Editing Hypericum perforatum (section)

== Uses ==
=== Traditional medicine ===
[[File:Hyperici herba by Danny S. - 001.JPG|thumb|Dried ''Hypericum perforatum'' for use as the [[Herbal medicine|herbal drug]] herba hyperici]]
Common St. John's wort has been used in [[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 [[classical antiquity]] and was a standard component of ancient concoctions called [[theriac]]s, from the [[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 |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 crushed to make the medicine known as herba hyperici.<ref>World Health Organization, pp. 149, 151.</ref>

=== Medical research ===
==== 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>

A 2016 review found that use of St John's wort for mild and moderate depression was better than placebo for improving depression symptoms and comparable to antidepressant medication.<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 |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 [[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>

St John's wort appears to be more effective than placebo and as effective as standard antidepressant medications for mild and moderate depression.<ref name="nccih" /> A 2015 meta-analysis review concluded that it is more effective than placebo in treating depression, is as effective as standard antidepressants, and has fewer [[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>

Hyperforin, a phytochemical produced by St John's wort, has effects on [[cell culture]]s [[in vitro]] that may indicate antidepressant properties, although its instability causes uncertainty about its biological effects.<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|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>

====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>{{Cite web|date=2022|title=St. John's Wort|url=https://www.mskcc.org/cancer-care/integrative-medicine/herbs/st-john-wort|website=Memorial Sloan Kettering Cancer Center|language=en-GB|archive-date=June 21, 2024|archive-url=https://web.archive.org/web/20240621164025/https://www.mskcc.org/cancer-care/integrative-medicine/herbs/st-john-wort|url-status=live}}</ref>

==== Interactions with drugs and other side effects ====
''H. perforatum'' has been demonstrated to cause significant drug interactions, primarily through [[Pregnane X receptor|PXR]] activation and [[CYP3A4]] induction linked to its hyperforin content, affecting the efficacy and safety of various medications.<ref name="Nicolussi-2019" />

St. John's wort can [[Drug interaction|interfere]] with the effects of prescription and [[Over-the-counter drug|over-the-counter]] drugs in potentially adverse ways by increasing [[CYP3A4]] and [[CYP2C9]] liver enzymes, leading to faster conversion of drugs.<ref>{{Cite journal |last=Komoroski |first=Bernard J. |last2=Zhang |first2=Shimin |last3=Cai |first3=Hongbo |last4=Hutzler |first4=J. Matthew |last5=Frye |first5=Reginald |last6=Tracy |first6=Timothy S. |last7=Strom |first7=Stephen C. |last8=Lehmann |first8=Thomas |last9=Ang |first9=Catharina Y. W. |last10=Cui |first10=Yan Yan |last11=Venkataramanan |first11=Raman|date=2004 |title=Induction and inhibition of cytochromes P450 by the St. John's wort constituent hyperforin in human hepatocyte cultures |url=https://pubmed.ncbi.nlm.nih.gov/15100173/ |journal=Drug Metabolism and Disposition: The Biological Fate of Chemicals |volume=32 |issue=5 |pages=512–518 |doi=10.1124/dmd.32.5.512 |issn=0090-9556 |pmid=15100173}}</ref> Specific consequences may include reduced effectiveness of [[Oral contraceptive pill|oral contraceptives]], heart medications, [[HIV/AIDS|HIV]] drugs, cancer medications, and some [[anticoagulant]]s;<ref name="nccih" /> other adverse effects may involve [[Intermenstrual bleeding|breakthrough bleeding]] when taking oral contraceptives, and decreased effectiveness of [[Immunosuppressive drug|immunosuppressants]] in people with [[Organ transplantation|organ transplants]].<ref name="Nicolussi-2019" />

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" />

The most common side effects of St John's wort products (besides drug interactions) are stomach pain, fatigue, and restlessness. Other more rare effects include [[Photosensitivity in humans|photosensitivity]] and skin irritation. Photosensitivity is linked to [[hypericin]] content.<ref name="Nicolussi-2019" />

===Regulation===
In the United States, St John's wort is considered a [[dietary supplement]] by the [[Food and Drug Administration|FDA]], is not regulated by the same standards as a [[prescription drug]], and does not have clearly defined [[mechanism of action|mechanisms]] in people.<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 ''[[Eleutherococcus senticosus]]'' is sold as an antidepressant under the name {{Lang|zh|Shūgān Jiěyù Jiāonáng}} ({{Lang-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> 
[[File:Hypericum perforatum - dyed fabrics.jpg|thumb|175px|Samples of wool [[Dyeing|dyed]] using ''H. perforatum'']]

===Dyeing pigment===
The plant 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 |ref=|page=50}}</ref>

The flowers produce a series of four different shades on wool, if used in the correct sequence. Wool [[mordant]]ed 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>