ELLAGIC ACID

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H6O8
Molecular Weight	302.1926
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1=C(O)C2=C3C(=C1)C(=O)OC4=C3C(=CC(O)=C4O)C(=O)O2

InChI

InChIKey=AFSDNFLWKVMVRB-UHFFFAOYSA-N

InChI=1S/C14H6O8/c15-5-1-3-7-8-4(14(20)22-11(7)9(5)17)2-6(16)10(18)12(8)21-13(3)19/h1-2,15-18H

HIDE SMILES / InChI

Description
Sources: https://www.drugbank.ca/drugs/DB08846
Curator's Comment: Ellagic acid is a dilactone of hexahydroxydiphenic acid, that found in numerous fruits and vegetables. Ellagic acid was first discovered by chemist Henri Braconnot in 1831. Ellagic acid is found in oaks species like the North American white oak (Quercus alba) and European red oak (Quercus robur). The highest levels of ellagic acid are found in walnuts, pecans, cranberries, raspberries, strawberries, and grapes, as well as distilled beverages. It is also found in peach, and other plant foods. Ellagic acid has antiproliferative and antioxidant properties in a number of in vitro and small-animal models. The antiproliferative properties of ellagic acid may be due to its ability to directly inhibit the DNA binding of certain carcinogens, including nitrosamines and polycyclic aromatic hydrocarbons. As with other polyphenol antioxidants, ellagic acid has a chemoprotective effect in cellular models by reducing oxidative stress. Ellagic acid is an investigational drug studied for treatment of Follicular Lymphoma (phase 2 trial), protection from brain injury of intrauterine growth restricted babies (phase 1 and 2 trial), improvement of cardiovascular function in adolescents who are obese (phase 2 trial), and topical treatment of solar lentigines. Ellagic acid has been marketed as a dietary supplement with a range of claimed benefits against cancer, heart disease, and other medical problems. Ellagic acid has been identified by the U.S. Food and Drug Administration as a "fake cancer 'cure' consumers should avoid".

Ellagic acid is a dilactone of hexahydroxydiphenic acid, that found in numerous fruits and vegetables. Ellagic acid was first discovered by chemist Henri Braconnot in 1831. Ellagic acid is found in oaks species like the North American white oak (Quercus alba) and European red oak (Quercus robur). The highest levels of ellagic acid are found in walnuts, pecans, cranberries, raspberries, strawberries, and grapes, as well as distilled beverages. It is also found in peach, and other plant foods. Ellagic acid has antiproliferative and antioxidant properties in a number of in vitro and small-animal models. The antiproliferative properties of ellagic acid may be due to its ability to directly inhibit the DNA binding of certain carcinogens, including nitrosamines and polycyclic aromatic hydrocarbons. As with other polyphenol antioxidants, ellagic acid has a chemoprotective effect in cellular models by reducing oxidative stress. Ellagic acid is an investigational drug studied for treatment of Follicular Lymphoma (phase 2 trial), protection from brain injury of intrauterine growth restricted babies (phase 1 and 2 trial), improvement of cardiovascular function in adolescents who are obese (phase 2 trial), and topical treatment of solar lentigines. Ellagic acid has been marketed as a dietary supplement with a range of claimed benefits against cancer, heart disease, and other medical problems. Ellagic acid has been identified by the U.S. Food and Drug Administration as a "fake cancer 'cure' consumers should avoid".

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Casein kinase II alpha 3 Target ID: CHEMBL3629 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19414254	Inhibitor 8228	40.0 nM [IC50]
Aldose reductase 44 Target ID: CHEMBL1900 Sources: http://www.ncbi.nlm.nih.gov/pubmed/22377675	Inhibitor 8228	200.0 nM [IC50]
Tyrosine-protein kinase TIE-2 6 Target ID: CHEMBL4128 Sources: http://www.ncbi.nlm.nih.gov/pubmed/22377675	Inhibitor 8228	260.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Follicular lymphoma 3 Sources: https://clinicaltrials.gov/ct2/show/NCT00455416	Primary		Phase II 1144	Unknown Approved Use Unknown
HPV infection 1 Sources: https://clinicaltrials.gov/ct2/show/NCT02263378	Primary		Not Provided 503	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
3.25 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16172180	13.5 mg 1 times / day multiple, oral dose: 13.5 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ELLAGIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
200.2 ng/mL EXPERIMENT https://scialert.net/abstract/?doi=pjn.2009.1661.1664	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		ELLAGIC ACID serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
17.61 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16172180	13.5 mg 1 times / day multiple, oral dose: 13.5 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ELLAGIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1041.8 ng × h/mL EXPERIMENT https://scialert.net/abstract/?doi=pjn.2009.1661.1664	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		ELLAGIC ACID serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.57 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16172180	13.5 mg 1 times / day multiple, oral dose: 13.5 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ELLAGIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
8.4 h EXPERIMENT https://scialert.net/abstract/?doi=pjn.2009.1661.1664	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		ELLAGIC ACID serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
50% EXPERIMENT https://scialert.net/abstract/?doi=pjn.2009.1661.1664	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		ELLAGIC ACID serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2E1 876 CYP1A1 110 CYP2B1 14 CYP3A1/2 1 OAT1 595 OAT4 145 P-gp 1437 BCRP 691		CYP1A1 109 UGT1A10 9

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
BCRP 765	inhibitor 3240 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476959/	no
CYP3A1/2 4	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/8625497/ Page: 1.0	no
P-gp 1626	inhibitor 3240 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476959/; https://www.degruyter.com/document/doi/10.1515/dmpt-2018-0020/html	no	yes (co-administration study) Comment: The increase in Cmax, AUC, AUMC, AUCtotal and t1/2 of linagliptin was found to be 2.0-fold, 1.2-fold, 1.74- fold, 1.52-fold and 0.5-fold, respectively, in the EA pretreated group compared with the control group. In vitro experiments showed no inhibition Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476959/; https://www.degruyter.com/document/doi/10.1515/dmpt-2018-0020/html
OAT4 145	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/15870380/ Page: 3.0	weak [Inhibition 35 uM]
OAT1 599	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/15870380/ Page: 3.0	yes [IC50 0.207 uM]
CYP1A1 218	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/8625497/ Page: 1.0	yes [Inhibition 100 uM]
CYP2B1 41	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/8625497/ Page: 1.0	yes [Inhibition 100 uM]
CYP2E1 964	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/8625497/ Page: 1.0	yes [Inhibition 100 uM]
CYP1A1 218	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/19469472/	yes
UGT1A10 41	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/19469472/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4775	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4775
ChemicalBook	CB6214708	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6214708
MolPort	MolPort-000-861-050	https://www.molport.com/shop/molecule-link/MolPort-000-861-050
Selleck Chemicals	Ellagic-acid	http://www.selleckchem.com/products/Ellagic-acid.html
ZINC	ZINC000003872446	http://zinc15.docking.org/substances/ZINC000003872446
eMolecules	509332	https://www.emolecules.com/cgi-bin/more?vid=509332

PubMed

Title	Date	PubMed
Steroid hormone activity of flavonoids and related compounds.	2000 Jul	10989984
Ellagic acid inhibits nucleoside diphosphate kinase-B activity.	2001	11793995
Ellagic acid inhibited 2-aminofluorene and p-aminobenzoic acid acetylation by mononuclear leucocytes from Sprague-Dawley rats.	2001	11258539
Application of Eudragit P-4135F for the delivery of ellagic acid to the rat lower small intestine.	2001 Aug	11518017
Ellagic [correction of ellagica] acid inhibits arylamine N-acetyltransferase activity and DNA adduct formation in human bladder tumor cell lines (T24 and TSGH 8301).	2001 Dec	11828989
Inhibition of cellular transformation by berry extracts.	2001 Feb	11181460
Mut-Test to detect substances suppressing spontaneous mutation due to oxidative damage.	2001 Jan 25	11152968
IGF-II down regulation associated cell cycle arrest in colon cancer cells exposed to phenolic antioxidant ellagic acid.	2001 Jan-Feb	11299762
Ellagic acid rhamnosides from the stem bark of Eucalyptus globulus.	2001 Jun	11394863
[Screening test on protein C].	2001 Mar	12014076
Use of methanolysis for the determination of total ellagic and gallic acid contents of wood and food products.	2001 Mar	11312829
[Antioxidant properties of novel preparations--bioflavonoid derivatives and tannins].	2001 Mar-Apr	11548450
In vitro antiplasmodial activity of extracts of Tristaniopsis species and identification of the active constituents: ellagic acid and 3,4,5-trimethoxyphenyl-(6'-O-galloyl)-O-beta-D-glucopyranoside.	2001 May	11374952
Unusually large numbers of electrons for the oxidation of polyphenolic antioxidants.	2001 May 3	11325537
Antibacterial action of several tannins against Staphylococcus aureus.	2001 Oct	11581226
Influence of cultivar on quality parameters and chemical composition of strawberry fruits grown in Brazil.	2002 Apr 24	11958626
In vitro antiplasmodial activity of extracts of Alchornea cordifolia and identification of an active constituent: ellagic acid.	2002 Aug	12127243
Inhibition of cancer cell growth by crude extract and the phenolics of Terminalia chebula retz. fruit.	2002 Aug	12127233
Effect of freezing and storage on the phenolics, ellagitannins, flavonoids, and antioxidant capacity of red raspberries.	2002 Aug 28	12188629
DNA-damaging agents from Crypteronia paniculata.	2002 Dec	12502343
Evidence for a global inhibitor-induced conformation change on the Ca(2+)-ATPase of sarcoplasmic reticulum from paired inhibitor studies.	2002 Feb 26	11851435
Effect of ellagic acid on gastric damage induced in ischemic rat stomachs following ammonia or reperfusion.	2002 Jan 25	11848298
One step purification of corilagin and ellagic acid from Phyllanthus urinaria using high-speed countercurrent chromatography.	2002 Jan-Feb	11899601
Ellagic acid and ellagitannins affect on sedimentation in muscadine juice and wine.	2002 Jul 3	12083868
Protection against dextran sulfate sodium-induced colitis by microspheres of ellagic acid in rats.	2002 Jul 5	12074942
Pharmacologically active ellagitannins from Terminalia myriocarpa.	2002 Jun	12094296
Free radical scavengers, anti-inflammatory and analgesic activity of Acaena magellanica.	2002 Jun	12079000
Determination of free and total phenolic acids in plant-derived foods by HPLC with diode-array detection.	2002 Jun 19	12059140
In vitro anti-Neisseria gonorrhoeae activity of Terminalia macroptera leaves.	2002 Jun 4	12076813
Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants.	2002 Mar 1	12002526
A rapid screening assay for antioxidant potential of natural and synthetic agents in vitro.	2002 May	11956593
Alpha-tocopherol decreases superoxide anion release in human monocytes under hyperglycemic conditions via inhibition of protein kinase C-alpha.	2002 Oct	12351446
Ellagic acid derivatives and cytotoxic cucurbitacins from Elaeocarpus mastersii.	2002 Sep	12169311
Effect of naturally occurring plant phenolics on the induction of drug metabolizing enzymes by o-toluidine.	2003 Apr 15	12604171
Stages of activation of hepatic stellate cells: effects of ellagic acid, an inhibiter of liver fibrosis, on their differentiation in culture.	2003 Dec	14710849
Antioxidant activity of Egyptian Eucalyptus camaldulensis var. brevirostris leaf extracts.	2003 Feb	12653437
In vitro studies on the mechanism of action of two compounds with antiplasmodial activity: ellagic acid and 3,4,5-trimethoxyphenyl(6'-O-aalloyl)-beta-D-glucopyranoside.	2003 Feb	12624824
Mechanism-based in vitro screening of potential cancer chemopreventive agents.	2003 Feb-Mar	12628514
Evaluation of the bioavailability and metabolism in the rat of punicalagin, an antioxidant polyphenol from pomegranate juice.	2003 Jan	12594538
Inhibition of metalloproteinase-9 activity and gene expression by polyphenolic compounds isolated from the bark of Tristaniopsis calobuxus (Myrtaceae).	2003 Jul	12943230
Two new ellagic acid rhamnosides from Punica granatum heartwood.	2003 Jul	12898431
Identification of natural dyes in archeological Coptic textiles by liquid chromatography with diode array detection.	2003 Mar 14	12650256
Isolation and synthesis of a new bioactive ellagic acid derivative from Combretum yunnanensis.	2003 May	12762821
Determination of immunological activity in vitro of some plant raw materials.	2003 May-Jun	14556488

Patents

Sample Use Guides

In Vivo Use Guide

The rats were fasted overnight and diabetes was induced by a single dose via intraperitoneal (i.p.) injection of streptozotocin solution (STZ). A total of 32 Wistar Albino rats was used. The rats were randomly divided into four groups, with eight rats each: normal controls (not diabetic), only ellagic acid treated (ellagic acid controls, not diabetic), diabetic control (STZ, diabetic), and ellagic acid treated diabetic (STZ + ellagic acid). The experiment was designed to last a total of 28 days. The dose of the ellagic acid was arranged (50 mg/kg/day orally)

Route of Administration: Oral

In Vitro Use Guide

A total of 2 x 106 cells were seeded in 100 mm plastic dishes and treated with 30mkM Ellagic acid . After 24 h, media was discarded and the cells were washed twice with PBS

Name

Type

Language

ELLAGIC ACID

Official Name

English

ELLAGIC ACID [MI]

Common Name

English

2,3,7,8-TETRAHYDROXY(1)BENZOPYRANO(5,4,3-CDE)-(1)BENZOPYRAN-5,10-DIONE

Systematic Name

English

ellagic acid [INN]

Common Name

English

ELLAGIC ACID [HSDB]

Common Name

English

NSC-407286

Code

English

NSC-656272

Code

English

Ellagic acid [WHO-DD]

Common Name

English

ELLAGIC ACID [INCI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C68538