Apigenin
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Basic Info
| Common Name | Apigenin(F05584) |
| 2D Structure | |
| Description | Apigenin 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, 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 and the increase in hINV promoter activity. 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. (A7924). 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. (A7925). 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. (A7926). |
| FRCD ID | F05584 |
| CAS Number | 520-36-5 |
| PubChem CID | 5280443 |
| Formula | C15H10O5 |
| IUPAC Name | 5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one |
| InChI Key | KZNIFHPLKGYRTM-UHFFFAOYSA-N |
| InChI | 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 |
| Canonical SMILES | C1=CC(=CC=C1C2=CC(=O)C3=C(C=C(C=C3O2)O)O)O |
| Isomeric SMILES | C1=CC(=CC=C1C2=CC(=O)C3=C(C=C(C=C3O2)O)O)O |
| Wikipedia | Apigenin |
| Synonyms |
5,7-Dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one
apigenin
520-36-5
Chamomile
Spigenin
Versulin
Apigenol
4',5,7-Trihydroxyflavone
Apigenine
C.I. Natural Yellow 1
|
| Classifies |
Plant Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Phenylpropanoids and polyketides |
| Class | Flavonoids |
| Subclass | Flavones |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Flavones |
| Alternative Parents |
|
| Molecular Framework | Aromatic heteropolycyclic compounds |
| 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 |
| Description | This compound 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). |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 270.24 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 1 |
| Complexity | 411 |
| Monoisotopic Mass | 270.053 |
| Exact Mass | 270.053 |
| XLogP | 1.7 |
| Formal Charge | 0 |
| Heavy Atom Count | 20 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.6364 |
| Human Intestinal Absorption | HIA+ | 0.9887 |
| Caco-2 Permeability | Caco2+ | 0.8541 |
| P-glycoprotein Substrate | Non-substrate | 0.5073 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9543 |
| Non-inhibitor | 0.7525 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.9037 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.6655 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7813 |
| CYP450 2D6 Substrate | Non-substrate | 0.9126 |
| CYP450 3A4 Substrate | Non-substrate | 0.6907 |
| CYP450 1A2 Inhibitor | Inhibitor | 0.9222 |
| CYP450 2C9 Inhibitor | Inhibitor | 0.7746 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9231 |
| CYP450 2C19 Inhibitor | Inhibitor | 0.7043 |
| CYP450 3A4 Inhibitor | Inhibitor | 0.9580 |
| CYP Inhibitory Promiscuity | High CYP Inhibitory Promiscuity | 0.7316 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9559 |
| Non-inhibitor | 0.9098 | |
| AMES Toxicity | Non AMES toxic | 0.8906 |
| Carcinogens | Non-carcinogens | 0.9181 |
| Fish Toxicity | High FHMT | 0.8694 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9394 |
| Honey Bee Toxicity | High HBT | 0.7348 |
| Biodegradation | Not ready biodegradable | 0.8384 |
| Acute Oral Toxicity | III | 0.7012 |
| Carcinogenicity (Three-class) | Non-required | 0.6044 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -2.7765 | LogS |
| Caco-2 Permeability | 0.8904 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.6983 | LD50, mol/kg |
| Fish Toxicity | 0.8038 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.3341 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Homoisoflavonoids Are Potent Glucose Transporter 2 (GLUT2) Inhibitors: APotential Mechanism for the Glucose-Lowering Properties of Polygonatum odoratum. | J Agric Food Chem | 2018 Mar 28 | 29533635 |
| Genoprotective, antioxidant, antifungal and anti-inflammatory evaluation ofhydroalcoholic extract of wild-growing Juniperus communis L. (Cupressaceae)native to Romanian southern sub-Carpathian hills. | BMC Complement Altern Med | 2018 Jan 4 | 29301523 |
| Antioxidant, anti-inflammatory, and enzyme inhibitory activity of natural plant flavonoids and their synthesized derivatives. | J Biochem Mol Toxicol | 2018 Jan | 28972678 |
| Phenolic components and assessment of biological properties of Tchihatchewiaisatidea Boiss. extracts: Docking and functional approaches for designing novelproducts. | Food Chem Toxicol | 2018 Jan | 29198858 |
| Biological effects and chemical characterization of Iris schachtii Markgr.extracts: A new source of bioactive constituents. | Food Chem Toxicol | 2018 Feb | 28797651 |
| Analysis of proautophagic activities of Citrus flavonoids in liver cells reveals the superiority of a natural polyphenol mixture over pure flavones. | J Nutr Biochem | 2018 Aug | 29890411 |
| Dietary Flavonoids and Acarbose Synergistically Inhibit α-Glucosidase and LowerPostprandial Blood Glucose. | J Agric Food Chem | 2017 Sep 27 | 28875706 |
| Apigenin attenuates patulin-induced apoptosis in HEK293 cells by modulatingROS-mediated mitochondrial dysfunction and caspase signal pathway. | Toxicon | 2017 Oct | 28734981 |
| Complementary cereals and legumes for health: Synergistic interaction of sorghum flavones and cowpea flavonols against LPS-induced inflammation in colonic myofibroblasts. | Mol Nutr Food Res | 2017 Jul | 28155259 |
| Activation of TRPV4 by dietary apigenin antagonizes renal fibrosis indeoxycorticosterone acetate (DOCA)-salt-induced hypertension. | Clin Sci (Lond) | 2017 Apr 1 | 28143892 |
| Inhibitory Mechanism of Apigenin on α-Glucosidase and Synergy Analysis ofFlavonoids. | J Agric Food Chem | 2016 Sep 21 | 27581205 |
| Phytoestrogens in milk: Overestimations caused by contamination of the hydrolytic enzyme used during sample extraction. | J Dairy Sci | 2016 Sep | 27394955 |
| Total synthesis of 8-(6″-umbelliferyl)-apigenin and its analogs as anti-diabetic reagents. | Eur J Med Chem | 2016 Oct 21 | 27448923 |
| Food Polyphenol Apigenin Inhibits the Cytochrome P450 Monoxygenase Branch of the Arachidonic Acid Cascade. | J Agric Food Chem | 2016 Nov 30 | 27933871 |
| Natural product HTP screening for antibacterial (E.coli 0157:H7) and anti-inflammatory agents in (LPS from E. coli O111:B4) activated macrophages and microglial cells; focus on sepsis. | BMC Complement Altern Med | 2016 Nov 15 | 27846826 |
| Anti-oxidative assays as markers for anti-inflammatory activity of flavonoids. | Int Immunopharmacol | 2016 Nov | 27598863 |
| Apigetrin from Scutellaria baicalensis Georgi Inhibits Neuroinflammation in BV-2 Microglia and Exerts Neuroprotective Effect in HT22 Hippocampal Cells. | J Med Food | 2016 Nov | 27845861 |
| Protective Role of Flavonoids and Lipophilic Compounds from Jatropha platyphylla on the Suppression of Lipopolysaccharide (LPS)-Induced Inflammation in Macrophage Cells. | J Agric Food Chem | 2016 Mar 9 | 26872073 |
| Apigenin reverses depression-like behavior induced by chronic corticosteronetreatment in mice. | Eur J Pharmacol | 2016 Mar 5 | 26826594 |
| Dietary Apigenin Exerts Immune-Regulatory Activity in Vivo by Reducing NF-κB Activity, Halting Leukocyte Infiltration and Restoring Normal Metabolic Function. | Int J Mol Sci | 2016 Mar 1 | 26938530 |
Targets
- General Function:
- Atp binding
- Specific Function:
- Involved in DNA damage response. Involved in a RAD9A-related damage checkpoint, a pathway that is important in determining whether DNA damage is compatible with cell survival or whether it requires cell elimination by apoptosis. Modulates the RAD9A interaction with BCL2 and thereby induces DNA damages-induced apoptosis.
- Gene Name:
- ATAD5
- Uniprot ID:
- Q96QE3
- Molecular Weight:
- 207568.185 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Transcription regulatory region dna binding
- Specific Function:
- Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.
- Gene Name:
- AHR
- Uniprot ID:
- P35869
- Molecular Weight:
- 96146.705 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Ubiquitin protein ligase binding
- Specific Function:
- Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.
- Gene Name:
- HIF1A
- Uniprot ID:
- Q16665
- Molecular Weight:
- 92669.595 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Oxygen binding
- Specific Function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, retinoid and xenobiotics. Preferentially oxidizes 17beta-estradiol to the carcinogenic 4-hydroxy derivative, and a variety of procarcinogenic compounds to their activated forms, including polycyclic aromatic hydrocarbons. Promotes angiogenesis by removing cellular oxygenation products, thereby decreasing oxidative stress, release of antiangiogenic factor THBS2, then allowing endothelial cells migration, cell adhesion and capillary morphogenesis. These changes are concommitant with the endothelial nitric oxide synthase activity and nitric oxide synthesis. Plays an important role in the regulation of perivascular cell proliferation, migration, and survival through modulation of the intracellular oxidative state and NF-kappa-B expression and/or activity, during angiogenesis. Contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression.
- Gene Name:
- CYP1B1
- Uniprot ID:
- Q16678
- Molecular Weight:
- 60845.33 Da
References
- Shimada T, Tanaka K, Takenaka S, Murayama N, Martin MV, Foroozesh MK, Yamazaki H, Guengerich FP, Komori M: Structure-function relationships of inhibition of human cytochromes P450 1A1, 1A2, 1B1, 2C9, and 3A4 by 33 flavonoid derivatives. Chem Res Toxicol. 2010 Dec 20;23(12):1921-35. doi: 10.1021/tx100286d. [21053930 ]
- General Function:
- Vitamin d 24-hydroxylase activity
- Specific Function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
- Gene Name:
- CYP1A1
- Uniprot ID:
- P04798
- Molecular Weight:
- 58164.815 Da
References
- Allen SW, Mueller L, Williams SN, Quattrochi LC, Raucy J: The use of a high-volume screening procedure to assess the effects of dietary flavonoids on human cyp1a1 expression. Drug Metab Dispos. 2001 Aug;29(8):1074-9. [11454723 ]
- General Function:
- Zinc ion binding
- Specific Function:
- The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.Isoform A: inactive in stimulating c-Src/MAPK signaling on hormone stimulation.Isoform 4: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.
- Gene Name:
- PGR
- Uniprot ID:
- P06401
- Molecular Weight:
- 98979.96 Da
References
- Scippo ML, Argiris C, Van De Weerdt C, Muller M, Willemsen P, Martial J, Maghuin-Rogister G: Recombinant human estrogen, androgen and progesterone receptors for detection of potential endocrine disruptors. Anal Bioanal Chem. 2004 Feb;378(3):664-9. Epub 2003 Oct 25. [14579009 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
- Gene Name:
- ESR1
- Uniprot ID:
- P03372
- Molecular Weight:
- 66215.45 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
- Gene Name:
- ESR2
- Uniprot ID:
- Q92731
- Molecular Weight:
- 59215.765 Da
References
- Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der Burg B, Gustafsson JA: Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology. 1998 Oct;139(10):4252-63. [9751507 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (By similarity).
- Gene Name:
- PPARG
- Uniprot ID:
- P37231
- Molecular Weight:
- 57619.58 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]