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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2006-05-22 14:17:37 UTC
Update Date2020-02-26 21:23:50 UTC
HMDB IDHMDB0002124
Secondary Accession Numbers
  • HMDB02124
Metabolite Identification
Common NameApigenin
DescriptionApigenin is a plant-derived flavonoid that has significant promise as a skin cancer chemopreventive agent. Apigenin inhibits the expression of involucrin (hINV), a marker of keratinocyte differentiation, is increased by differentiating agents via a protein kinase Cdelta (PKCdelta), Ras, MEKK1, and MEK3 cascade that increases AP1 factor level and AP1 factor binding to DNA elements in the hINV promoter. Apigenin suppresses the 12-O-tetradeconylphorbol-13-acetate-dependent increase in AP1 factor expression and binding to the hINV promoter. Apigenin also inhibits the increase in promoter activity observed following overexpression of PKCdelta, constitutively active Ras, or MEKK1. The suppression of PKCdelta activity is associated with reduced phosphorylation of PKCdelta-Y311. Activation of hINV promoter activity by the green tea polyphenol, (-)-epigellocathecin-3-gallate, is also inhibited by apigenin, suggesting that the two chemopreventive agents can produce opposing actions in keratinocytes (PMID: 16982614 ). Apigenin, a flavone abundantly found in fruits and vegetables, exhibits antiproliferative, anti-inflammatory, and antimetastatic activities through poorly defined mechanisms. This flavonoid provides selective activity to promote caspase-dependent-apoptosis of leukemia cells and uncover an essential role of PKCdelta during the induction of apoptosis by apigenin (PMID: 16844095 ). Apigenin markedly induces the expression of death receptor 5 (DR5) and synergistically acts with exogenous soluble recombinant human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to induce apoptosis in malignant tumor cells. On the other hand, apigenin-mediated induction of DR5 expression is not observed in normal human peripheral blood mononuclear cells. Moreover, apigenin does not sensitize normal human peripheral blood mononuclear cells to TRAIL-induced apoptosis (PMID: 16648565 ).
Structure
Data?1582752230
Synonyms
ValueSource
2-(p-Hydroxyphenyl)-5,7-dihydroxychromoneChEBI
4',5,7-TrihydroxyflavoneChEBI
5,7,4'-TrihydroxyflavoneChEBI
5,7-Dihydroxy-2-(4-hydroxyphenyl)-4-benzopyroneChEBI
5,7-Dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-oneChEBI
C.I. natural yellow 1ChEBI
ChamomileChEBI
SpigeninChEBI
VersulinChEBI
4',5,7-Trihydroxy-flavoneHMDB
4,5, 7-TrihydroxyflavoneHMDB
5,7-Dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-oneHMDB
ApigenolHMDB
Chemical FormulaC15H10O5
Average Molecular Weight270.2369
Monoisotopic Molecular Weight270.05282343
IUPAC Name5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one
Traditional Namechamomile
CAS Registry Number520-36-5
SMILES
OC1=CC=C(C=C1)C1=CC(=O)C2=C(O)C=C(O)C=C2O1
InChI Identifier
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
InChI KeyKZNIFHPLKGYRTM-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as flavones. These are flavonoids with a structure based on the backbone of 2-phenylchromen-4-one (2-phenyl-1-benzopyran-4-one).
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassFlavonoids
Sub ClassFlavones
Direct ParentFlavones
Alternative Parents
Substituents
  • 4'-hydroxyflavonoid
  • 5-hydroxyflavonoid
  • 7-hydroxyflavonoid
  • Flavone
  • Hydroxyflavonoid
  • Chromone
  • Benzopyran
  • 1-benzopyran
  • 1-hydroxy-4-unsubstituted benzenoid
  • 1-hydroxy-2-unsubstituted benzenoid
  • Phenol
  • Pyranone
  • Monocyclic benzene moiety
  • Benzenoid
  • Pyran
  • Vinylogous acid
  • Heteroaromatic compound
  • Organoheterocyclic compound
  • Oxacycle
  • Organic oxygen compound
  • Organooxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Route of exposure:

Source:

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point347.5 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogP3.02PERRISSOUD,D & TESTA,B (1986)
Predicted Properties
PropertyValueSource
Water Solubility0.12 g/LALOGPS
logP3.07ALOGPS
logP2.71ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)6.63ChemAxon
pKa (Strongest Basic)-5.2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area86.99 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity72.91 m³·mol⁻¹ChemAxon
Polarizability26.78 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-00di-0000900000-b6d7fc88c039e719d164Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00di-0433900000-b411d851fccc9f228d84Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-03xv-1913500000-be46740b1210f9e106eeSpectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-00di-0000900000-b6d7fc88c039e719d164Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00fu-0390000000-746c7fa7b11e53e27235Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positivesplash10-0229-4222900000-fe657c625506c272a036Spectrum
LC-MS/MSLC-MS/MS Spectrum - ESI-TOF 30V, Negativesplash10-014i-0940000000-eb8b08c7beca627dc728Spectrum
LC-MS/MSLC-MS/MS Spectrum - ESI-TOF , Negativesplash10-014i-0090000000-3fea3046af52ea21ae28Spectrum
LC-MS/MSLC-MS/MS Spectrum - ESI-TOF 30V, Negativesplash10-014i-0940000000-eb8b08c7beca627dc728Spectrum
LC-MS/MSLC-MS/MS Spectrum - ESI-TOF , Negativesplash10-014i-0090000000-3fea3046af52ea21ae28Spectrum
LC-MS/MSLC-MS/MS Spectrum - DI-ESI-qTof , Negativesplash10-014i-0890000000-c8366acac0c0d42ae2e8Spectrum
LC-MS/MSLC-MS/MS Spectrum - DI-ESI-qTof , Positivesplash10-0udi-0920000000-812a3ee12823ec0b2025Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-003r-0194000200-b2908d4b21e6769c5a08Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00di-3970000000-5a23944b045cfe1763b1Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0090000000-0f608530bf761944dbf3Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0090000000-0c659ac43b543480168bSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0690000000-e19eed49b8311d9cd339Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0910000000-57a56bfe2cce55357a11Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0900000000-b8799a618cff0ac84ddbSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0490000000-f9a416c79166c84ca773Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0900000000-1499c7f2bceeb3e13f52Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0490000000-413a7da79773bc92a112Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0090000000-8f4d30104539ae85cd50Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0290000000-32e8793c17b364eee127Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-0uea-0900000000-52147353f7af35162dabSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0090000000-7c7c531f383cbaad5b23Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-0090000000-bb93867833cf83cbdb01Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-7890000000-ef384ab54a966e53fb23Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0090000000-31e5cabfee91b72de296Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-0090000000-12d2a0ddf52acf6dc93aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0gdi-3960000000-847553cbcf5b653a9059Spectrum
Biological Properties
Cellular Locations
  • Membrane (predicted from logP)
Biospecimen Locations
  • Blood
  • Feces
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.0106 +/- 0.0123 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.0119 +/- 0.0126 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.127 +/- 0.081 uMAdult (>18 years old)BothNormal details
FecesDetected but not Quantified Adult (>18 years old)Both
Normal
details
FecesDetected but not Quantified Adult (>18 years old)Both
Normal
details
FecesDetected but not Quantified Adult (>18 years old)Both
Normal
details
UrineDetected and Quantified0.000222 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified0.00533 umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified0.0110 +/- 0.0210 umol/mmol creatinineAdult (>18 years old)Both
Normal
details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
FecesDetected but not Quantified Adult (>18 years old)Both
Colorectal cancer
details
Associated Disorders and Diseases
Disease References
Colorectal cancer
  1. Goedert JJ, Sampson JN, Moore SC, Xiao Q, Xiong X, Hayes RB, Ahn J, Shi J, Sinha R: Fecal metabolomics: assay performance and association with colorectal cancer. Carcinogenesis. 2014 Sep;35(9):2089-96. doi: 10.1093/carcin/bgu131. Epub 2014 Jul 18. [PubMed:25037050 ]
Associated OMIM IDs
DrugBank IDDB07352
Phenol Explorer Compound ID228
FooDB IDFDB002798
KNApSAcK IDC00003817
Chemspider ID4444100
KEGG Compound IDC01477
BioCyc IDCPD-431
BiGG IDNot Available
Wikipedia LinkApigenin
METLIN ID3397
PubChem Compound5280443
PDB IDNot Available
ChEBI ID18388
Food Biomarker OntologyNot Available
VMH IDNot Available
References
Synthesis ReferenceChen, Xin; Li, Ping. Processes for the preparation of apigenin from naringin via rhoifolin or naringenin intermediate. Faming Zhuanli Shenqing Gongkai Shuomingshu (2005), 9 pp
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Balasubramanian S, Zhu L, Eckert RL: Apigenin inhibition of involucrin gene expression is associated with a specific reduction in phosphorylation of protein kinase Cdelta Tyr311. J Biol Chem. 2006 Nov 24;281(47):36162-72. Epub 2006 Sep 18. [PubMed:16982614 ]
  2. Vargo MA, Voss OH, Poustka F, Cardounel AJ, Grotewold E, Doseff AI: Apigenin-induced-apoptosis is mediated by the activation of PKCdelta and caspases in leukemia cells. Biochem Pharmacol. 2006 Sep 14;72(6):681-92. Epub 2006 Jul 17. [PubMed:16844095 ]
  3. Horinaka M, Yoshida T, Shiraishi T, Nakata S, Wakada M, Sakai T: The dietary flavonoid apigenin sensitizes malignant tumor cells to tumor necrosis factor-related apoptosis-inducing ligand. Mol Cancer Ther. 2006 Apr;5(4):945-51. [PubMed:16648565 ]

Enzymes

General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naphthol, paranitrophenol, scopoletin, and umbelliferone.
Gene Name:
UGT1A1
Uniprot ID:
P22309
Molecular weight:
59590.91
Reactions
Apigenin → 3,4,5-trihydroxy-6-{[5-hydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-7-yl]oxy}oxane-2-carboxylic aciddetails
Apigenin → 3,4,5-trihydroxy-6-{[7-hydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-5-yl]oxy}oxane-2-carboxylic aciddetails
Apigenin → 6-[4-(5,7-dihydroxy-4-oxo-4H-chromen-2-yl)phenoxy]-3,4,5-trihydroxyoxane-2-carboxylic aciddetails