Chemical in plants
Apigenin[ 1] Apigenin Names IUPAC name 4′,5,7-Trihydroxyflavone
Systematic IUPAC name 5,7-Dihydroxy-2-(4-hydroxyphenyl)-4H -1-benzopyran-4-one
Other namesApigenine; Chamomile; Apigenol; Spigenin; Versulin; C.I. Natural Yellow 1
Identifiers ChEBI ChEMBL ChemSpider DrugBank ECHA InfoCard 100.007.540 EC Number KEGG UNII InChI=1S/C15H10O5/c16-9-3-1-8(2-4-9)13-7-12(19)15-11(18)5-10(17)6-14(15)20-13/h1-7,16-18H
Y Key: KZNIFHPLKGYRTM-UHFFFAOYSA-N
Y InChI=1/C15H10O5/c16-9-3-1-8(2-4-9)13-7-12(19)15-11(18)5-10(17)6-14(15)20-13/h1-7,16-18H
Key: KZNIFHPLKGYRTM-UHFFFAOYAX
Properties C 15 H 10 O 5 Molar mass −1 Appearance Yellow crystalline solid Melting point 345 to 350 °C (653 to 662 °F; 618 to 623 K) UV-vis (λmax )267, 296sh, 336 nm in methanol[ 2] Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
Apigenin (4′,5,7-trihydroxyflavone), found in many plants, is aflavone compound that is theaglycone of several naturally occurringglycosides . It is a yellow crystalline solid that has been used to dye wool.
Apigenin is abundant inparsley ,celery ,celeriac , andchamomile flowers . It occurs in many fruits and vegetables, with the highest concentrations in dried and fresh parsley.
Apigenin is found in many fruits and vegetables, but parsley, celery,celeriac , and chamomile tea are the most common sources. Apigenin is particularly abundant in the flowers of chamomile plants, constituting 68% of totalflavonoids .[ 3] mg apigenin per gram. The apigenin content of fresh parsley is reportedly 215 mg per 100 grams, which is much higher than the next highest food source.[ 4]
In vitro benzodiazepine site onGABAA receptors.[ 5] [ 6] [ 7]
Apigenin is biosynthetically derived from the generalphenylpropanoid pathway and the flavone synthesis pathway.[ 8] L-tyrosine , both products of theShikimate pathway .[ 9] phenylalanine ammonia lyase to make cinnamate, followed by oxidation at thepara position bycinnamate 4-hydroxylase to producep -coumarate. As L-tyrosine is already oxidized at thepara position, it skips this oxidation and is simply deaminated bytyrosine ammonia lyase to arrive atp -coumarate.[ 10] 4-coumarate CoA ligase substitutes coenzyme A at the carboxy group ofp -coumarate. Entering the flavone synthesis pathway, the type IIIpolyketide synthase enzymechalcone synthase uses consecutive condensations of three equivalents ofmalonyl-CoA followed by aromatization to convertp -coumaroyl-CoA tochalcone .[ 11] Chalcone isomerase then isomerizes the product to close the pyrone ring to makenaringenin . Finally, a flavanone synthase enzyme oxidizes naringenin to apigenin.[ 12] 2+ , and ascorbate as cofactors and FNS II, a membrane bound, NADPH dependent cytochrome p450 monooxygenase.[ 13]
The naturally occurring glycosides formed by the combination of apigenin with sugars include:[citation needed
Some foods contain relatively high amounts of apigenin:[ 15]
Product Apigenin(milligrams per 100 grams) Parsley, dried 4503.5 Parsley, fresh 215.5 Celery hearts, green 19.1 Rutabagas, raw 4
^ Merck Index 763 .^ The Systematic Identification of Flavonoids. Mabry et al, 1970, page 81 ^ Venigalla M, Gyengesi E, Münch G (August 2015)."Curcumin and Apigenin – novel and promising therapeutics against chronic neuroinflammation in Alzheimer's disease" .Neural Regeneration Research .10 (8):1181– 5.doi :10.4103/1673-5374.162686 PMC 4590215 PMID 26487830 . ^ "Flavonoids" .Linus Pauling Institute , Oregon State University. November 2015. Retrieved26 January 2021 .^ Viola H, Wasowski C, Levi de Stein M, et al. (June 1995). "Apigenin, a component ofMatricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects".Planta Medica .61 (3):213– 216.Bibcode :1995PlMed..61..213V .doi :10.1055/s-2006-958058 .ISSN 0032-0943 .PMID 7617761 . ^ Dekermendjian K, Kahnberg P, Witt MR, et al. (21 October 1999). "Structure-activity relationships and molecular modeling analysis of flavonoids binding to the benzodiazepine site of the rat brain GABA(A) receptor complex".Journal of Medicinal Chemistry .42 (21):4343– 4350.doi :10.1021/jm991010h .ISSN 0022-2623 .PMID 10543878 . ^ Avallone R, Zanoli P, Puia G, et al. (1 June 2000). "Pharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla".Biochemical Pharmacology .59 (11):1387– 1394.doi :10.1016/s0006-2952(00)00264-1 .hdl :11380/1207274 ISSN 0006-2952 .PMID 10751547 . ^ Forkmann G (January 1991)."Flavonoids as Flower Pigments: The Formation of the Natural Spectrum and its Extension by Genetic Engineering" .Plant Breeding .106 (1):1– 26.Bibcode :1991PBree.106....1F .doi :10.1111/j.1439-0523.1991.tb00474.x ISSN 0179-9541 . ^ Herrmann KM (January 1995)."The shikimate pathway as an entry to aromatic secondary metabolism" .Plant Physiology .107 (1):7– 12.doi :10.1104/pp.107.1.7 .PMC 161158 PMID 7870841 . ^ Lee H, Kim BG, Kim M, et al. (September 2015)."Biosynthesis of Two Flavones, Apigenin and Genkwanin, in Escherichia coli" .Journal of Microbiology and Biotechnology .25 (9):1442– 8.doi :10.4014/jmb.1503.03011 PMID 25975614 . ^ Austin MB, Noel JP (February 2003). "The chalcone synthase superfamily of type III polyketide synthases".Natural Product Reports .20 (1):79– 110.CiteSeerX 10.1.1.131.8158 doi :10.1039/b100917f .PMID 12636085 . ^ Martens S, Forkmann G, Matern U, et al. (September 2001). "Cloning of parsley flavone synthase I".Phytochemistry .58 (1):43– 6.Bibcode :2001PChem..58...43M .doi :10.1016/S0031-9422(01)00191-1 .PMID 11524111 . ^ Leonard E, Yan Y, Lim KH, et al. (December 2005)."Investigation of two distinct flavone synthases for plant-specific flavone biosynthesis inSaccharomyces cerevisiae " .Applied and Environmental Microbiology .71 (12):8241– 8.Bibcode :2005ApEnM..71.8241L .doi :10.1128/AEM.71.12.8241-8248.2005 .PMC 1317445 PMID 16332809 . ^ Meyer H, Bolarinwa A, Wolfram G, et al. (2006)."Bioavailability of apigenin from apiin-rich parsley in humans" Annals of Nutrition & Metabolism .50 (3):167– 72.doi :10.1159/000090736 .PMID 16407641 .S2CID 8223136 . ^ USDA Database for the Flavonoid Content of Selected Foods, Release 3 (2011)
Aglycones
Monohydroxyflavone Dihydroxyflavones Trihydroxyflavones Tetrahydroxyflavones Pentahydroxyflavones O-methylated flavones
Glycosides
of apigenin of baicalein of hypolaetin of luteolin
Acetylated Sulfated glycosides Polymers Drugs
ER Tooltip Estrogen receptor
Agonists Steroidal: 2-Hydroxyestradiol 2-Hydroxyestrone 3-Methyl-19-methyleneandrosta-3,5-dien-17β-ol 3α-Androstanediol 3α,5α-Dihydrolevonorgestrel 3β,5α-Dihydrolevonorgestrel 3α-Hydroxytibolone 3β-Hydroxytibolone 3β-Androstanediol 4-Androstenediol 4-Androstenedione 4-Fluoroestradiol 4-Hydroxyestradiol 4-Hydroxyestrone 4-Methoxyestradiol 4-Methoxyestrone 5-Androstenediol 7-Oxo-DHEA 7α-Hydroxy-DHEA 7α-Methylestradiol 7β-Hydroxyepiandrosterone 8,9-Dehydroestradiol 8,9-Dehydroestrone 8β-VE2 10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED) 11β-Chloromethylestradiol 11β-Methoxyestradiol 15α-Hydroxyestradiol 16-Ketoestradiol 16-Ketoestrone 16α-Fluoroestradiol 16α-Hydroxy-DHEA 16α-Hydroxyestrone 16α-Iodoestradiol 16α-LE2 16β-Hydroxyestrone 16β,17α-Epiestriol (16β-hydroxy-17α-estradiol) 17α-Estradiol (alfatradiol )17α-Dihydroequilenin 17α-Dihydroequilin 17α-Epiestriol (16α-hydroxy-17α-estradiol) 17α-Ethynyl-3α-androstanediol 17α-Ethynyl-3β-androstanediol 17β-Dihydroequilenin 17β-Dihydroequilin 17β-Methyl-17α-dihydroequilenin Abiraterone Abiraterone acetate Alestramustine Almestrone Anabolic steroids (e.g.,testosterone andesters ,methyltestosterone ,metandienone (methandrostenolone) ,nandrolone andesters , many others; via estrogenic metabolites)Atrimustine Bolandiol Bolandiol dipropionate Butolame Clomestrone Cloxestradiol Conjugated estriol Conjugated estrogens Cyclodiol Cyclotriol DHEA DHEA-S ent -EstradiolEpiestriol (16β-epiestriol, 16β-hydroxy-17β-estradiol) Epimestrol Equilenin Equilin ERA-63 (ORG-37663) Esterified estrogens Estetrol Estradiol Estramustine Estramustine phosphate Estrapronicate Estrazinol Estriol Estrofurate Estrogenic substances Estromustine Estrone Etamestrol (eptamestrol) Ethinylandrostenediol Ethinylestradiol Ethinylestriol Ethylestradiol Etynodiol Etynodiol diacetate Hexolame Hippulin Hydroxyestrone diacetate Lynestrenol Lynestrenol phenylpropionate Mestranol Methylestradiol Moxestrol Mytatrienediol Nilestriol Norethisterone Noretynodrel Orestrate Pentolame Prodiame Prolame Promestriene RU-16117 Quinestradol Quinestrol Tibolone Xenoestrogens: Anise -related (e.g.,anethole ,anol ,dianethole ,dianol ,photoanethole )Chalconoids (e.g.,isoliquiritigenin ,phloretin ,phlorizin (phloridzin) ,wedelolactone )Coumestans (e.g.,coumestrol ,psoralidin )Flavonoids (incl.7,8-DHF ,8-prenylnaringenin ,apigenin ,baicalein ,baicalin ,biochanin A ,calycosin ,catechin ,daidzein ,daidzin ,ECG ,EGCG ,epicatechin ,equol ,formononetin ,glabrene ,glabridin ,genistein ,genistin ,glycitein ,kaempferol ,liquiritigenin ,mirificin ,myricetin ,naringenin ,penduletin ,pinocembrin ,prunetin ,puerarin ,quercetin ,tectoridin ,tectorigenin )Lavender oil Lignans (e.g.,enterodiol ,enterolactone ,nyasol (cis -hinokiresinol) )Metalloestrogens (e.g.,cadmium )Pesticides (e.g.,alternariol ,dieldrin ,endosulfan ,fenarimol ,HPTE ,methiocarb ,methoxychlor ,triclocarban ,triclosan )Phytosteroids (e.g.,digitoxin (digitalis ),diosgenin ,guggulsterone )Phytosterols (e.g.,β-sitosterol ,campesterol ,stigmasterol )Resorcylic acid lactones (e.g.,zearalanone ,α-zearalenol ,β-zearalenol ,zearalenone ,zeranol (α-zearalanol) ,taleranol (teranol, β-zearalanol) )Steroid -like (e.g.,deoxymiroestrol ,miroestrol )Stilbenoids (e.g.,resveratrol ,rhaponticin )Synthetic xenoestrogens (e.g.,alkylphenols ,bisphenols (e.g.,BPA ,BPF ,BPS ),DDT ,parabens ,PBBs ,PHBA ,phthalates ,PCBs )Others (e.g.,agnuside ,rotundifuran ) MixedSERMs Tooltip Selective estrogen receptor modulators ) Antagonists Coregulator-binding modulators: ERX-11
GPER Tooltip G protein-coupled estrogen receptor
Agonists Antagonists Unknown
Alcohols Barbiturates Benzodiazepines Carbamates Flavonoids Imidazoles Kava constituentsMonoureides Neuroactive steroids Nonbenzodiazepines Phenols Piperidinediones Pyrazolopyridines Quinazolinones Volatiles /gases Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g.,ivermectin )Bromide compounds (e.g.,lithium bromide ,potassium bromide ,sodium bromide )Carbamazepine Chloralose Chlormezanone Clomethiazole Darigabat DEABL Deuterated etifoxine Dihydroergolines (e.g.,dihydroergocryptine ,dihydroergosine ,dihydroergotamine ,ergoloid (dihydroergotoxine) )DS2 Efavirenz Etazepine Etifoxine Fenamates (e.g.,flufenamic acid ,mefenamic acid ,niflumic acid ,tolfenamic acid )Fluoxetine Flupirtine Hopantenic acid KRM-II-81 Lanthanum Lavender oil Lignans (e.g.,4-O-methylhonokiol ,honokiol ,magnolol ,obovatol )Loreclezole Menthyl isovalerate (validolum) Monastrol Nicotinic acid Nicotinamide Org 25,435 Phenytoin Propanidid Retigabine (ezogabine) Safranal Seproxetine Stiripentol Sulfonylalkanes (e.g.,sulfonmethane (sulfonal) ,tetronal ,trional )Terpenoids (e.g.,borneol )Topiramate Valerian constituents (e.g.,isovaleric acid ,isovaleramide ,valerenic acid ,valerenol )
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Group I
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Group II
mGluR2 Tooltip Metabotropic glutamate receptor 2 mGluR3 Tooltip Metabotropic glutamate receptor 3
Group III
mGluR4 Tooltip Metabotropic glutamate receptor 4 mGluR6 Tooltip Metabotropic glutamate receptor 6 mGluR7 Tooltip Metabotropic glutamate receptor 7 mGluR8 Tooltip Metabotropic glutamate receptor 8
PR Tooltip Progesterone receptor
Agonists Testosterone derivatives: Progestins:6,6-Difluoronorethisterone 6,6-Difluoronorethisterone acetate 17α-Allyl-19-nortestosterone Allylestrenol Altrenogest Chloroethynylnorgestrel Cingestol Danazol Desogestrel Dienogest Ethinylandrostenediol Ethisterone Ethynerone Etonogestrel Etynodiol Etynodiol diacetate Gestodene Gestrinone Levonorgestrel Levonorgestrel esters (e.g.,levonorgestrel butanoate )Lynestrenol Lynestrenol phenylpropionate Metynodiol Metynodiol diacetate Norelgestromin Norethisterone (norethindrone) Norethisterone esters (e.g.,norethisterone acetate ,norethisterone enanthate )Noretynodrel Norgesterone Norgestimate Norgestrel Norgestrienone Norvinisterone Oxendolone Quingestanol Quingestanol acetate Tibolone Tigestol Tosagestin ; Anabolic–androgenic steroids:11β-Methyl-19-nortestosterone 11β-Methyl-19-nortestosterone dodecylcarbonate 19-Nor-5-androstenediol 19-Nor-5-androstenedione 19-Nordehydroepiandrosterone Bolandiol Bolandiol dipropionate Bolandione Dimethisterone Dienedione Dienolone Dimethandrolone Dimethandrolone buciclate Dimethandrolone dodecylcarbonate Dimethandrolone undecanoate Dimethyldienolone Dimethyltrienolone Ethyldienolone Ethylestrenol (ethylnandrol) Methyldienolone Metribolone (R-1881) Methoxydienone (methoxygonadiene) Mibolerone Nandrolone Nandrolone esters (e.g.,nandrolone decanoate ,nandrolone phenylpropionate )Norethandrolone Normethandrone (methylestrenolone, normethandrolone, normethisterone) RU-2309 Tetrahydrogestrinone Trenbolone (trienolone) Trenbolone esters (e.g.,trenbolone acetate ,trenbolone enanthate )Trendione Trestolone Trestolone acetate MixedSPRMs Tooltip Selective progesterone receptor modulators ) Antagonists
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