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{{Chembox {{Chembox
| Verifiedfields = changed
⚫ | ImageFile = Angelicin.png
| Watchedfields = changed
| verifiedrevid = 457810850
| Name =
⚫ | ImageFile = Angelicin 200.svg
| ImageSize = 200px | ImageSize = 200px
| IUPACName = 2''H''-Furochromen-2-one | PIN = 2''H''-Furobenzopyran-2-one
| OtherNames = Isopsoralen | OtherNames = Isopsoralen, 2''H''-furochromen-2-one, furochromen-2-one
| pronounce = ˈeɪn.dʒəlaɪ.sɪn
| Section1 = {{Chembox Identifiers | Section1 = {{Chembox Identifiers
| CASNo = <!-- blanked - oldvalue: 523-50-2 --> | CASNo = 523-50-2
| CASNo_Ref = {{cascite|correct|CAS}} | CASNo_Ref = {{cascite|correct|CAS}}
| UNII_Ref = {{fdacite|correct|FDA}}
⚫ | ChEBI = 28928
| UNII = CZZ080D7BD
| ChEBI_Ref = {{ebicite|correct|EBI}}
⚫ | ChEBI = 28928
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C11H6O3/c12-10-4-2-7-1-3-9-8(5-6-13-9)11(7)14-10/h1-6H | StdInChI = 1S/C11H6O3/c12-10-4-2-7-1-3-9-8(5-6-13-9)11(7)14-10/h1-6H
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = XDROKJSWHURZGO-UHFFFAOYSA-N | StdInChIKey = XDROKJSWHURZGO-UHFFFAOYSA-N
| PubChem = 10658 | PubChem = 10658
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 53569 | ChEMBL = 53569
| KEGG_Ref = {{keggcite|correct|kegg}} | KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = <!-- blanked - oldvalue: C09060 --> | KEGG = C09060
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 10208
| SMILES = O=C\2Oc3c1ccoc1ccc3/C=C/2 | ChemSpiderID = 10208
| SMILES = O=C\2Oc3c1ccoc1ccc3/C=C/2
| InChI = InChI=1S/C11H6O3/c12-10-4-2-7-1-3-9-8(5-6-13-9)11(7)14-10/h1-6H | InChI = InChI=1S/C11H6O3/c12-10-4-2-7-1-3-9-8(5-6-13-9)11(7)14-10/h1-6H
}} }}
| Section2 = {{Chembox Properties | Section2 = {{Chembox Properties
| C=11|H=6|O=3 | C=11 | H=6 | O=3
| Appearance = | Appearance = pale yellow crystals <ref name='nmr & appearance' />
| Density = | Density =
| MeltingPt = | MeltingPt = 134°C
| BoilingPt = | BoilingPt = 362.6°C
| Solubility = | Solubility = 10 mM in DMSO
| LogP = 1.97<ref name="biobyte">{{Cite web|url=http://www.biobyte.com|title=BioByte|website=www.biobyte.com|access-date=2018-03-15}}</ref>
}} }}
| Section3 = {{Chembox Hazards | Section3 = {{Chembox Hazards
| MainHazards = | MainHazards = photosensitizer, vesicant, carcinogen
| FlashPt = | FlashPt = 173.1°C
| Autoignition = | AutoignitionPt =
}} }}
| Section4 =
| Section5 =
| Section6 =
}} }}


'''Angelicin''' is the parent compound in a family of naturally occurring organic compounds known as the angular ]s. Structurally, it can be considered as ] fused with a furan moiety in the 7,8-position. Angelicin is commonly found in certain ] and ] plant species such as '']''. It has a skin permeability coefficient (Log''K<sub>p</sub>'') of -2.46.<ref name="biobyte" /> The maximum absorption is observed at 300&nbsp;nm.<ref>{{Cite journal|last1=Bordin|first1=F.|last2=Dall'Acqua|first2=F.|last3=Guiotto|first3=A.|date=December 1991|title=Angelicins, angular analogs of psoralens: chemistry, photochemical, photobiological and phototherapeutic properties|journal=Pharmacology & Therapeutics|volume=52|issue=3|pages=331–363|issn=0163-7258|pmid=1820581|doi=10.1016/0163-7258(91)90031-G}}</ref> The <sup>1</sup>HNMR spectrum is available;<ref name='nmr & appearance' /> the infrared and mass spectra of angelicin can be found in this . The sublimation of angelicin occurs at 120&nbsp;°C and the pressure of 0.13 Pa.<ref>{{Cite journal|last1=Böhme|first1=Horst|last2=Severin|first2=Theodor|title=Optische Untersuchungen an Cumarinen Mitteilung: Die Ultraviolettabsorption einiger Cumarine pflanzlicher Herkunft|journal=Archiv der Pharmazie|language=en|volume=290|issue=10|pages=486–494|doi=10.1002/ardp.19572901010|pmid=13471015|issn=1521-4184|year=1957|s2cid=84020911}}</ref> Angelicin is a ].
'''Angelicin''' is a ]. It can be found in '']''. It is present in the ] (Angelicin plus ] radiation).

== History and etymology ==
Humans have used plants rich in angelicin for centuries. The earliest known record dates back to 3000 BC when ancient Egyptians applied the oil and sap of local '']'' species exposing their skin to sunlight to cure ]. In meantime, tribes in India used '']'' which contained ], the isomer of angelicin. Humans also attempted to harvest the plants as an alternative food source. However, most of them turned out to be unpalatable and toxic such as '']'' due to the ability to irritate skin and damage internal organs.<ref>{{Cite journal|last1=Lenković|first1=Maja|last2=Cabrijan|first2=Leo|last3=Gruber|first3=Franjo|last4=Saftić|first4=Marina|last5=Stanić Zgombić|first5=Zrinka|last6=Stasić|first6=Adalbert|last7=Peharda|first7=Vesna|date=October 2008|title=Phytophotodermatitis in Rijeka region, Croatia|journal=Collegium Antropologicum|volume=32|issue=Suppl 2 |pages=203–205|issn=0350-6134|pmid=19138025}}</ref>
]
The name "angelicin" stems from the aforementioned plant, ''Angelica''. This Latin name originated in medieval Europe where this plant was also used as a universal treatment to many types of disease not mentioning the ]. At this time, people believed that the plant could prevent the soul from being taken over by sorcery, curse and evil spirit (add reference). ''Angelica'' would have appeared in a dream with an angel explaining its applications, hence the name. Ironically, it was later discovered that the plant's oil is toxic when utilized in large quantities particularly when the plant was fresh.<ref>{{Cite news|url=https://www.herbal-supplement-resource.com/angelica-benefits.html|title=Angelica Herb Uses, Health Benefits and Side Effects|work=The Herbal Resource|access-date=2018-03-16|language=en-US}}</ref>

The species of plants where angelicin is found was introduced in Britain in the 19th century. Currently, it can be found in ] and some parts of the ] and ]. Because of the toxicity of certain plant parts and the ability of plant to proliferate, it is included in the list of ].<ref>{{Cite news|url=http://drmgoeswild.com/giant-hogweed-a-new-contribution-to-understanding-this-plant-in-the-uk/|title=Giant Hogweed: a new contribution to understanding this plant in the UK|date=2014-01-09|work=Dr M Goes Wild|access-date=2018-03-16|language=en-US}}</ref>

The leaves of ''Angelica archangelica,'' which are rich in angelicin, are used to extract the compound.<ref>{{Cite journal|last1=Steck|first1=Warren|last2=Bailey|first2=B. K.|title=Leaf coumarins of Angelicaarchangelica|journal=Canadian Journal of Chemistry|volume=47|issue=13|pages=2425–2430|doi=10.1139/v69-396|year=1969|doi-access=free}}</ref> There were multiple studies on the toxicity of angelicin one of which showed that the compound elicits ] in hamster cells exposed to 320-380&nbsp;nm UV light.<ref>{{Cite journal|date=1977-06-01|title=Chromosome damage in chinese hamster cells sensitized to near-ultraviolet light by psoralen and angelicin|journal=Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis|language=en|volume=43|issue=3|pages=377–385|doi=10.1016/0027-5107(77)90059-8|pmid=561302|issn=0027-5107|last1=Ashwood-Smith|first1=M.J.|last2=Grant|first2=E.L.|last3=Heddle|first3=J.A.|last4=Friedman|first4=G.B.}}</ref> The chromosomal aberrations were shown to be also induced in humans.

Nowadays, it is debated whether ''Angelica'' should be considered toxic. However, it is certain that the toxicity is dependent on the dose of angelicin administered and is solely the matter of experts when it comes to its application.

== Biological synthesis ==
[[File:The general biosynthesis pathway of angular furanocoumarins.jpg|alt=loefpihegruofpeijjl|thumb|The general biosynthesis of angular furanocoumarins.
Angelicin is illustrated as a final product.<ref name="general" />
|left|361x361px]]

The biosynthesis of angelicin can be described as a variation in the biological synthesis of furanocoumarins. It begins from the capture of organic carbon by photosynthesis and the formation of carbohydrates. Subsequently, the carbohydrates become the substrates of the ] where they are converted to phenylalanine and tyrosine. Enzymes such as ammonialyases, methylases and hydroxylases then transform these amino acids to cinnamic acid derivatives which undergo ] yielding coumarins. The coumarins can undergo further reactions such as ] and oxidation to give multiple furanocoumarins one of which is angelicin.<ref name="general">{{Cite book|url=https://books.google.com/books?id=eC3LBAAAQBAJ&q=angelicin|title=Plant Biochemistry|last1=Bonner|first1=James|last2=Varner|first2=J. E.|date=2016-07-29|publisher=Elsevier|isbn=9781483267807|language=en}}</ref>
[[File:The first steps of angelicin biosynthesis.jpg|alt=The first steps of angelicin biosynthesis|left|thumb|249x249px|The synthesis of
''p''-coumaric acid from phenylalanine.<ref name="coumar" />
]]
Here, the biosynthesis of angelicin is described in more detail starting at L-phenylalanine as a precursor. The phenylalanine undergoes a non-oxidative deamination by ] (PAL) to ''trans''-]. Afterwards, the ''trans''-cinnamic acid is hydroxylated at the ''para'' position by ] (C4H) which utilizes NADPH, H<sup>+</sup> and O<sub>2</sub>. The product, ], is then converted to ], the important intermediate of biosynthesis pathway.<ref name="coumar">{{Cite book|url=https://books.google.com/books?id=IZCaBQAAQBAJ&q=Recent+Advances+in+Redox+Active+Plant+and+Microbial+Products&pg=PA363|title=Recent Advances in Redox Active Plant and Microbial Products: From Basic Chemistry to Widespread Applications in Medicine and Agriculture|last1=Jacob|first1=Claus|last2=Kirsch|first2=Gilbert|last3=Slusarenko|first3=Alan|last4=Winyard|first4=Paul G.|last5=Burkholz|first5=Torsten|date=2014-11-25|publisher=Springer|isbn=9789401789530|language=en}}</ref>
]
4-Coumaric acid 2-hydroxylase (C2’H) hydroxylates the ''p''-coumaric acid at the ''ortho'' position. Notably, this reaction uses alpha-ketoglutarate which is reduced to succinate both of which are involved in the ]. The newly formed ''trans''-dihydrocinnamic acid undergoes a photochemical isomerization to a ''cis'' isomer which spontaneously ] to yield umbeliferone.<ref name="umbi">{{Cite book|title=The Biology of Plant Phenolics|last=Arnold|first=J.W.E.|publisher=Biochemical education|year=1976|volume=4 |issue=1}}</ref>
]
Subsequently, umbelliferone 6-] (PT) couples umbelliferone with prenyl diphosphate to give osthenol and pyrophosphate. Osthenol is oxidized to (+)-columbianetin by (+)-columbianetin synthase (CS), a putative ], although the details of this reaction are not clear. The biosynthesis is terminated with the oxidation of (+)-columbianetin yielding angelicin by ] (AS) which is also considered as the enzyme of cytochrome P450 family.<ref name=":0">{{Cite journal|last1=Larbat|first1=Romain|last2=Hehn|first2=Alain|last3=Hans|first3=Joachim|last4=Schneider|first4=Sarah|last5=Jugdé|first5=Hélène|last6=Schneider|first6=Bernd|last7=Matern|first7=Ulrich|last8=Bourgaud|first8=Frédéric|date=2009-02-20|title=Isolation and functional characterization of CYP71AJ4 encoding for the first P450 monooxygenase of angular furanocoumarin biosynthesis|journal=The Journal of Biological Chemistry|volume=284|issue=8|pages=4776–4785|doi=10.1074/jbc.M807351200|issn=0021-9258|pmid=19098286|s2cid=33058404|url=https://hal.archives-ouvertes.fr/hal-01738063/file/Larbat%20et%20al%202009.pdf|doi-access=free}}</ref>

It is noteworthy that the biosynthesis of angelicin diverges at the umbelliferone as it is also converted to psoralen, the isomer of angelicin. In fact, psoralen, from which the family of linear furanocoumarins descends, is by far much more abundant in plants than angelicin. As a result, most herbivorous insects are resistant to psoralen. Now, it is increasingly recognized that plants devised the pathway leading to angelicin as an alternative defense mechanism. For example, angelicin enhances the toxicity of psoralen by acting as an inhibitor of the detoxifying cytochrome P450 in insects.<ref>{{Cite journal|last1=Stanjek|first1=Volker|last2=Boland|first2=Wilhelm|date=1998-09-09|title=Biosynthesis of Angular Furanocoumarins: Mechanism and Stereochemistry of the Oxidative Dealkylation of Columbianetin to Angelicin in Heracleum mantegazzianum (Apiaceae)|journal=Helvetica Chimica Acta|volume=81|issue=9|pages=1596–1607|doi=10.1002/(SICI)1522-2675(19980909)81:9<1596::AID-HLCA1596>3.0.CO;2-F}}</ref> Moreover, the comparison of the protein sequences of ] and angelicin synthase shows a 70% ] overall and 40% identity in the substrate recognition sites.<ref name=":0" /> This implies that the biosynthesis of angelicin is a relatively recently evolved trait.

== Chemical synthesis ==
]
]
]
Iodination of commercially available ] (7-hydroxycoumarin) yields 7-hydroxy-8-iodocoumarin. ] can be introduced into hydroxyl of 7-hydroxy-8-iodocoumarin, which is used to create ] or vaginidiol with an isopropyl ] and commercially available epoxy aldehydes. Subsequent acid-catalysed fragmentation of vaginol with ] in ] yields angelicin.<ref name="synth">{{Cite journal|last1=Zou|first1=Yefen|last2=Lobera|first2=Mercedes|last3=Snider|first3=Barry B.|date=2005-03-04|title=Synthesis of 2,3-dihydro-3-hydroxy-2-hydroxylalkylbenzofurans from epoxy aldehydes. One-step syntheses of brosimacutin G, vaginidiol, vaginol, smyrindiol, xanthoarnol, and Avicenol A. Biomimetic syntheses of angelicin and psoralen|journal=The Journal of Organic Chemistry|volume=70|issue=5|pages=1761–1770|doi=10.1021/jo047974k|issn=0022-3263|pmid=15730299}}</ref>

The compound can be isolated from natural sources, albeit this affords a low yield due to the prevalence of other furanocoumarins. The popular technique is air drying the aerial parts and ground roots of plant followed by ''n''-hexane extraction and column chromatography over silica gel.<ref name='nmr & appearance'>{{Cite journal|last1=Dehghan|first1=Hossein|last2=Sarrafi|first2=Yaghoub|last3=Salehi|first3=Peyman|last4=Ebrahimi|first4=Samad Nejad|date=2017-04-01|title=α-Glucosidase inhibitory and antioxidant activity of furanocoumarins from Heracleum persicum|journal=]|language=en|volume=26|issue=4|pages=849–855|doi=10.1007/s00044-017-1796-y|s2cid=31293666|issn=1054-2523}}</ref><ref>{{Cite journal|last1=Shulˈts|first1=E. E.|last2=Ganbaatar|first2=Zh|last3=Petrova|first3=T. N.|last4=Shakirov|first4=M. M.|last5=Bagryanskaya|first5=I. Yu|last6=Taraskin|first6=V. V.|last7=Radnaeva|first7=L. D.|last8=Otgonsuren|first8=D.|last9=Pokrovskii|first9=A. G.|date=2012-05-01|title=Plant coumarins. IX.* Phenolic compounds of Ferulopsis hystrix growing in Mongolia. Cytotoxic activity of 8,9-dihydrofurocoumarins|journal=Chemistry of Natural Compounds|language=en|volume=48|issue=2|pages=211–217|doi=10.1007/s10600-012-0207-3|s2cid=46726721|issn=0009-3130}}</ref>

== Medical use ==
Angelicin derivatives are used to treat ] and ]. One way of treating these diseases is by photochemotherapy (]) which combines UV irradiation with ] chemical.<ref name="Young 237–247">{{Cite journal|last=Young|first=A. R.|date=June 1990|title=Photocarcinogenicity of psoralens used in PUVA treatment: present status in mouse and man|journal=Journal of Photochemistry and Photobiology B: Biology|volume=6|issue=1–2|pages=237–247|issn=1011-1344|pmid=2121937|doi=10.1016/1011-1344(90)85093-C}}</ref><ref name="Matz 73–80">{{Cite journal|last=Matz|first=Hagit|date=January 2010|title=Phototherapy for psoriasis: what to choose and how to use: facts and controversies|journal=Clinics in Dermatology|volume=28|issue=1|pages=73–80|doi=10.1016/j.clindermatol.2009.04.003|issn=1879-1131|pmid=20082955}}</ref> In most cases the 4,5’-dimethylangelicin is applied owing to its firm binding and specificity to DNA. Also, it was shown that it is actively inhibits the synthesis of nucleic acids in tumor cells thereby decreasing their growth.<ref>{{Cite journal|last1=Bordin|first1=F.|last2=Carlassare|first2=F.|last3=Baccichetti|first3=F.|last4=Guiotto|first4=A.|last5=Rodighiero|first5=P.|last6=Vedaldi|first6=D.|last7=Dall‘Acqua|first7=F.|date=1979-06-01|title=4,5'-Dimethylangelicin: A New Dna-Photobinding Monofunctional Agent*|journal=Photochemistry and Photobiology|language=en|volume=29|issue=6|pages=1063–1070|doi=10.1111/j.1751-1097.1979.tb07821.x|pmid=388472|s2cid=40307307 |issn=1751-1097}}</ref>

In PUVA, angelicin is less popular than psoralen, although both furanocoumarins are photosensitizing and used in couple with long-wave UV irradiation. Angelicin and psoralen are used in other skin disorders such as vitiligo and ]. DNA photobinding is the most studied aspect of the photobiology and photochemistry of angelicin. According to the mechanism, long-range UV light triggers angelicin to bind to the pyrimidine bases of DNA in the same manner as psoralen.<ref>{{Cite journal|date=1978-04-01|title=Investigation on the dark interaction between furocoumarins and DNA|journal=Chemico-Biological Interactions|language=en|volume=21|issue=1|pages=103–115|doi=10.1016/0009-2797(78)90071-6|pmid=566637|issn=0009-2797|last1=Dall'Acqua|first1=F.|last2=Terbojevich|first2=M.|last3=Marciani|first3=S.|last4=Vedaldi|first4=D.|last5=Recher|first5=M.}}</ref> In this way, the inhibition of DNA replication via the formation of ] can occur. This might be the basis for the desired therapeutic effect as in the case of psoralen derivatives.<ref name="Young 237–247"/>

However, extreme care should be taken while using PUVA due to the side effects it may bring. Therefore, this type of treatment is sometimes used as a last resort and often corticosteroids are used instead.<ref name="Matz 73–80"/> One of the main adverse effects of PUVA is ] which can be tackled by heteroanalogues of angelicin. For example, recently researchers have shown that if furan ring is replaced by 1-substituted ] or ] ring, the new angelicin heteroanalogues show virtually no phototoxicity.<ref>{{Cite journal|last1=Mosti|first1=L.|last2=Lo Presti|first2=E.|last3=Menozzi|first3=G.|last4=Marzano|first4=C.|last5=Baccichetti|first5=F.|last6=Falcone|first6=G.|last7=Filippelli|first7=W.|last8=Piucci|first8=B.|date=August 1998|title=Synthesis of angelicin heteroanalogues: preliminary photobiological and pharmacological studies|journal=Farmaco (Societa Chimica Italiana: 1989)|volume=53|issue=8–9|pages=602–610|issn=0014-827X|pmid=10081825|doi=10.1016/S0014-827X(98)00076-7|hdl=11577/2470046|hdl-access=free}}</ref>

== Interaction with biomolecules ==
]
It was shown that angelicin exhibits a multifaceted effect on various biomolecules which stem from the compound's structure and ]. For example, the planar structure allows angelicin to ] between the DNA bases. When exposed to ultraviolet light, it undergoes a C<sub>4</sub>-photo] reaction with thymine and cytosine forming a monoadduct. The double bonds of angelicin involved in this reaction are the 3,4 and 4’,5’.<ref name="timo">{{Cite journal|last1=Caffieri|first1=S.|last2=Lucchini|first2=V.|last3=Rodighiero|first3=P.|last4=Miolo|first4=G.|last5=Dall'Acqua|first5=F.|date=November 1988|title=3,4 and 4',5'-photocycloadducts between 4'-methylangelicin and thymine from DNA|journal=Photochemistry and Photobiology|volume=48|issue=5|pages=573–577|issn=0031-8655|pmid=3241830|doi=10.1111/j.1751-1097.1988.tb02866.x|s2cid=32844266 }}</ref> However, the rest of the angelicin's aromatic system cannot react with the pyrimidine of complementary strand owing to the unfavorable alignment of reactive double bonds.<ref>{{Cite journal|last1=Dall'Acqua|first1=F.|last2=Marciani|first2=S.|last3=Ciavatta|first3=L.|last4=Rodighiero|first4=G.|title=Formation of inter-strand cross-linkings in the photoreactions between furanocoumarins and DNA|journal=Zeitschrift für Naturforschung B|date=1971|volume=26 |issue=6|pages=561–569|doi=10.1515/znb-1971-0613|pmid=4397973|doi-access=free}}</ref> Lipids are also susceptible to the photoinduced reactions with angelicin which can be either aerobic or anaerobic. The aerobic reactions cause lipid peroxidation <ref>{{Cite journal|last1=Dall'Acqua|first1=F.|last2=Martelli|first2=P.|date=February 1991|title=Photosensitizing action of furocoumarins on membrane components and consequent intracellular events|journal=Journal of Photochemistry and Photobiology B: Biology|volume=8|issue=3|pages=235–254|issn=1011-1344|pmid=1904925|doi=10.1016/1011-1344(91)80082-S}}</ref> whereas the anaerobic pathway leads to the conjugation of angelicin with unsaturated fatty acid chains such as ] in a manner similar to the formation of pyrimidine adducts.<ref name="photo">{{Cite journal|date=1988-12-01|title=Photoaddition of angelicin to linolenic acid methyl ester|journal=Journal of Photochemistry and Photobiology B: Biology|language=en|volume=2|issue=4|pages=515–521|doi=10.1016/1011-1344(88)85080-2|pmid=3150003|issn=1011-1344|last1=Caffieri|first1=S.|last2=Daga|first2=A.|last3=Vedaldi|first3=D.|last4=Dall'Acqua|first4=F.}}</ref>
]
Proteins were demonstrated to interact with angelicin in a non-covalent fashion. For instance, there is a measurable affinity of angelicin towards human serum albumin (19.10 × 10<sup>4</sup> mol<sup>−1</sup>L<sup>−1</sup>) which has one non-covalent binding site per angelicin molecule. The ultraviolet light (365&nbsp;nm) facilitates its covalent binding to proteins which is enhanced in the presence of oxygen. At this wavelength, angelicin can also modify certain amino acids.<ref>{{Cite journal|last1=Veronese|first1=FM|last2=Bevilacqua|first2=R|last3=Schiavon|first3=O|last4=Rodighiero|first4=G|date=1979|title=Drug-protein interaction: plasma protein binding of furocoumarins.|journal=Il Farmaco; Edizione Scientifica|language=en|volume=34|issue=8|pages=716–25|issn=0430-0920|pmid=467637}}</ref><ref>{{Cite journal|last1=Veronese|first1=F. M.|last2=Schiavon|first2=O.|last3=Bevilacqua|first3=R.|last4=Bordin|first4=F.|last5=Rodighiero|first5=G.|date=1982-07-01|title=Photoinactivation of Enzymes by Linear and Angular Furocoumarins|journal=Photochemistry and Photobiology|language=en|volume=36|issue=1|pages=25–30|doi=10.1111/j.1751-1097.1982.tb04335.x|pmid=6287507|s2cid=42986954 |issn=1751-1097}}</ref><ref>{{Cite journal|last1=Veronese|first1=F. M.|last2=Schiavon|first2=O.|last3=Bevilacqua|first3=R.|last4=Bordin|first4=F.|last5=Rodighiero|first5=G.|date=1981-09-01|title=The Effect of Psoralens and Angelicins on Proteins in the Presence of Uv-a Irradiation|journal=Photochemistry and Photobiology|language=en|volume=34|issue=3|pages=351–354|doi=10.1111/j.1751-1097.1981.tb09369.x|pmid=7280051|issn=1751-1097}}</ref>

== Toxicity ==
According to the ] of Sigma-Aldrich,<ref>{{Cite journal|title=Material Safety Data Sheet|url=https://www.chemblink.com/MSDS/MSDSFiles/523-50-2_Sigma-Aldrich.pdf|journal=Sigma-Aldrich}}</ref> the ] of angelicin is 322&nbsp;mg/kg which shows acute toxicity if orally administered to rats. The possible consequences are alteration in ] and ], ] and ].

Angelicin demonstrates phototoxic and ] effects when in contact with skin. It enhances the sensitivity of skin to UV light <ref name="gorgus">E. Gorgus, C. Lohr, N. Raquet, S. Guth, and D. Schrenk. ''''. Food and Chemical Toxicology, 48(1):93–98, 2010.</ref> leading to severe skin damage such as ] and ]s.<ref>B. V. Davidov A. Ya. Potapenko, V. L. Sukhorukov. ''.'' Experientia 40, pages 264–265, 1982.</ref><ref name="lohr">Christiane Lohr, Nicole Raquet, and Dieter Schrenk. . Toxicology in Vitro, 24(2):558–566, 2010.</ref> Upon irradiation with UV light of longer wavelength, angelicin forms DNA monoadducts which can cause skin cancer.<ref name="lohr" /> In contrast, the isomer of angelicin, psoralen, was reported to be five to ten times more active than angelicin and ] . This impedes DNA replication more prominently due to the inability for the two strands of DNA helix to separate.<ref name=":02">{{Cite journal|last=Alley|first=Amanda|date=August 1987|journal=Food and Chemical Toxicology|volume=25|issue=8|pages=634–635|doi=10.1016/0278-6915(87)90033-0|title=Parsnips and furocoumarins}}</ref> Both psoralen and angelicin can be used in cancer therapeutics to suppress DNA replication in tumor cells and induce ] – as mentioned in medical use – but they should be handled with care as they can cause ] in healthy cells as a side effect.<ref name="gorgus" /><ref name=":02" />

In mammalian cell cultures, angelicin showed ]ic and ] effects while playing a role of strong inhibitor of drug metabolism.<ref name=":1">{{Cite journal|last1=Baumgart|first1=Annette|last2=Schmidt|first2=Melanie|last3=Schmitz|first3=Hans-Joachim|last4=Schrenk|first4=Dieter|date=15 February 2005|title=Natural furocoumarins as inducers and inhibitors of cytochrome P450 1A1 in rat hepatocytes|journal=Biochemical Pharmacology|volume=69|issue=4|pages=657–667|doi=10.1016/j.bcp.2004.11.017|pmid=15670584}}</ref> The inhibition is due to the fact that angelicin decreases the activity and expression of ] which is regulated by ]s (AhR). There are three hypotheses proposed to explain the phenomenon:<ref name=":1" />
# Angelicin attenuates the ] performed by CYP1A1 regardless the presence of UV light.
# Angelicin triggers the ] of CYP1A1 by activation of AhR when no UV light is available.
# Angelicin leads to CYP1A1 gene expression without the involvement of AhR.
The phototoxic properties of angelicin were deployed by its use as a natural pesticide and disinfectant. Note that it is difficult to readily determine whether only angelicin poses the highest risk of phototoxicity and photomutagenicity as in plants angelicin always occurs in a mixture with angelicin derivatives, psoralen and other furanocoumarins. Moreover, the furanocoumarin composition of most plant species is not definitely known as well as the toxic properties of some furanocoumarins.<ref name="lohr" />


==References== ==References==
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