8-Prenylnaringenin
{{cs1 config|name-list-style=vanc}}
{{Chembox
| ImageFile = 8-Prenylnaringenin.svg
| ImageSize = 200px
| ImageAlt = Chemical structure of 8-prenylnaringenin
| IUPACName = (2S)-4′,5,7-Trihydroxy-8-(3-methylbut-2-en-1-yl)flavan-4-one
| SystematicName = (2S)-5,7-Dihydroxy-2-(4-hydroxyphenyl)-8-(3-methylbut-2-en-1-yl)-2,3-dihydro-4H-1-benzopyran-4-one
| OtherNames = Hopein; Flavaprenin; Sophoraflavanone B
|Section1={{Chembox Identifiers
| CASNo = 53846-50-7
| CASNo_Ref = {{cascite|correct|CAS}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 5L872SZR8X
| PubChem = 480764
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 50207
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C18023
| ChemSpiderID = 421848
| SMILES = CC(=CCC1=C2C(=C(C=C1O)O)C(=O)C[C@H](O2)C3=CC=C(C=C3)O)C
| InChI = 1/C20H20O5/c1-11(2)3-8-14-15(22)9-16(23)19-17(24)10-18(25-20(14)19)12-4-6-13(21)7-5-12/h3-7,9,18,21-23H,8,10H2,1-2H3/t18-/m0/s1
| InChIKey = LPEPZZAVFJPLNZ-SFHVURJKBX
| StdInChI = 1S/C20H20O5/c1-11(2)3-8-14-15(22)9-16(23)19-17(24)10-18(25-20(14)19)12-4-6-13(21)7-5-12/h3-7,9,18,21-23H,8,10H2,1-2H3/t18-/m0/s1
| StdInChIKey = LPEPZZAVFJPLNZ-SFHVURJKSA-N
}}
|Section2={{Chembox Properties
| C=20|H=20|O=5
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|Section3={{Chembox Hazards
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8-Prenylnaringenin (8-PN; also known as flavaprenin, (S)-8-dimethylallylnaringenin, hopein, or sophoraflavanone B) is a prenylflavonoid phytoestrogen. It is reported to be the most estrogenic phytoestrogen known.{{cite journal | vauthors = Keiler AM, Zierau O, Kretzschmar G | title = Hop extracts and hop substances in treatment of menopausal complaints | journal = Planta Med. | volume = 79 | issue = 7 | pages = 576–9 | year = 2013 | pmid = 23512496 | doi = 10.1055/s-0032-1328330 | doi-access = free }} The compound is equipotent at the two forms of estrogen receptors, ERα and ERβ,{{cite journal | vauthors = Hajirahimkhan A, Dietz BM, Bolton JL | title = Botanical modulation of menopausal symptoms: mechanisms of action? | journal = Planta Med. | volume = 79 | issue = 7 | pages = 538–53 | year = 2013 | pmid = 23408273 | pmc = 3800090 | doi = 10.1055/s-0032-1328187 }} and it acts as a full agonist of ERα.{{Citation | last = Green | first = Sarah E | title = In Vitro Comparison of Estrogenic Activities of Popular Women's Health Botanicals | year = 2015 | url = https://indigo.uic.edu/handle/10027/19647 | type = thesis | access-date = 2016-01-01 | archive-url = https://web.archive.org/web/20160222183517/https://indigo.uic.edu/handle/10027/19647 | archive-date = 2016-02-22 | url-status = dead }} Its effects are similar to those of estradiol, but it is considerably less potent in comparison.
8-PN is found in hops (Humulus lupulus) and in beer, and is responsible for the estrogenic effects of the former.{{cite journal|pmid=14744951|year=2004|last1=Nikolic|first1=D|last2=Li|first2=Y|last3=Chadwick|first3=LR|last4=Grubjesic|first4=S|last5=Schwab|first5=P|last6=Metz|first6=P|last7=Van Breemen|first7=RB|title=Metabolism of 8-prenylnaringenin, a potent phytoestrogen from hops (Humulus lupulus), by human liver microsomes|volume=32|issue=2|pages=272–9|doi=10.1124/dmd.32.2.272|journal=Drug Metabolism and Disposition}} It can be produced from isoxanthohumol in fungal cells cultures,{{cite journal |doi=10.1021/jf2011722|pmid=21634799|title=Production of 8-Prenylnaringenin from Isoxanthohumol through Biotransformation by Fungi Cells|journal=Journal of Agricultural and Food Chemistry|volume=59|issue=13|pages=7419–26|year=2011|last1=Fu|first1=Ming-Liang|last2=Wang|first2=Wei|last3=Chen|first3=Feng|last4=Dong|first4=Ya-Chen|last5=Liu|first5=Xiao-jie|last6=Ni|first6=Hui|last7=Chen|first7=Qi-he}} and by flora in the human intestine.
Properties
=Estrogenic=
8-PN was shown to preserve bone density and has been demonstrated to reduce hot flashes.{{cite journal | title=The hop phytoestrogen, 8-prenylnaringenin, reverses the ovariectomy-induced rise in skin temperature in an animal model of menopausal hot flushes. | journal=Journal of Endocrinology | volume=191 | issue=2 | pages=399–405 | date=November 15, 2012 | author=Bowe, James | doi=10.1677/joe.1.06919| pmid=17088409 | pmc=1635969 }} 8-PN also induces the secretion of prolactin, and increases other estrogenic responses. The compound binds to and activates ERα more times{{clarify|reason="more times" sounds like a specific number is missing; and it's unclear whether this means more *tightly* or its binding more effectively activates|date=April 2023}} than it does to ERβ.
This prenylflavanoid has drawn interest in the study of hormone replacement therapy, and it is comparable to some selective estrogen-receptor modulators.{{cite journal | title=The hop phytoestrogen, 8-prenylnaringenin, reverses the ovariectomy-induced rise in skin temperature in an animal model of menopausal hot flushes. | journal=Journal of Endocrinology | date=November 2006 | author=Bowe | doi=10.1677/joe.1.06919 | pmid=17088409 | pmc=1635969 | volume=191 | issue=2 | pages=399–405}}
In an in vivo study, 8-PN has activated proliferation of mammary cells. At the concentration found in beer, it is unlikely to have an estrogenic effect in breast tissue.{{cite journal|doi=10.1002/mnfr.200900519|pmid=20486208|pmc=3856213|title=Disposition of hop prenylflavonoids in human breast tissue|year=2010|last1=Bolca|first1=Selin|last2=Li|first2=Jinghu|last3=Nikolic|first3=Dejan|last4=Roche|first4=Nathalie|last5=Blondeel|first5=Phillip|last6=Possemiers|first6=Sam|last7=De Keukeleire|first7=Denis|last8=Bracke|first8=Marc|last9=Heyerick|first9=Arne|last10=Van Breemen|first10=Richard B.|last11=Depypere|first11=Herman|journal=Molecular Nutrition & Food Research|volume=54|issue=2 |pages=S284–94}} Similar to other estrogens, 8-PN induces the expression of the progesterone receptor in various tissues.
Luteinizing hormone (LH) and follicle stimulating hormone (FSH) are suppressed by 8-PN, indicating that it possesses antigonadotropic properties. 8-PN adversely affects male sperm.{{cite web | url=http://news.bbc.co.uk/2/hi/health/2082449.stm | title=Environmental 'hormones' wreck sperm | work=BBC News | date=July 2, 2002 | access-date=2013-06-26}} The role 8-PN plays in fertility requires further research.
=Other=
In an in vitro study, 8-PN and synthetic derivatives demonstrated anticancer properties.{{cite journal | title=Antiproliferative activity and synthesis of 8-prenylnaringenin derivatives by demethylation of 7-O- and 4′-O-substituted isoxanthohumols | journal=Med Chem Res | date=January 7, 2012 | author=Anioł, Mirosław | doi=10.1007/s00044-011-9967-8 | pmid=23087590 | pmc=3474914 | volume=21 | issue=12 | pages=4230–4238}} More recently, a radioligand binding study showed enhancements in GABAA receptor activity by 8-PN{{cite journal|last1=Benkherouf|first1=Ali Y.|last2=Soini|first2=Sanna L.|last3=Stompor|first3=Monika|last4=Uusi-Oukari|first4=Mikko|date=February 2019|title=Positive allosteric modulation of native and recombinant GABAA receptors by hops prenylflavonoids|journal=European Journal of Pharmacology|volume=852|pages=34–41|doi=10.1016/j.ejphar.2019.02.034|pmid=30797788|s2cid=73456325|issn=0014-2999}}
Prenylflavonoids from hops, including 8-PN, are ingredients in some breast enlargement supplements, though there is no evidence of its effectiveness for this purpose.{{cite journal |doi=10.1097/01.PRS.0000141495.14284.8B |title=Breast-Enhancing Pills: Myth and Reality |year=2004 |last1=Chalfoun |first1=Charbel |last2=McDaniel |first2=Candice |last3=Motarjem |first3=Pejman |last4=Evans |first4=Gregory R. D. |journal=Plastic and Reconstructive Surgery |pages=1330–3 |pmid=15457059 |author5=Plastic Surgery Educational Foundation DATA Committee |volume=114 |issue=5}}
Chemistry
The enzyme naringenin 8-dimethylallyltransferase uses dimethylallyl diphosphate and (−)-(2S)-naringenin to produce diphosphate and sophoraflavanone B (8-prenylnaringenin).
The enzyme 8-dimethylallylnaringenin 2'-hydroxylase uses sophoraflavanone B (8-prenylnaringenin), NADPH, H+ and O2 to produce leachianone G, NADP+ and H2O.
Synthesized derivatives of 8-PN are: 7,4′-di-O-methyl-8-prenylnaringenin; 7-O-pentyl-8-prenylnaringenin; 7,4′-Di-O-allyl-8-prenylnaringenin; 7,4′-Di-O-acetyl-8-prenylnaringenin; and 7,4′-Di-O-palmitoyl-8-prenylnaringenin.
8-Neopentylnaringenin and 8-n-heptylnaringenin are synthetic derivatives of 8-PN.{{cite journal|url=http://www.physoc.org/proceedings/abstract/Proc%20Physiol%20Soc%2015PC142|title=The effect of synthetic analogues of the phyto-oestrogen 8-prenylnaringenin on tail skin temperature in a rat hot flush model|journal=Proceedings of the Physiological Society|year=2009|last1=Breen|first1=L.|last2=Sugden|first2=D.|last3=Heyerick|first3=A.|last4=O'Byrne|first4=K.|last5=Milligan|first5=S.|archive-url=https://web.archive.org/web/20131203124326/http://www.physoc.org/proceedings/abstract/Proc%20Physiol%20Soc%2015PC142|archive-date=3 December 2013|url-status=dead}}
Etymology
There is another compound, 8-isopentenylnaringenin, also known as sophoraflavanone B, from Sophora flavescens, that could properly be called 8-prenylnaringenin by scientific naming convention.
References
{{Reflist|refs=
{{cite journal | title=The pharmacognosy of Humulus lupulus L. (hops) with an emphasis on estrogenic properties | journal=Phytomedicine | date=July 1, 2005 | author=Chadwick | author2=Pauli | author3=Farnsworth | doi=10.1016/j.phymed.2004.07.006 | pmid=16360942 | pmc=1852439 | volume=13 | issue=1–2 | pages=119–31}}
{{cite journal|title=In vivo estrogenic comparisons of Trifolium pratense (red clover) Humulus lupulus (hops), and the pure compounds isoxanthohumol and 8-prenylnaringenin|pmc=2574795|year=2008|last1=Overk|first1=CR|last2=Guo|first2=J|last3=Chadwick|first3=LR|last4=Lantvit|first4=DD|last5=Minassi|first5=A|last6=Appendino|first6=G|last7=Chen|first7=SN|last8=Lankin|first8=DC|last9=Farnsworth|first9=NR|last10=Pauli|first10=GF|last11=Van Breemen|first11=RB|last12=Bolton|first12=JL|volume=176|issue=1|pages=30–39|doi=10.1016/j.cbi.2008.06.005|journal=Chemico-Biological Interactions|pmid=18619951|bibcode=2008CBI...176...30O }}
{{cite journal | title=Comparison of the In Vitro Estrogenic Activities of Compounds from Hops (Humulus lupulus) and Red Clover (Trifolium pratense) | journal=J Agric Food Chem |date=August 2005 | volume=53 | issue=16| pages=6246–6253 | doi=10.1021/jf050448p | last1=Overk | first1=C. R. |last2=Yao | first2=Ping | last3=Chadwick | first3=Lucas R. | last4=Nikolic | first4=Dejan | last5=Sun | first5=Yongkai | last6=Cuendet | first6=Muriel A. | last7=Deng | first7=Yunfan | last8=Hedayat | first8=A. S. | last9=Pauli | first9=Guido F. | last10=Farnsworth | first10=Norman R. |last11=van Breemen | first11=Richard B. | last12=Bolton | first12=Judy L. | pmid=16076101 | pmc=1815392 }}
{{cite journal | title=Pharmacokinetics and systemic endocrine effects of the phyto-oestrogen 8-prenylnaringenin after single oral doses to postmenopausal women | author=Rad | journal=British Journal of Clinical Pharmacology | date=September 1, 2006 | volume=62 | issue=3 | pages=288–296 | doi=10.1111/j.1365-2125.2006.02656.x | pmc=1885137 | pmid=16934044| last2=Hümpel | last3=Schaefer | last4=Schoemaker | last5=Schleuning | last6=Cohen | last7=Burggraaf }}
{{cite journal|title=The Prenylflavonoid Isoxanthohumol from Hops (Humulus lupulus L.) Is Activated into the Potent Phytoestrogen 8-Prenylnaringenin In Vitro and in the Human Intestine|journal=Journal of Nutrition|date=July 2006 |volume=136| issue= 7| pages=1862–1867|publisher=American Society for Nutrition|pmid=16772450|last1=Possemiers|first1=S.|last2=Bolca|first2=S.|last3=Grootaert|first3=C.|last4=Heyerick|first4=A.|last5=Decroos|first5=K.|last6=Dhooge|first6=W.|last7=De Keukeleire|first7=D.|last8=Rabot|first8=S.|last9=Verstraete|first9=W.|last10=Van de Wiele|first10=T.|doi=10.1093/jn/136.7.1862 |doi-access=free}}
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{{Phytoestrogens}}
{{Estrogenics}}
{{Flavanones}}
{{DEFAULTSORT:Prenylnaringenin, 8-}}