''H. perforatum'' var. ''ellipticum'' retains the diagonal vittae of the subspecies but the leaves are not as narrow. The variety is distributed in areas with greater moisture such as in the mountainous areas of Turkmenistan.<ref name=":3" />
* ''H. perforatum'' ssp. ''chinense'' is found across most of China and was introduced into Japan (under the synonym ''H. foliosissimum'' <small>Koidz.</small>). Both its leaves and flowers are smaller, and the flower clusters are smaller and more crowded on the ends of longer branches.<ref name=":3" />

== Ecology ==
''H. perforatum'' is native to temperate parts of Europe and Asia, but has spread to temperate regions worldwide as an [[Earth:Invasive species|invasive]] weed.<ref name="cabi">{{cite web |author1=Ian Popay |date=22 June 2015 |title=''Hypericum perforatum'' (St John's wort) |url=https://www.cabi.org/isc/datasheet/28268 |access-date=2 December 2018 |publisher=CABI}}</ref><ref>{{cite web |title=Hypericum perforatum L. |url=http://linnaeus.nrm.se/flora/di/hyperica/hyper/hypeperv.jpg |access-date=19 August 2015}}</ref>

===Distribution===
[[File:Hypericum perforatum distribution.png|left|thumb|Country-level distribution of ''Hypericum perforatum'' based on data from the [[Organization:Royal Botanic Gardens, Kew|Royal Botanic Gardens, Kew]]]]
''Hypericum perforatum'' is thought to be native to every nation in Europe and is only absent from the far north such as north European Russia and Svalbard. It grows in parts of North Africa and is native to Morocco, Algeria, Tunisia, and Sudan.<ref name="POWO">{{cite POWO |id=433719-1 |title=''Hypericum perforatum'' L. |access-date=1 August 2023}}</ref>

In the Arabian Peninsula it only grows in parts of Saudi Arabia. It is present and native to all of the Western Asia [[Biology:Phytogeography|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.<ref name="POWO" />

In the temperate parts of Asia, ''Hypericum perforatum'' is mostly absent from Siberia with the exception of western Siberia, the Altai Region, and the warmest parts of Krasnoyarsk Krai. It has also been introduced to Irkutsk and Buryatiya. It is a native part of the flora of Central Asia, growing in all the former Soviet republics. It also is known in almost every part of the Caucasus. In China it is native to Xinjiang (western China), central China, and southern China, but not to Inner Mongolia, Manchuria, or Tibet. In the far east of Asia it has been introduced to Primorye in Russia, Korea, and Japan.<ref name="POWO" /><ref>{{cite journal |title=''Hypericum perforatum'' L. |url=https://www.gbif.org/species/3189486 |website=GBIF Secretariat |publisher=Global Biodiversity Information Facility |access-date=1 August 2023 |language=en |doi=10.15468/39omei |date=2022 |author1=Registry-Migration.Gbif.Org }}</ref>

In North America it is found in all of the continental US states except for Utah, Arizona, Florida, and Alabama. It has also been introduced to the Canadian provinces of British Columbia, Manitoba, Ontario, Quebec, and the maritime provinces besides Labrador.<ref name="USDA">{{cite usda plants|symbol=HYPE |title=Hypericum perforatum |date=1 August 2023}}</ref> It has also been introduced to Hawaii, Cuba, and Haiti.<ref name="POWO" />

In South America it is found in Argentina, Chile, Uruguay, the Juan Fernández Islands, and the more temperate parts of Brazil in the southeast. In the southern parts of Africa it has become established in South Africa, Lesotho, and Réunion. In Australia it is now found in the states of South Australia, Tasmania, Victoria, and Western Australia. It has also been introduced to both the North and South Islands of New Zealand.<ref name="POWO" />

===Habitat===
The species can be found in a variety of habitats including open woods, meadows, grasslands, [[Earth:Steppe|steppe]], riverbanks, and stony or grassy hillsides and roadsides. It prefers dry habitats or areas with strong drainage.<ref name=":2" /> The species thrives in areas with at least 760 mm of rainfall per year; however, its distribution is restricted by temperatures too low for [[Biology:Germination|seed germination]] or seedling survival: an absolute minimum of −3{{Nbsp}}°C or an annual average of 9{{Nbsp}}°C.<ref name="cabi" /> Altitudes greater than {{convert|1500|m|ft}}, rainfall less than {{convert|500|mm|in}}, and daily mean temperatures greater than {{convert|24|C|F}} are also considered limiting thresholds.<ref name="BioactiveMolecules" />

=== Reproduction ===
[[File:Bombus terrestris P1140477a.jpg|thumb|200x200px|''Bombus terrestris'' pollinating the flowers of ''Hypericum perforatum'']]
St John's wort reproduces both [[Biology:Vegetative reproduction|vegetatively]] and [[Biology:Sexual reproduction|sexually]]. Depending on environmental and climatic conditions, and the age of the plant, St John's wort will alter the way it grows to promote survival. Summer rains are particularly effective in allowing the plant to grow vegetatively, following defoliation by insects or grazing.<ref name="BioactiveMolecules">Ramawat, Kishan Gopal. ''Bioactive Molecules and Medicinal Plants''. Springer Science & Business Media, 2008. p. 152. {{ISBN|978-3-540-74603-4}}</ref> St John's wort may also produce viable [[Biology:Apomixis|seeds without fertilization]].<ref name="FSControl" /> Its seeds can persist for decades while lying dormant underground in an ecosystem's [[Biology:Soil seed bank|soil seed bank]], germinating after they are disturbed.<ref name="feis" /><ref name="cabi" />

=== Diseases ===
''H. perforatum'' is affected by [[Biology:Phytoplasma|phytoplasma]] diseases, and when infected with [[Biology:Candidatus Phytoplasma fraxini|''Candidatus'' phytoplasma fraxini]] it shows visible symptoms, including yellowing and deformities called [[Biology:Witch's broom|witch's broom]]. Its chemical profile is also altered: naphthodianthrone, [[Chemistry:Flavonoid|flavonoid]], [[Chemistry:Amentoflavone|amentoflavone]], and pseudohypericin levels are reduced; [[Chemistry:Chlorogenic acid|chlorogenic acid]] levels are increased. Additionally, phytoplasma diseases greatly reduce the essential oil yield of the plant.<ref>{{cite journal |last1=Marcone |first1=C. |last2=Bellardi |first2=M.G. |last3=Bertaccini |first3=A. |title=Phytoplasma diseases of medicinal and aromatic plants |journal=Journal of Plant Pathology |date=2016 |volume=98 |issue=3 |pages=379–404 |doi=10.4454/JPP.V98I3.060 |jstor=44280481 }}</ref>

Dieback among populations of St John's wort is also caused by fungal anthracnose, such as ''[[Biology:Glomerella cingulata|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.<ref>Ernst 2003, pp. 23, 41.</ref>

=== Herbivores ===
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. ''[[Biology:Chrysolina quadrigemina|Chrysolina quadrigemina]]'' and ''[[Biology:Chrysolina hyperici|C. hyperici]]'' are two beetle species that feed on plants from the genus ''Hypericum'', including ''H. 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.<ref name="CanadaAg">{{cite journal |last1=Harris |first1=P. |last2=Peschkin |first2=D. P. |title=Biologcal Control of St. Johns-Wort |journal=Canada Agriculture |date=1974 |volume=19 |issue=1 |pages=13–15 |url=https://archive.org/details/canadaagricultur191cana/page/13 |publisher=Canada Department of Agriculture |location=Ottawa, Canada}}</ref> Another ''Hyericum'' specialist beetle is ''[[Biology:Agrilus hyperici|Agrilus hyperici]]'', the St John's wort root borer, whose larvae feed on the roots of ''H. perforatum'' while the adults feed on the foliage.<ref>{{cite book |editor1-last=Copping |editor1-first=L.G. |title=The manual of biocontrol agents: a world compendium |date=2004 |publisher=British Crop Protection Council |location=Alton, Hampshire, United Kingdom |isbn=1-901396-35-5 |pages=270–271 |edition=Third |url=https://archive.org/details/manualofbiocontr0000unse/page/270 |access-date=2 August 2023}}</ref>

A moth, ''[[Biology:Treble-bar|Aplocera plagiata]]'', feeds heavily upon the leaves of ''H. 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.<ref name="FSControl">{{cite book |last1=Winston |first1=Rachel |last2=Randall |first2=Carol Bell |last3=Schwarzländer |first3=Mark |last4=Reardon |first4=Richard |title=Biology and Biological Control of Common St. Johnswort |date=2010 |publisher=U.S. Dept. of Agriculture, Forest Service, FHTET |location=Morgantown, West Virginia |url=https://archive.org/details/CAT31080043 |access-date=2 August 2023}}</ref> Another moth that feeds upon ''H. perforatum'' is ''[[Biology:Euspilapteryx auroguttella|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.<ref>{{cite web|url=http://www.bladmineerders.nl/minersf/lepidopteramin/euspilapteryx/auroguttella/auroguttella.htm|title=bladmineerders.nl|author=|date=|website=bladmineerders.nl|accessdate=18 January 2019|archive-url=https://web.archive.org/web/20160304204132/http://www.bladmineerders.nl/minersf/lepidopteramin/euspilapteryx/auroguttella/auroguttella.htm|archive-date=4 March 2016|url-status=dead}}</ref><ref name="Practical">{{cite book |last1=Shield |first1=Richard |title=Practical Hints Respecting Moths and Butterflies, With Notices of Their Localities : Forming a Calendar of Entomological Operations Throughout the Year, in Pursuit of Lepidoptera |date=1856 |publisher=John Van Voorst |location=London |pages=7, 42, 59, 83, 101 |url=https://archive.org/details/practicalhintsre00shie/page/7 |access-date=10 August 2023}}</ref> ''Agonopterix hypericella'' is another small (17&nbsp;mm) gray moth that exclusively feeds upon ''Hypericum''.<ref>{{cite web |title=Agonopterix hypericella (Insecta: Lepidoptera: Depressariidae) |url=http://www2.nrm.se/en/svenska_fjarilar/a/agonopterix_hypericella.html |website=Svenska Fjärilar |publisher=Naturhistoriska Riksmuseet |access-date=10 August 2023}}</ref><ref name="Practical" />

''Zeuxidiplosis giardi'', the common St. Johnswort gall [[Biology:Midge|midge]], is a small (3&nbsp;mm) fly that eats ''H. perforatum'' while developing. The larvae feed upon leaf buds, which causes the plant to form a round growth called a gall where the developing insect can feed, is protected, and [[Biology:Pupa|pupa]]tes into a mature adult.<ref name="FSControl" />

==== Toxicity ====
''Hypericum perforatum'' is [[Medicine:Toxicity|toxic]] to numerous domestic animals such as cows, sheep, and horses. When these animals come into contact with the plant, usually through grazing, they develop serious symptoms. The first signs are reddening of the skin accompanied by swelling, which is followed by [[Biology:Necrosis|necrosis]] and sloughing of the skin. Non-pigmented, white skin is most affected by the poisoning, such as the nose and ears of certain breeds of sheep.<ref name=":4">{{Cite web |title=Guide to Poisonous Plants – College of Veterinary Medicine and Biomedical Sciences – Colorado State University |url=https://poisonousplants.cvmbs.colostate.edu/Plants/Details/43 |access-date=2023-09-23 |website=poisonousplants.cvmbs.colostate.edu}}</ref> Young animals are more susceptible to ''H. 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.<ref>{{Cite book |url=https://www.nwcb.wa.gov/pdfs/Final-WSNWCB-toxic-booklet_low_res.pdf |title=Protect Your Horses and Livestock From Toxic Plants |publisher=Washington State Noxious Weed Control Board |year=2017 |pages=49}}</ref> Additionally, affected animals will become highly [[Medicine:Photosensitivity|photosensitive]], and exposure to sunlight can exacerbate their symptoms. As such, they should be moved to a dark area; administering of [[Chemistry:Antihistamine|antihistamine]]s or [[Chemistry:Anti-inflammatory|anti-inflammatory]] medicines may also help alleviate the symptoms.<ref name=":4" />

=== Invasiveness ===
[[File:Hypericum perforatum field belair park.jpg|thumb|left|''Hypericum perforatum'' in Belair National Park, South Australia]]
Although ''H. perforatum'' is grown commercially in some regions of southeast Europe, it is listed as a [[Biology:Noxious weed|noxious weed]] in more than twenty countries and has introduced populations in South and North America, India, New Zealand, Australia, and South Africa.<ref name="cabi" /><ref name="feis">{{cite web | url = http://www.invasive.org/weedcd/pdfs/feis/Hypericumperforatum.pdf | work = Fire Effects Information System | title = SPECIES: Hypericum perforatum }}</ref> In pastures, St John's wort acts as both a toxic and invasive weed. It replaces [[Earth:Native plant|native]] [[Earth:Plant community|plant communities]] and forage vegetation to the extent of making productive land nonviable or becoming an invasive species in natural [[Earth:Habitat|habitat]]s and [[Earth:Ecosystem|ecosystem]]s.<ref name="autogenerated1">{{cite web|title=St John's wort – Hypericum perforatum|url=http://www.northwestweeds.com.au/sample-page/st-johns-wort-hypericum-perforatum/|url-status=dead|archive-url=https://web.archive.org/web/20160331070345/http://www.northwestweeds.com.au/sample-page/st-johns-wort-hypericum-perforatum/|archive-date=31 March 2016|access-date=2015-10-19|website=North West Weeds}}</ref>

Effective herbicides for control of ''Hypericum perforatum'' include [[Chemistry:2,4-Dichlorophenoxyacetic acid|2,4-D]], [[Chemistry:Picloram|picloram]], [[Chemistry:Metsulfuron-methyl|metsulfuron]], and [[Chemistry:Glyphosate|glyphosate]].<ref name="FSControl" /> Insect herbivores have also been introduced as biocontrol agents in areas outside their native range. Some of the most widely used are ''[[Biology:Chrysolina quadrigemina|Chrysolina quadrigemina]]'', ''[[Biology:Chrysolina hyperici|Chrysolina hyperici]]'', ''[[Biology:Agrilus hyperici|Agrilus hyperici]]'', ''Aplocera plagiata'', and ''Zeuxidiplosis giardi''.<ref name="Harper2010">{{cite book |last1=Harper |first1=John L. |title=Population Biology of Plants |date=2010 |publisher=Blackburn Press |isbn=978-1-932846-24-9 }}{{page needed|date=September 2021}}</ref><ref name="FSControl" />

== Uses ==
=== Traditional medicine ===
[[File:Hyperici herba by Danny S. - 001.JPG|thumb|200x200px|Dried ''Hypericum perforatum'' for use as an [[Medicine:Herbal medicine|herbal drug]] called "herba hyperici"]]
Common St John's wort has been used in [[Biology:Herbalism|herbalism]] for centuries.<ref name="nccih">{{cite web |date=October 2020 |title=St. John's Wort |url=https://nccih.nih.gov/health/stjohnswort/ataglance.htm |access-date=3 September 2023 |publisher=National Center for Complementary and Integrative Health, US National Institutes of Health}}</ref> It was thought to have medical properties in [[History:Classical antiquity|classical antiquity]] and was a standard component of ancient concoctions called theriacs, from the [[Medicine:Mithridate|Mithridate]] of Aulus Cornelius Celsus' {{Lang|la|De Medicina}} ({{circa|30}} [[Common Era|CE]]) to the Venice treacle of {{Lang|nl|d'Amsterdammer Apotheek}} in 1686.<ref>{{Citation |last=Mayor |first=Adrienne |title=Chapter 11 – Mithridates of Pontus and His Universal Antidote |date=2019-01-01 |url=https://www.sciencedirect.com/science/article/pii/B9780128153390000111 |work=Toxicology in Antiquity (Second Edition) |pages=161–174 |editor-last=Wexler |editor-first=Philip |access-date=2023-09-27 |series=History of Toxicology and Environmental Health |publisher=Academic Press |doi=10.1016/b978-0-12-815339-0.00011-1 |isbn=978-0-12-815339-0}}</ref><ref>{{Citation |last1=Karamanou |first1=Marianna |title=Chapter 12 - Theriaca Magna: The Glorious Cure-All Remedy |date=2019-01-01 |url=https://www.sciencedirect.com/science/article/pii/B9780128153390000123 |work=Toxicology in Antiquity (Second Edition) |pages=175–184 |editor-last=Wexler |editor-first=Philip |access-date=2023-09-27 |series=History of Toxicology and Environmental Health |publisher=Academic Press |doi=10.1016/b978-0-12-815339-0.00012-3 |isbn=978-0-12-815339-0 |last2=Androutsos |first2=George}}</ref> 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.<ref>{{cite journal |last1=Süntar |first1=Ipek Peşin |last2=Akkol |first2=Esra Küpeli |last3=Yılmazer |first3=Demet |last4=Baykal |first4=Turhan |last5=Kırmızıbekmez |first5=Hasan |last6=Alper |first6=Murat |last7=Yeşilada |first7=Erdem |display-authors=3 |year=2010 |title=Investigations on the in vivo wound healing potential of ''Hypericum perforatum'' L. |journal=Journal of Ethnopharmacology |volume=127 |issue=2 |pages=468–77 |doi=10.1016/j.jep.2009.10.011 |pmid=19833187}}</ref> Another part of the plant that is used is the dried flower structure, which is turned into a product known as "herba hyperici" by crushing.<ref>World Health Organization, pp. 149, 151.</ref>

=== Medical research ===
==== Antidepressant ====
{{Further|Chemistry:Hyperforin}}
[[File:Hyperforin2DACS.svg|thumb|Hyperforin, a phytochemical produced by St John's wort, may be responsible for the plant's antidepressant properties.<ref>{{Cite journal |last1=Gaid |first1=Mariam |last2=Biedermann |first2=Eline |last3=Füller |first3=Jendrik |last4=Haas |first4=Paul |last5=Behrends |first5=Sönke |last6=Krull |first6=Rainer |last7=Scholl |first7=Stephan |last8=Wittstock |first8=Ute |last9=Müller-Goymann |first9=Christel |last10=Beerhues |first10=Ludger |display-authors=3 |date=2018-05-01 |title=Biotechnological production of hyperforin for pharmaceutical formulation |url=https://www.sciencedirect.com/science/article/pii/S0939641117300929 |journal=European Journal of Pharmaceutics and Biopharmaceutics |series=Innovative Processes for Bio-Pharmaceuticals and Poorly Water-Soluble API |language=en |volume=126 |pages=10–26 |doi=10.1016/j.ejpb.2017.03.024 |issn=0939-6411 |pmid=28377273 |s2cid=4701643}}</ref>|150x150px]]
Some studies and research reviews have supported the efficacy of St John's wort as a treatment for depression in humans.<ref name="nccih" /> A 2015 meta-analysis review concluded that it has superior efficacy to [[Medicine:Placebo|placebo]] in treating depression, is as effective as standard [[Chemistry:Antidepressant|antidepressant]] pharmaceuticals for treating depression, and has fewer [[Medicine:Adverse effect|adverse effect]]s than other antidepressants.<ref name="SJW and rMAO-A inhibitors – 2015">{{cite journal | vauthors = Linde K, Kriston L, Rücker G, Jamila S, Schumann I, Meissner K, Sigterman K, Schneider A | title = Efficacy and acceptability of pharmacological treatments for depressive disorders in primary care: systematic review and network meta-analysis | journal = Annals of Family Medicine | volume = 13 | issue = 1 | pages = 69–79 | date = February 2015 | pmid = 25583895 | pmc = 4291268 | doi = 10.1370/afm.1687}}</ref> The authors concluded that it is difficult to assign a place for St John's wort in the treatment of depression owing to limitations in the available evidence base, including large variations in efficacy seen in trials performed in German-speaking countries relative to other countries. A 2008 Cochrane review of 29 clinical trials concluded that it was superior to placebo in patients with major depression, as effective as standard antidepressants and had fewer side-effects.<ref name="pmid18843608">{{cite journal | vauthors = Linde K, Berner MM, Kriston L | title = St John's wort for major depression | journal = Cochrane Database Syst Rev | issue = 4 | pages = CD000448 | year = 2008 | volume = 2008 | pmid = 18843608 | doi = 10.1002/14651858.CD000448.pub3 | editor1-last = Linde | editor1-first = Klaus | pmc = 7032678 }}</ref> A 2016 review noted that use of St John's wort for mild and moderate depression was better than [[Medicine:Placebo|placebo]] for improving depression symptoms, and comparable to antidepressant medication.<ref name="pmid27589952">{{cite journal |display-authors=3 |vauthors=Apaydin EA, Maher AR, Shanman R, Booth MS, Miles JN, Sorbero ME, Hempel S |year=2016 |title=A systematic review of St. John's wort for major depressive disorder |journal=Syst Rev |volume=5 |issue=1 |pages=148 |doi=10.1186/s13643-016-0325-2 |pmc=5010734 |pmid=27589952 |doi-access=free }}</ref> A 2017 meta-analysis found that St John's wort had comparable efficacy and safety to [[Chemistry:Selective serotonin reuptake inhibitor|SSRIs]] for mild-to-moderate depression and a lower discontinuation rate.<ref>{{cite journal |last1=Ng |first1=Qin Xiang |last2=Venkatanarayanan |first2=Nandini |last3=Ho |first3=Collin Yih Xian |title=Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis |journal=Journal of Affective Disorders |date=March 2017 |volume=210 |pages=211–221 |doi=10.1016/j.jad.2016.12.048 |pmid=28064110 }}</ref> According to the United States [[Organization:National Center for Complementary and Integrative Health|National Center for Complementary and Integrative Health]], St John's wort appears to be more effective than placebo and as effective as standard antidepressant medications for mild and moderate depression, and that it is uncertain whether this is true for severe depression or for longer than 12 weeks.<ref name="nccih" />

In the United States, St John's wort is considered a dietary supplement by the [[Organization:Food and Drug Administration|FDA]], and is not regulated by the same standards as a [[Medicine:Prescription drug|prescription drug]].<ref>{{Citation |last1=Peterson |first1=Bahtya |title=St John's Wort |date=2023 |url=http://www.ncbi.nlm.nih.gov/books/NBK557465/ |work=StatPearls |access-date=2023-08-04 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32491397 |last2=Nguyen |first2=Hoang}}</ref> In China, St John's wort combined with ''[[Biology:Eleutherococcus senticosus|Eleutherococcus senticosus]]'' is sold as an antidepressant under the name {{Lang|zh|Shūgān Jiěyù Jiāonáng}} ({{Zh|c=舒肝解郁胶囊|p=|l=Liver Soothing Depression Relief Capsules}}), according to the ''Pharmacopoeia of the People's Republic of China''. The pharmacopoeia states that it is used "for mild to moderate unipolar depression".<ref>{{Cite web |date=2020 |title=舒肝解郁胶囊 – 中国药典、药品标准、法规在线查询 |trans-title=Shugan Jieyu Capsules – Chinese Pharmacopoeia, drug standards and regulations |url=https://db.ouryao.com/yd2020/view.php?id=fe8d44bfef |access-date=2022-11-26 |website=db.ouryao.com |language=Chinese}}</ref> In some European nations, the use of ''Hypericum perforatum'' for medicinal purposes is restricted because of its classification as a [[Medicine:Drug policy|drug]].<ref>{{Cite journal |last1=Nicolussi |first1=Simon |last2=Drewe |first2=Jürgen |last3=Butterweck |first3=Veronika |last4=Meyer zu Schwabedissen |first4=Henriette E. |date=2020 |title=Clinical relevance of St. John's wort drug interactions revisited |journal=British Journal of Pharmacology |language=en |volume=177 |issue=6 |pages=1212–1226 |doi=10.1111/bph.14936 |issn=0007-1188 |pmc=7056460 |pmid=31742659}}</ref>

==== Interactions and side effects ====
St John's wort can interfere (in potentially life-endangering ways) with the effects of prescription drugs.<ref name="nccih" /> Many of these interactions have been found to be caused by high hyperforin content; consumption of St John's wort products with minimal hyperforin causes fewer side effects and less interference.<ref name=":5">{{Cite journal |last1=Chrubasik-Hausmann |first1=Sigrun |last2=Vlachojannis |first2=Julia |last3=McLachlan |first3=Andrew J |date=2018-12-09 |title=Understanding drug interactions with St John's wort ( Hypericum perforatum L.): impact of hyperforin content |journal=Journal of Pharmacy and Pharmacology |language=en |volume=71 |issue=1 |pages=129–138 |doi=10.1111/jphp.12858 |pmid=29411879 |s2cid=46807341 |issn=2042-7158|doi-access=free }}</ref> However, the concentration of St John's wort's constituent chemicals (including hyperforin) can vary widely between different products,<ref name=":6">{{Cite journal |last1=Nicolussi |first1=Simon |last2=Drewe |first2=Jürgen |last3=Butterweck |first3=Veronika |last4=Meyer |first4=Henriette |date=19 November 2019 |title=Clinical relevance of St. John's wort drug interactions revisited |journal=British Journal of Pharmacology |volume=177 |issue=6|pages=1212–1226 |doi=10.1111/bph.14936 |pmid=31742659 |pmc=7056460 }}</ref> and their dosage may not be properly marked on packaging.<ref name=":5" /> In particular, St John's wort products can reduce the effectiveness of medicines like birth control pills, heart medications, HIV drugs, cancer medications, and some [[Medicine:Anticoagulant|anticoagulant]]s.<ref name="nccih" /> The most common side effects of St John's wort products are stomach pain, fatigue, and restlessness. Other more rare effects include photosensitivity and skin irritation, breakthrough bleeding when taking oral contraceptives, and decreased effectiveness of [[Chemistry:Immunosuppressive drug|immunosuppressants]] in those who have had organ transplants.<ref name=":6" />

== References ==

=== Citations ===
{{Reflist}}

=== Bibliography ===
*{{Cite book |last=Ernst |first=Edzard |url=https://books.google.com/books?id=dAmr_Ir-WL4C |title=''Hypericum'': the genus ''Hypericum'' |publisher=Taylor & Francis |year=2003 |series=Medicinal and Aromatic Plants—Industrial Profiles |volume=31 |location=London|isbn=9781420023305 }}
*{{cite book |last1=WHO |url=https://archive.org/details/medicinal-plants/who-monographs-on-selected-medicinal-plants-vol-2/page/149 |title=WHO Monographs on Selected Medicinal Plants |date=2002 |publisher=World Health Organization |isbn=9241545372 |volume=2 |location=Geneva, Switzerland |pages=149–165 |language=English |access-date=}}
*{{Cite journal |last=Robson |first=Norman |date=2002 |title=Studies in the genus ''Hypericum'' {{small|L.}} (Guttiferae) 4(2). Section 9. ''Hypericum'' sensu lato (part 2): subsection 1. ''Hypericum'' series 1. ''Hypericum''. |url=https://www.biodiversitylibrary.org/page/2277196#page/2/mode/1up |journal=Bulletin of the British Museum (Natural History) Botany |volume=32 |pages=61–123 |via=[[Social:Biodiversity Heritage Library|Biodiversity Heritage Library]]}}

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{{Taxonbar|from=Q158289}}

[[Category:Hypericum|perforatum]]
[[Category:CYP2D6 inhibitors]]
[[Category:CYP3A4 inducers]]
[[Category:Abortifacients]]
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{{Sourceattribution|Hypericum perforatum}}