Hypericum perforatum

{{Short description|Flowering plant in the St John's wort family}} {{Redirect|St John's wort}} {{cs1 config|name-list-style=vanc|display-authors=3}} {{good article}} {{Use dmy dates|date=February 2020}} {{Speciesbox | image = (MHNT)_Hypericum_perforatum_flower_and_buttons.jpg | genus = Hypericum | parent = Hypericum sect. Hypericum | species = perforatum | authority = 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''' (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.<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 rhizomes.<ref name="Canada" /> The central root grows to a depth of {{convert|0.6|–|1.5|m}} into the soil depending on conditions.<ref name="FSControl" /> The crown of the root is woody.<ref name="Canada" />

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 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.&nbsp;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=}}</ref>

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).<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 |bibcode=2001AnBot..88..637C |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 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=}}</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=== thumb|Blossom showing black colored dark glands at the edges of the petals The flowers are conspicuous and showy, measuring about {{convert|1.5|–|2.5|cm|abbr=on}} across, and are bright yellow with black dots along the edges of the petals.<ref name="Canada" /><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%27s%20Wort/St.John%27s%20Wort.html |website=A Field Guide to Non-Native Species of Eastern Massachusetts |publisher=Brandeis University |access-date=29 July 2023 |date=2003 |archive-date=6 September 2023 |archive-url=https://web.archive.org/web/20230906042733/http://www.bio.brandeis.edu/fieldbio/EFG_DEB_SHU/species%20pages/St.John%27s%20Wort/St.John%27s%20Wort.html |url-status=dead }}</ref><ref name="Stace">{{cite book|last=Stace|first=C. A.|author-link = Stace, 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 petals and five smaller leaf-like sepals below them. The sepals are about {{convert|4|–|5|mm|abbr=on}} 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, {{convert|8|–|12|mm|abbr=on}} 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 stamens 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 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> 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 {{convert|7|–|8|mm|abbr=on}} 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 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 {{convert|1|mm|abbr=on}} 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=== ''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.&nbsp;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''. ''Hypericum anagalloides'' is a low-growing creeping plant with rounder leaves and fewer stamens. ''Hypericum boreale'' is a smaller plant with more delicate flowers. ''Hypericum canadense'' has smaller flowers with sepals that show between the petals. ''Hypericum concinnum'' has flowers with petals that bend backward at the tip and also has much narrower, gray-green leaves. Growing in riparian areas along rivers, ''Hypericum ellipticum'' has wider leaves with a more elliptic shape. ''Hypericum scouleri'' has leaves that are broader at the base and also thicker. All except for ''H.&nbsp;concinnum'' grow in environments that are generally more moist than where ''H.&nbsp;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>{{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 |bibcode=1999PlMed..65..388U |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> The species contains a host of essential oils, the bulk of which are sesquiterpenes.<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> In the wild, the concentrations of any active chemicals can vary widely among individual plants and populations.<ref name=Ernst-2003>{{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 }} {{hidden begin|style=border:solid 1px #aaa|title={{center|Comparison of selected chemical constituents of ''Hypericum perforatum''}}}}{{Hidden end}}</ref><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 }}{{Dead link|date=January 2026 |bot=InternetArchiveBot }}</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'' !! PSA !! pK_a !! Formula !! MW !! CYP1A2<br /><ref group = Note>In brackets is the IC₅₀/EC₅₀ value depending on whether it is an inhibitory or inductive action being exhibited, respectively.</ref> !!CYP2C9<br /><ref group = Note name="auto">As with last note</ref> !! CYP2D6<br /><ref group = Note name="auto" /> !! CYP3A4<br /><ref group = Note name="auto" /> !! PGP<br /><ref group = Note name="auto" /> !! t_1/2<ref name="Xeno2012" /> (h) !! T_max<ref name="Xeno2012" /> (h) !! C_max<ref name="Xeno2012" /> (mM) !! C_SS<ref name="Xeno2012" /> (mM) !! Notes/Biological activity<ref group = Note>Values given in brackets are IC₅₀/EC₅₀ 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 MIC₅₀</ref> |- | 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:''' {{Reflist|group=Note}}

== Taxonomy == [[File:Pflanzen der Heimat (Tafel 20) (6099921090).jpg|thumb|1913 botanical illustration of ''H.&nbsp;perforatum'' by Jost Fitschen in {{lang|de|Pflanzen der Heimat}}]] ''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.<ref name="Ernst-2003" />{{rp|19}} The current accepted placement of ''H.&nbsp;perforatum'' within its genus can be summarized as follows:<ref name=Robson-2002 />{{rp|62}}

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

=== Phylogeny === ''Hypericum perforatum'' has a chromosome count of 2n = 32. The likely reason for this is that the species is a hybrid between the very closely related ''H.&nbsp;maculatum subsp. immaculatum'' and ''H.&nbsp;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="Ernst-2003" /> {{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.&nbsp;perforatum'' and ''H.&nbsp;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.&nbsp;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.&nbsp;perforatum'' 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.&nbsp;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="Robson-2002"> {{Cite journal |last=Robson |first=Norman |author-link=Norman Robson (botanist) |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=Biodiversity Heritage Library}}</ref>{{rp|64}}

{| class="wikitable" |+Hybrids involving ''H. perforatum<ref name="Robson-2002" />'' !Crossed with !Hybrid name !Chromosome number<ref group="a">Uncertainty in chromosome number notated by "?"</ref> |- |''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" |{{Reflist|group=a}} |}

=== Etymology and common names=== The genus name ''Hypericum'' is possibly derived from the Greek words {{Lang|el|hyper}} (above) and {{Lang|el|eikon}} (picture), in reference to the tradition of hanging the plant over religious icons 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 Latin and refers to the 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 pharmacologist, referred to either it or ''H.&nbsp;empetrifolium'' as ''akuron''.<ref name="Ernst" /> The species was first formally described by Carl Linnaeus in the second tome of ''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, 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 priority for this species is not in question, there are a number of botanical synonyms that were published in the early years of formal 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 illegitimate under the principle of priority. Likewise, the name ''Hypericum officinarum'' by the botanist Heinrich Johann Nepomuk von Crantz in 1763 also postdated Linnaeus' 1753 naming and description and is considered invalid.<ref name="POWO" />

=== Subdivision === 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 infraspecific taxa is difficult because of the many intermediate forms that exist.<ref name="Robson-2002" />{{rp|88}} * ''H. perforatum'' 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'' 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 leaf stalks; the glands on the seed capsule are also distinct.<ref name="Robson-2002" />{{rp|88}} ** ''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 vesicles on their surface. These appear to be adaptations of ssp. ''perforatum'' in response to the mountainous habitats of the region.<ref name="Robson-2002" />{{rp|89}} * ''H. perforatum'' ssp. ''songaricum'' is likely the most primitive after ssp. ''perforatum''. Previously described as a variety by 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="Robson-2002" />{{rp|89}} ** ''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="Robson-2002" />{{rp|89}} * ''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="Robson-2002" />{{rp|89}} ** ''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="Robson-2002" />{{rp|89}} * ''H. perforatum'' ssp. ''chinense'' is found across most of China and was introduced into Japan (under the synonym ''H&nbsp;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="Robson-2002" />{{rp|89}}

==Distribution and habitat== ===Distribution=== [[File:Hypericum perforatum distribution.png|thumb|upright=1.5|Country-level distribution of ''Hypericum perforatum'', based on data from the 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 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 Buryatia. 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 (in 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 been introduced throughout much of Canada,<ref name="USDA">{{cite usda plants|symbol=HYPE |title=Hypericum perforatum |date=1 August 2023}}</ref> as well as in 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 the plant is found in the states of South Australia, Tasmania, Victoria, New South Wales, and Western Australia; in all these states it has been listed as a declared weed, since it renders agricultural land unproductive for grazing. It has been introduced to both the North and South Islands of New Zealand.<ref name="WeedsAustralia">{{cite web|url=https://weeds.org.au/profiles/st-johns-wort/#prosection6|title=St John’s Wort|website=WeedsAustralia |access-date=2026-04-04}}</ref><ref name="POWO" />

===Habitat=== The species can be found in a variety of habitats including open woods, meadows, grasslands, steppe, riverbanks, and stony or grassy hillsides and roadsides. It prefers dry habitats or areas with strong drainage.<ref name="Robson-2002" />{{rp|88}} The species thrives in areas with at least {{convert|760|mm|abbr=on}} of rainfall per year; however, its distribution is restricted by temperatures too low for seed germination or seedling survival: an absolute minimum of −3{{Nbsp}}°C or an annual average of 9{{Nbsp}}°C.<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> Altitudes greater than {{convert|1500|m|abbr=on}}, rainfall less than {{convert|500|mm|abbr=on}}, and daily mean temperatures greater than {{convert|24|C|F}} are also considered limiting thresholds.<ref name="BioactiveMolecules" />

== Ecology == === Reproduction === [[File:Bombus terrestris P1140477a.jpg|thumb|200x200px|''Bombus terrestris'' pollinating the flowers of ''Hypericum perforatum'']] St John's wort reproduces both vegetatively and 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 seeds without fertilization.<ref name="FSControl" /> Its seeds can persist for decades while lying dormant underground in an ecosystem's soil seed bank, germinating after they are disturbed.<ref name="feis" /><ref name="cabi" />

=== Diseases === ''H. perforatum'' is affected by phytoplasma diseases, and when infected with ''Candidatus'' phytoplasma fraxini it shows visible symptoms, including yellowing and deformities called witch's broom. Its chemical profile is also altered: naphthodianthrone, flavonoid, amentoflavone, and pseudohypericin levels are reduced; 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 ''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>

=== 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.<ref name="CanadaAg">{{cite journal |last1=Harris |first1=P. |last2=Peschkin |first2=D. P. |title=Biological 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 ''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.<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, ''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.<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.&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.<ref>{{cite web|url=http://www.bladmineerders.nl/minersf/lepidopteramin/euspilapteryx/auroguttella/auroguttella.htm|title=bladmineerders.nl|author=|date=|website=bladmineerders.nl|access-date=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 ({{convert|17|mm|abbr=on}}) 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 midge, is a small ({{convert|3|mm|abbr=on}}) fly that eats ''H.&nbsp;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 pupates into a mature adult.<ref name="FSControl" />

=== Toxicity === ''Hypericum perforatum'' is 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 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="Colostate">{{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.&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.<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 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.<ref name="Colostate" /><ref name="WeedsAustralia"/>

=== Invasiveness === [[File:Hypericum perforatum field belair park.jpg|thumb|''Hypericum perforatum'' growing prolifically in Belair National Park, South Australia]] Although ''H.&nbsp;perforatum'' is grown commercially in some regions of southeast Europe, it is listed as a noxious weed in more than 20 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 native plant communities and forage vegetation to the extent of making productive land nonviable or becoming an invasive species in natural habitats and ecosystems.<ref name="North West Weeds">{{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 2,4-D, picloram, metsulfuron, and 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 ''Chrysolina quadrigemina'', ''Chrysolina hyperici'', ''Agrilus hyperici'', ''Aplocera plagiata'', and ''Zeuxidiplosis giardi''.<ref name="FSControl" /><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>

==Uses== [[File:Hyperici herba by Danny S. - 001.JPG|thumb|Dried ''Hypericum perforatum'' for use as the herbal drug herba hyperici]]

===Antidepressant effects=== {{Further|Hyperforin}} ''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.<ref>{{cite web|title=Second draft: European Union herbal monograph on Hypericum perforatum L., herba – well-established and traditional use|author=European Medicines Agency, Committee on Herbal Medicinal Products (HMPC)|date=3 March 2021 |url=https://www.ema.europa.eu/en/documents/herbal-opinion/second-draft-european-union-herbal-monograph-hypericum-perforatum-l-herba-traditional-use-revision-1_en.pdf|website=European Medicines Agency|access-date=2025-05-22}}</ref> 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.<ref name="pmid27589952">{{cite journal|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=Systematic Reviews |volume=5 |issue=1 |article-number=148 |doi=10.1186/s13643-016-0325-2 |pmc=5010734 |pmid=27589952 |doi-access=free }}</ref><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><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><ref>{{Cite journal |last1=Zhao |first1=Xin |last2=Zhang |first2=Hong |last3=Wu |first3=Yanyan |last4=Yu |first4=Chun |date=2023 |title=The efficacy and safety of St. John's wort extract in depression therapy compared to SSRIs in adults: A meta-analysis of randomized clinical trials|journal=Advances in Clinical and Experimental Medicine |url=https://advances.umw.edu.pl/en/article/2023/32/2/151/ |volume=32 |issue=2 |pages=151–161 |doi=10.17219/acem/152942 |pmid=36226689 |issn=1899-5276}}</ref> 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.<ref>{{Cite web |title=St. John's Wort and Depression: In Depth |url=https://www.nccih.nih.gov/health/st-johns-wort-and-depression-in-depth |access-date=2026-01-07 |website=NCCIH |language=en}}</ref><ref>{{Cite web |title=St John’s Wort |url=https://my.clevelandclinic.org/health/drugs/9304-st--johns-wort |website=Cleveland Clinic}}</ref> ''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.<ref name="peterson">{{Cite web |last1=Peterson |first1=Bahtya |title=St. John's Wort |date=2025 |url=https://www.ncbi.nlm.nih.gov/books/NBK557465/ |access-date=2025-06-19 |publisher=StatPearls Publishing |pmid=32491397 |last2=Nguyen |first2=Hoang}}</ref><ref name="msk">{{Cite web |date=2022-02-08 |title=St. John's Wort|publisher= Memorial Sloan Kettering Cancer Center |url=https://www.mskcc.org/cancer-care/integrative-medicine/herbs/st-john-wort |access-date=2025-06-19 |language=en}}</ref>

===In traditional medicine=== Common St. John's wort has been used in herbalism for centuries.<ref name="nccih">{{cite web |date=April 2025 |title=St. John's Wort |url=https://www.nccih.nih.gov/health/stjohnswort/ataglance.htm |access-date=24 June 2025 |publisher=National Center for Complementary and Integrative Health, US National Institutes of Health}}</ref> It was used in classical antiquity and was a standard component of ancient concoctions called theriacs, from the Mithridate of Aulus Cornelius Celsus' {{Lang|la|De Medicina}} ({{circa|30}} 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 |work=Toxicology in Antiquity (Second Edition) |pages=161–174 |editor-last=Wexler |editor-first=Philip |url=https://www.sciencedirect.com/science/article/pii/B9780128153390000111 |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 |work=Toxicology in Antiquity (Second Edition) |pages=175–184 |editor-last=Wexler |editor-first=Philip |url=https://www.sciencedirect.com/science/article/pii/B9780128153390000123 |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 |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> The dried flower is crushed to make the compound known as ''herba hyperici''.<ref>World Health Organization, pp. 149, 151.</ref>

[[File:Hypericum perforatum - dyed fabrics.jpg|thumb|175px|Samples of wool 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.<ref name="HarPin">{{cite book |last1=Hardman |first1=Judy |last2=Pinhey |first2=Sally |title=Natural Dyes |date=2018 |publisher=Crowood Press |location=Marlborough, UK |isbn=978-1-84797-100-5 |edition=|orig-year=2000 |page=50}}</ref>

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.<ref name="Dea">{{cite book |last1=Dean |first1=Jenny |title=Wild Colour: How to Grow, Prepare and Use Natural Plant Dyes |date=2010 |publisher=Mitchell Beazley |isbn=978-18453-3-569-4 |edition=|orig-year=1999 |page=97}}</ref> == Inability to treat cancer == There is no clinical evidence that St John's wort is effective to treat cancer.<ref>{{Cite web|date=2022|title=St John's wort and cancer|url=https://www.cancerresearchuk.org/about-cancer/treatment/complementary-alternative-therapies/individual-therapies/st-johns-wort|website=Cancer Research UK|language=en-GB|archive-date=June 12, 2024|archive-url=https://web.archive.org/web/20240612160001/https://www.cancerresearchuk.org/about-cancer/treatment/complementary-alternative-therapies/individual-therapies/st-johns-wort|url-status=live}}</ref><ref>{{Cite web|date=2024|title=Complementary therapies|url=https://www.cancervic.org.au/cancer-information/treatments/common-side-effects/complementary-therapies/herbs-plants.html|website=Cancer Council Victoria|language=en-GB|archive-date=October 3, 2024|archive-url=https://web.archive.org/web/20241003185117/https://www.cancervic.org.au/cancer-information/treatments/common-side-effects/complementary-therapies/herbs-plants.html|url-status=live}}</ref> 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".<ref name="NCI">{{Cite web|date=2024|title=Questions and Answers About St. John's Wort|url=https://www.cancer.gov/about-cancer/treatment/cam/patient/dietary-interactions-pdq#_66_toc|website=National Cancer Institute|language=en-GB|archive-date=October 2, 2024|archive-url=https://web.archive.org/web/20241002035802/https://www.cancer.gov/about-cancer/treatment/cam/patient/dietary-interactions-pdq#_66_toc|url-status=live}}</ref> St John's wort may reduce the efficacy of chemotherapy.<ref name=msk/>

== Interactions with drugs == Use of ''H.&nbsp;perforatum'' may cause significant drug interactions, primarily through PXR activation and CYP3A4 induction linked to its hyperforin content, affecting the efficacy and safety of various medications.<ref name=peterson/><ref name="Nicolussi-2019" />

St. John's wort can interfere with the effects of prescription and over-the-counter drugs in potentially adverse ways by increasing CYP3A4 and CYP2C9 liver enzymes, leading to faster conversion of drugs.<ref name=peterson/><ref name=msk/> Specific consequences may include reduced effectiveness of oral contraceptives, heart medications, HIV drugs, cancer medications, and some anticoagulants;<ref name=peterson/><ref name="nccih" /> other adverse effects may involve breakthrough bleeding when taking oral contraceptives,<ref name=msk/> and decreased effectiveness of immunosuppressants in people with organ transplants.<ref name=peterson/>

The increase in these enzymes 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="Chrubasik-Hausmann-2018">{{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="Nicolussi-2019">{{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="Chrubasik-Hausmann-2018" />

== Adverse effects == Use of ''H.&nbsp;perforatum'' may produce adverse effects when combined with other antidepressants through an increase in brain serotonin levels called ''serotonin syndrome'', which may be life-threatening and is associated with rapid heart rate, acute hypertension, mydriasis, and fever.<ref name=peterson/><ref name=msk/> Photosensitivity and acute neuropathy upon sun exposure, and reduced response to chemotherapy are other possible effects.<ref name=msk/><ref name="Nicolussi-2019" />

Common side effects of St John's wort products are headache, nausea, fatigue, dry mouth, sleepiness, and gastrointestinal upset.<ref name=nccih/><ref name=msk/> It should not be consumed during pregnancy and breastfeeding.<ref name=peterson/><ref name=msk/>

== Regulation == In the United States, St John's wort is considered a dietary supplement by the FDA, is not regulated by the same standards as a prescription drug, and does not have clearly defined mechanisms in people.<ref name=peterson/> == References == {{Reflist}}

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