Editing Hypericum perforatum (section)

==Description==
[[File:Hypericum-perforatum(Blatt).jpg|thumb|Leaf showing translucent glands and dark glands near the edges]]
''Hypericum perforatum'' is an [[herbaceous plant|herbaceous]] [[perennial plant]] with hairless ([[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 [[rhizome]]s.<ref name="Canada" /> The [[Taproot|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 [[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=}}</ref>

It has leaves that attach on [[Phyllotaxis|opposite]] sides of the stems without a stalk ([[Sessility (botany)|sessile]]). The leaves vary in shape from being very narrow and almost grass-like ([[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 ([[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 (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 [[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=}}</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|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'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="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 [[sepal]]s 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 ([[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, {{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 [[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 [[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 [[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 {{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. 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 zone|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. 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]] ([[Anthraquinones|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> The species contains a host of [[essential oil]]s, the bulk of which are [[sesquiterpene]]s.<ref name="Mehta" /> 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}}</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'' !! [[Polar surface area|PSA]] !! [[Acid dissociation constant|pK<sub>a</sub>]] !! Formula !! [[Molecular weight|MW]] !! [[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> !![[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" /> !! [[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>'''[[Phloroglucinol]]s''' (2–5%)</big>
|-
| [[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 || ? || ? || ? || ? || ? || ? || ? || ? || ? || ?
|-
| [[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>'''[[Naphthodianthrone]]s''' (0.03-3%)</big>
|-
| [[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>'''[[Flavonoid]]s''' (2–12%)</big>
|-
| [[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) || ? || ? || ? || ? || ? || ?
|-
| [[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 || ? || ? || ? || ? || ? || ? || ? || ? || ? || ?
|-
| [[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> || ? || ? || ?
|-
| [[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 || ? || ? || ? || ? || ? || ? || ? || ? || ? ||
|-
| [[Kaempferol]] || ? || 2.1±0.6 || 107 || 6.44 || C<sub>15</sub>H<sub>10</sub>O<sub>6</sub> || 286.24 || ? || ? || ? || +/- || ? || ? || ? || ? || ? || ?
|-
| [[Luteolin]] || ? || 2.4±0.65 || 107 || 6.3 || C<sub>15</sub>H<sub>10</sub>O<sub>6</sub> || 286.24 || – || ? || ? || ? || ? || ? || ? || ? || ? || ?
|-
| [[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> || ? || ? || ?
|-
| [[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>
|-
| [[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 || ? || ? || ? || – || ? || ? || ? || ? || ? || ?

|-
| [[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 || [[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> || [[Partition coefficient]].
|-
| PSA || [[Polar surface area]] of the molecule in question in square [[angstroms]] (Å<sup>2</sup>). 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
|-
| <sup>a</sup> || ?
|-
| <sup>b</sup> || ?
|-
| <sup>c</sup> || ?
|}
'''Notes:'''
{{Reflist|group=Note}}