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{{more science citations needed|date = October 2023}}
{{chembox {{chembox
| Verifiedfields = changed
⚫ | Name = Phorbol
| Watchedfields = changed
⚫ | ImageFile = Phorbol.svg
| verifiedrevid = 390502294
<!-- | ImageSize = 250px -->
⚫ | Reference = <ref>'']'', 11th Edition, '''7306'''</ref>
| ImageName = Phorbol
⚫ | Name = Phorbol
⚫ | IUPACName = 1,1a,1b,4,4a,7a,7b,8,9,9a-decahydro-<br />4a,7b,9,9a-tetrahydroxy-3-<br />(hydroxymethyl)-1,1,6,8-tetramethyl-5H-<br />cyclopropabenzazulen-5-one
⚫ | ImageFile = Phorbol.svg
| Section1 = {{Chembox Identifiers
| CASNo = 17673-25-5 | ImageSize =
| ImageName = Phorbol
⚫ | SMILES = OCC1=C((C(C)4C)()<br />4(O)(O)2C)()<br />2(O)(C=C(C)C3=O)<br />()3(O)C1
⚫ | PIN = (1a''R'',1b''S'',4a''R'',7a''S'',9b''S'',8''R'',9''R'',9a''S'')-4a,7b,9,9a-Tetrahydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-1,1a,1b,4,4a,7a,7b,8,9,9a-decahydro-5''H''-cyclopropabenzoazulen-5-one
⚫ }}
| Section2 = {{Chembox Properties | Section1 = {{Chembox Identifiers
| CASNo_Ref = {{cascite|correct|??}}
| Formula = C<sub>20</sub>H<sub>28</sub>O<sub>6</sub>
| CASNo = 17673-25-5
| MolarMass = 364.44 g/mol
| UNII_Ref = {{fdacite|correct|FDA}}
| MeltingPt = 250-251 °C
| UNII = XUZ76S9127
⚫ | SMILES = OCC1=C((C(C)4C)()4(O)(O)2C)()2(O)(C=C(C)C3=O)()3(O)C1
| PubChem = 442070
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 390610
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 8116
| InChI = 1/C20H28O6/c1-9-5-13-18(24,15(9)22)7-11(8-21)6-12-14-17(3,4)20(14,26)16(23)10(2)19(12,13)25/h5-6,10,12-14,16,21,23-26H,7-8H2,1-4H3/t10-,12+,13-,14-,16-,18-,19-,20-/m1/s1
| InChIKey = QGVLYPPODPLXMB-UBTYZVCOBR
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C20H28O6/c1-9-5-13-18(24,15(9)22)7-11(8-21)6-12-14-17(3,4)20(14,26)16(23)10(2)19(12,13)25/h5-6,10,12-14,16,21,23-26H,7-8H2,1-4H3/t10-,12+,13-,14-,16-,18-,19-,20-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = QGVLYPPODPLXMB-UBTYZVCOSA-N
}} }}
| Section2 = {{Chembox Properties
| C=20
| H=28
| O=6
| MeltingPtC = 250 to 251
| MeltingPt_notes =
| Solubility = Soluble in DMSO (25mg/ml), 100% ethanol (25mg/ml), acetone, ether or dimethyl formamide; almost insoluble in aqueous buffers.
⚫ }}
}} }}


'''Phorbol''' is a natural, plant-derived ]. It is a member of the ] family of ]. It was first isolated in 1934 as the ] product of ], which is derived from the seeds of '']''.<ref name="Flaschenträger_1934">{{cite journal | author = Flaschenträger B, v. Wolffersdorff R | title = Über den Giftstoff des Crotonöles. 1. Die Säuren des Crotonöles | journal = Helvetica Chimica Acta | volume = 17 | issue = 1 | pages = 1444–1452 | year = 1934 | pmid = | doi = 10.1002/hlca.193401701179 }}</ref><ref name="Flaschenträger_1942">{{cite journal | author = Flaschenträger B, Wigner G | title = Über den Giftstoff des Crotonöles. V. Die Gewinnung von Crotonharz, Dünnem Öl und Phorbol aus dem Crotonöl durch Alkoholyse | journal = Helvetica Chimica Acta | volume = 25 | issue = 3 | pages = 569–581 | year = 1942 | pmid = | doi = 10.1002/hlca.19420250315 }}</ref><ref name="Kauffmann_1959a">{{cite journal | author = Kauffmann T, Neumann H, Lenhardt K | title = Zur Konstitution des Phorbols, I. Über die reduzierende Gruppe des Phorbols | journal = Chemische Berichte | volume = 92 | issue = 8 | pages = 1715–1726 | year = 1959 | pmid = | doi = 10.1002/cber.19590920802 }}</ref><ref name="Kauffmann_1959B">{{cite journal | author = Kauffmann T, Eisinger A, Jasching W, Lenhardt K | title = Zur Konstitution des Phorbols, I. Über die reduzierende Gruppe des Phorbols | journal = Chemische Berichte | volume = 92 | issue = 8 | pages = 1727–1738 | year = 1959 | pmid = | doi = 10.1002/cber.19590920803 }}</ref><ref name="Tseng_1977">{{cite journal | author = Tseng S-S, Van Duuren BL, Solomon JJ | title = Synthesis of 4a.alpha.-phorbol 9-myristate 9a-acetate and related esters | journal = J. Org. Chem. | volume = 42 | issue = 33 | pages = 3645–3649 | year = 1977 | pmid = | doi = 10.1021/jo00443a002 }}</ref> Phorbol's structure was determined in 1967.<ref name="Hecker_1967">{{cite journal | author = Hecker E, Bartsch H, Bresch H, Gschwendt M, Härle B, Kreibich G, Kubinyi H, Schairer HU, Szczepanski Ch v, Thielmann HW | title = Structure and stereochemistry of the tetracyclic diterpene phorbol from croton tiglium L | journal = Tetrahedron Letters | volume = 8 | issue = 33 | pages = 3165–3170 | year = 1967| pmid = | doi = 10.1016/S0040-4039(01)89890-7 }}</ref><ref name="Pettersen_1967">{{cite journal | author = Pettersen RC, Ferguson G, Crombie L, Games ML, Pointer DJ | title = The structure and stereochemistry of phorbol, diterpene parent of co-carcinogens of croton oil | journal = Chem. Commun. (London) | volume = | issue = | pages = 716 | year = 1967 | pmid = | doi =10.1039/C19670000716 }}</ref> It is very soluble in most polar organic solvents, as well as in water. '''Phorbol''' is a natural, plant-derived ]. It is a member of the ] family of ]. Phorbol was first isolated in 1934 as the ] product of ], which is derived from the seeds of the purging croton, '']''.<ref name="Flaschenträger_1934">{{cite journal |author1=Flaschenträger B |author2=v. Wolffersdorff R | title = Über den Giftstoff des Crotonöles. 1. Die Säuren des Crotonöles | journal = Helvetica Chimica Acta | year = 1934 | volume = 17 | issue = 1 | pages = 1444–1452 | doi = 10.1002/hlca.193401701179 }}</ref><ref name="Flaschenträger_1942">{{cite journal |vauthors=Flaschenträger B, Wigner G | title = Über den Giftstoff des Crotonöles. V. Die Gewinnung von Crotonharz, Dünnem Öl und Phorbol aus dem Crotonöl durch Alkoholyse | journal = Helvetica Chimica Acta | year = 1942 | volume = 25 | issue = 3 | pages = 569–581 | doi = 10.1002/hlca.19420250315 }}</ref><ref name="Kauffmann_1959a">{{cite journal |vauthors=Kauffmann T, Neumann H, Lenhardt K | title = Zur Konstitution des Phorbols, I. Über die reduzierende Gruppe des Phorbols | journal = Chemische Berichte | year = 1959 | volume = 92 | issue = 8 | pages = 1715–1726 | doi = 10.1002/cber.19590920802 }}</ref><ref name="Kauffmann_1959B">{{cite journal |vauthors=Kauffmann T, Eisinger A, Jasching W, Lenhardt K | title = Zur Konstitution des Phorbols, I. Über die reduzierende Gruppe des Phorbols | journal = Chemische Berichte | year = 1959 | volume = 92 | issue = 8 | pages = 1727–1738 | doi = 10.1002/cber.19590920803 }}</ref><ref name="Tseng_1977">{{cite journal |vauthors=Tseng SS, van Duuren BL, Solomon JJ | title = Synthesis of 4aα-Phorbol 9-Myristate 9a-Acetate and Related Esters | journal = J. Org. Chem. | year = 1977 | volume = 42 | issue = 33 | pages = 3645–3649 | doi = 10.1021/jo00443a002 | pmid = 915585 }}</ref> The structure of phorbol was determined in 1967.<ref name="Hecker_1967">{{cite journal |author1=Hecker E |author2=Bartsch H |author3=Bresch H |author4=Gschwendt M |author5=Härle B |author6=Kreibich G |author7=Kubinyi H |author8=Schairer HU |author9=v. Szczepanski C |author10=Thielmann HW | title = Structure and Stereochemistry of the Tetracyclic Diterpene Phorbol from ''Croton tiglium'' L | journal = Tetrahedron Letters | year = 1967 | volume = 8 | issue = 33 | pages = 3165–3170 | doi = 10.1016/S0040-4039(01)89890-7 }}</ref><ref name="Pettersen_1967">{{cite journal |vauthors=Pettersen RC, Ferguson G, Crombie L, Games ML, Pointer DJ | title = The Structure and Stereochemistry of Phorbol, Diterpene Parent of Co-carcinogens of Croton Oil | journal = Chem. Commun. | year = 1967 | volume = 1967 | issue = 14 | pages = 716–717 | doi = 10.1039/C19670000716 }}</ref>
⚫ Various ] have important biological properties, the most notable of which is the capacity to act as ] through activation of ].<ref name="pmid3275491">{{cite journal | author = Blumberg PM | title = Protein Kinase C as the Receptor for the Phorbol Ester Tumor Promoters: Sixth Rhoads Memorial Award Lecture | journal = Cancer Res. | year = 1988 | volume = 48 | issue = 1 | pages = 1–8 | pmid = 3275491 | url = http://cancerres.aacrjournals.org/content/48/1/1.full.pdf }}</ref> They mimic ]s, glycerol derivatives in which two hydroxyl groups have reacted with ]s to form esters. The most common and potent phorbol ester is ] (TPA), also called phorbol-12-myristate-13-acetate (PMA), which is used as a biomedical research tool in contexts such as models of ].


==History and source==
⚫ Various ]s of phorbol have important biological properties, the most notable of which is the capacity to act as tumor promoters through activation of ].<ref name="pmid3275491">{{cite journal | author = Blumberg PM | title = Protein kinase C as the receptor for the phorbol ester tumor promoters: sixth Rhoads memorial award lecture | journal = Cancer Res. | volume = 48 | issue = 1 | pages = 1–8 | year = 1988 | pmid = 3275491 | doi = | issn = }}</ref> They mimic ]s, glycerol derivatives in which two hydroxyl groups have reacted with ]s to form esters. The most common phorbol ester is ] (TPA), also called phorbol-12-myristate-13-acetate (PMA), which is used as biomedical research tool in models of ]. PMA, together with ionomycin, can also be used to stimulate T-cell cytokine production, and is used in protocols for intracellular staining of these cytokines <ref name="eBioscience protocols">{{http://www.ebioscience.com/ebioscience/appls/FCI.htm}}</ref>
Phorbol is a natural product found in many plants, especially those of the ] and ] families.<ref name=Wang2015>{{cite journal|last1=Wang|first1=Xiao-Yang|last2=Liu|first2=Li-Ping|last3=Qin|first3=Guo-Wei|last4=Kang|first4=Ting-Guo|title=Tigliane Diterpenoids from the Euphorbiaceae and Thymelaeaceae Families|journal=Chemical Reviews|date=2015|volume=115|issue=9|pages=2975–3011|doi=10.1021/cr200397n|pmid=25906056}}</ref><ref>{{cite journal|last1=Beutler|first1=John A.|last2=Alvarado|first2=Ada Belinda|last3=McCloud|first3=Thomas G.|title=Distribution of phorbol ester bioactivity in the euphorbiaceae|journal=Phytotherapy Research|date=1989|volume=3|issue=5|pages=188–192|doi=10.1002/ptr.2650030507|s2cid=85408071}}</ref> Phorbol is the active constituent of the highly toxic New World tropical ] or beach apple, ''Hippomane mancinella''.<ref>{{Cite journal
|last1=Adolf |first1=W
|last2=Hecker |first2=E
|title=On the active principles of the spurge family. X. Skin irritants, cocarcingoens, and cryptic carcinogens from the latex of the manchineel tree
|journal=J Nat Prod
|volume=47
|year=1984
|issue=3
|pages=482–496
|pmid=6481361
|doi=10.1021/np50033a015
}}</ref> It is very soluble in most ] organic ]s, as well as in water. In the manchineel, this leads to an additional exposure risk during rain, where liquid splashing from an undamaged tree may also be injurious. Contact with the tree or consumption of its fruit can lead to symptoms such as severe pain and swelling.<ref>{{cite journal|last1=Strickland|first1=Nicola H|title=Eating a manchineel "beach apple"|journal=BMJ|date=August 12, 2000|volume=321|issue=7258|page=428|doi=10.1136/bmj.321.7258.428|pmc=1127797|pmid=10938053}}</ref><ref>{{cite journal|last1=Blue|first1=Lauren M|last2=Sailing|first2=Christopher|last3=DeNapoles|first3=Christopher|last4=Fondots|first4=Jordan|last5=Johnson|first5=Edward S|title=Manchineel Dermatitis in North American Students in the Caribbean|journal=Journal of Travel Medicine|date=2011|volume=18|issue=6|pages=422–424|doi=10.1111/j.1708-8305.2011.00568.x|pmid=22017721|doi-access=free}}</ref>{{primary source inline|date = October 2023}}


The ], ''Croton tiglium'', is the source of ] from which phorbol was initially isolated. Its seeds and oil have been used for hundreds of years in traditional medicine, generally as a purgative, and the seeds were mentioned in Chinese herbal texts 2000 years ago.<ref name=Zhang2013>{{cite journal|last1=Zhang|first1=Xiao-Long|last2=Wang|first2=Lun|last3=Li|first3=Fu|last4=Yu|first4=Kai|last5=Wang|first5=Ming-Kui|title=Cytotoxic Phorbol Esters of Croton tiglium|journal=Journal of Natural Products|date=2013|volume=13|issue=5|pages=858–864|doi=10.1021/np300832n|pmid=23701597}}</ref> The purgative effects of the oil are largely attributed to the high percentage of phorbol esters contained in the oil. Phorbol was isolated from ''C. tiglium'' seeds in 1934.<ref name="Flaschenträger_1934"/><ref name="Flaschenträger_1942"/><ref name="Kauffmann_1959a"/><ref name="Kauffmann_1959B"/><ref name="Tseng_1977"/> The structure of the compound was determined in 1967,<ref name="Hecker_1967"/><ref name="Pettersen_1967"/> and a total synthesis was described in 2015.<ref name=Kawamura>{{cite journal | doi = 10.1038/nature17153| pmid = 27007853| title = Nineteen-step total synthesis of (+)-phorbol| journal = Nature| volume = 532| issue = 7597| pages = 90–3| year = 2016| last1 = Kawamura| first1 = Shuhei| last2 = Chu| first2 = Hang| last3 = Felding| first3 = Jakob| last4 = Baran| first4 = Phil S.| bibcode = 2016Natur.532...90K| pmc=4833603}}.</ref>
⚫ ==References==
⚫ {{Reflist|2}}


==Mechanism of action==
⚫ *Merck Index, 11th Edition, 7306
Phorbol derivatives work primarily by interacting with protein kinase C (PKC), although they can interact with other phospholipid membrane receptors.<ref name=Goel2007>{{cite journal|last1=Goel|first1=Gunjan|last2=Makkar|first2=Harinder P.S.|last3=Francis|first3=George|last4=Becker|first4=Klaus|title=Phorbol Esters: Structure, Biological Activity, and Toxicity in Animals|journal=International Journal of Toxicology|date=July 2007|volume=26|issue=4|pages=279–288|doi=10.1080/10915810701464641|pmid=17661218|citeseerx=10.1.1.320.6537|s2cid=11550625|url = https://journals.sagepub.com/doi/epub/10.1080/10915810701464641 | access-date = 27 October 2023}}</ref> The esters bind to PKC in a similar way to its natural ligand, ], and activate the kinase.<ref name=Li2010>{{cite journal|last1=Li|first1=Cai-Yan|last2=Devappa|first2=Rakshit K|last3=Liu|first3=Jian-Xin|last4=Lv|first4=Jian-Min|last5=Makkar|first5=HPS|last6=Becker|first6=K|title=Toxicity of Jatropha curcas phorbol esters in mice|journal=Food and Chemical Toxicology|date=February 2010|volume=48|issue=2|pages=620–625|doi=10.1016/j.fct.2009.11.042|pmid=19944127}}</ref> Diacylglycerol is degraded quickly by the body, allowing PKC to be reversibly activated. When phorbol esters bind to the receptor, they are not degraded as efficiently by the body, leading to constitutively active PK.<ref name=Goel2007/> PKC is involved in a number of important cell signaling pathways. Thus, phorbol ester exposure can show a wide range of results.
]
The main results of phorbol exposure are tumor promotion and inflammatory response. Although phorbol is not a carcinogen itself, it greatly enhances the action of other substances and promotes tumor proliferation. PKC is a key component in biological pathways controlling cell growth and differentiation. When phorbol esters bind to PKC, cell proliferation pathways are activated. This effect greatly promotes tumors when the cells are exposed to even a sub-carcinogenic amount of a substance.<ref name=Goel2007/>
PKC is also involved in activation of inflammation pathways such as the ] pathway. Thus, exposure to phorbol products can induce an inflammatory response in tissues.<ref>{{cite journal|last1=Moscat|first1=Jorge|last2=Diaz-Meco|first2=María T|last3=Rennert|first3=Paul|title=NF-κB activation by protein kinase C isoforms and B-cell function|journal=EMBO Reports|date=January 2003|volume=4|issue=1|pages=31–36|doi=10.1038/sj.embor.embor704|pmid=12524517|pmc=1315804}}</ref><!--NOT A SUITABLE REFERENCE. THIS TECHNICAL REPORT AIMS TO SELL PRODUCTS. MOREOVER, CONTENT IS UNREFEREED, AND COMPANY NO LONGER EXISTS. <ref>{{cite web|title=NF-κB and Inflammation|url=http://www.sigmaaldrich.com/technical-documents/articles/biofiles/nf-b-and-inflammation.html|website=Sigma-Aldrich|publisher=Sigma-Aldrich|access-date=7 May 2017}}</ref>--> Symptoms can include edema and pain, especially to the skin and mucous membranes.<ref name=Wang2015/>
While phorbol itself does not have irritant activity, nearly all phorbol esters are highly irritant, with a wide range of half-maximal inhibitory concentration (]) values.<ref name=Wang2015/> The median lethal dose (]) of phorbol esters for male mice was found to be about 27&nbsp;mg/kg, with the mice showing hemorrhage and congestion of pulmonary blood vessels, as well as lesions throughout the body.<ref name=Li2010/>


==External links== ==Total synthesis==
A ] of ] phorbol was developed in 2015. While this synthesis will not replace natural isolation products, it will enable researchers to create phorbol ] for use in research, especially creating phorbol ] that can be evaluated for anti-cancer activity.<ref name=Kawamura/> Previously, the difficulty with synthesizing phorbol had been creating C–C bonds, especially in the six-membered ring at the top of the molecule. This synthesis starts from (+)-], and uses a series of 19 steps to eventually create (+)-phorbol.<ref>{{cite journal | doi = 10.1021/ja00206a050| title = Studies on tumor promoters. 8. The synthesis of phorbol| journal = Journal of the American Chemical Society| volume = 111| issue = 24| pages = 8957| year = 1989| last1 = Wender| first1 = Paul A.| last2 = Kogen| first2 = Hiroshi| last3 = Lee| first3 = Hee Yoon| last4 = Munger| first4 = John D.| last5 = Wilhelm| first5 = Robert S.| last6 = Williams| first6 = Peter D.}}</ref><ref>{{cite journal | doi = 10.1021/ja9706256| title = The First Formal Asymmetric Synthesis of Phorbol| journal = Journal of the American Chemical Society| volume = 119| issue = 33| pages = 7897| year = 1997| last1 = Wender| first1 = Paul A.| last2 = Rice| first2 = Kenneth D.| last3 = Schnute| first3 = Mark E.}}</ref><ref name=Kawamura/>
⚫ {{Commonscat|Phorbols}}
:]{{clear-left}}

==Uses in biomedical research==
Because of their mechanism of action, phorbol esters can be used to study tumor proliferation and pain response.{{fact|date = October 2023}} TPA is most commonly used in the laboratory to induce a cellular response.{{fact|date = October 2023}} For example, TPA can be used to measure response to pain and test compounds that may mitigate the inflammatory response.<ref>{{cite journal|last1=Medeiros|first1=Rodrigo|last2=Otuki|first2=Michel F|last3=Avellar|first3=Maria Christina W|last4=Calixto|first4=João|title=Mechanisms underlying the inhibitory actions of the pentacyclic triterpene α-amyrin in the mouse skin inflammation induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetate|journal=European Journal of Pharmacology|date=March 2007|volume=22|issue=2–3|pages=227–235|doi=10.1016/j.ejphar.2006.12.005}}</ref> TPA and other phorbol esters can also be used to induce tumor formation and to study mechanism of action.<ref name=Wang2015/> TPA, together with ], can also be used to stimulate T-cell activation, proliferation, and cytokine production, and is used in protocols for intracellular staining of these cytokines.{{fact|date = October 2023}}<!--COMMERCIAL SOURCE; NOT SUITABLE FOR ENCYCLOPEDIC CITATION <ref name="urlFlow Cytometry Intracellular Staining Guide">{{cite web | url = http://www.ebioscience.com/resources/best-protocols/flow-cytometry/flow-cytometry-intracellular-staining-quick-guide.htm | title = Flow Cytometry Intracellular Staining Guide | date = | website = | publisher = eBioscience, Inc. | access-date = 2011-09-25 }}</ref>-->

===Possible and purported medicinal uses===
The phorbol ester ] reportedly has ''in vitro'' anti-cancer, antiviral, and antibacterial activities.<ref name=Wang2015/> The phorbol derivatives in croton oil are used in folk medicine, with purported purgative, counter-irritant, or ] activities.<!--THIS IS ANOTHER COMMERCIAL SITE, AND ONE THAT ALSO NO LONGER EXISTS <ref>{{cite web|title=Croton Oil|url=http://oilhealthbenefits.com/croton-oil/|website=OilHealthBenefits|publisher=OilHealthBenefits|date=2014-07-12}}</ref>--><ref>{{cite journal|last1=Pal|first1=Prince Kumar|last2=Nandi|first2=Manmath Kumar|last3=Singh|first3=Narendra Kumar|title=Detoxification of Croton tiglium L. seeds by Ayurvedic process of Śodhana|journal=Ancient Science of Life|date=Jan–Mar 2014|volume=33|issue=3|pages=157–161|doi=10.4103/0257-7941.144619|pmid=25538350|pmc=4264303 |doi-access=free }}</ref>{{better source|date = October 2023}}

⚫ == References ==
⚫ {{Reflist}}

==Further reading==
* {{cite journal|last1=Goel|first1=Gunjan|last2=Makkar|first2=Harinder P.S.|last3=Francis|first3=George|last4=Becker|first4=Klaus|title=Phorbol Esters: Structure, Biological Activity, and Toxicity in Animals|journal=International Journal of Toxicology|date=July 2007|volume=26|issue=4|pages=279–288|doi=10.1080/10915810701464641|pmid=17661218|citeseerx=10.1.1.320.6537|s2cid=11550625|url = https://journals.sagepub.com/doi/epub/10.1080/10915810701464641 | access-date = 27 October 2023}}
* {{cite journal|last1=Kikkawa|first1=Ushio| date = June 2019 | orig-date = November 2018 | title=The Story of PKC: A Discovery Marked by Unexpected Twists and Turns| journal=IUBMB Life| volume=71 |issue=6| pages=697–705| doi=10.1002/iub.1963| pmid= | citeseerx= |s2cid= | doi-access=free}}

== External links ==
* {{MeshName|Phorbols}} * {{MeshName|Phorbols}}

⚫ {{Commons category|Phorbols}}


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