ELLAGIC ACID

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H6O8
Molecular Weight	302.1932
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

c1c2c3c4c(cc(c(c4oc2=O)O)O)c(=O)oc3c(c1O)O

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 7728	40.0 nM [IC50]
Aldose reductase 43 Target ID: CHEMBL1900 Sources: http://www.ncbi.nlm.nih.gov/pubmed/22377675	Inhibitor 7728	200.0 nM [IC50]
Tyrosine-protein kinase TIE-2 6 Target ID: CHEMBL4128 Sources: http://www.ncbi.nlm.nih.gov/pubmed/22377675	Inhibitor 7728	260.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Follicular lymphoma 3 Sources: https://clinicaltrials.gov/ct2/show/NCT00455416	Primary		Phase II 1101	Unknown Approved Use Unknown
HPV infection 1 Sources: https://clinicaltrials.gov/ct2/show/NCT02263378	Primary		Not Provided 492	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 790 CYP1A1 96 CYP2B1 14 CYP3A1/2 1 OAT1 554 OAT4 131 P-gp 1330 BCRP 643		CYP1A1 98 UGT1A10 9

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
BCRP 713	inhibitor 3045 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476959/	no
CYP3A1/2 4	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/8625497/ Page: 1.0	no
P-gp 1514	inhibitor 3045 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 131	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/15870380/ Page: 3.0	weak [Inhibition 35 uM]
OAT1 558	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/15870380/ Page: 3.0	yes [IC50 0.207 uM]
CYP1A1 192	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/8625497/ Page: 1.0	yes [Inhibition 100 uM]
CYP2B1 38	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/8625497/ Page: 1.0	yes [Inhibition 100 uM]
CYP2E1 871	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/8625497/ Page: 1.0	yes [Inhibition 100 uM]
CYP1A1 192	inducer 1440 Sources: https://pubmed.ncbi.nlm.nih.gov/19469472/	yes
UGT1A10 38	inducer 1440 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
Inhibition of human immunodeficiency viral replication by tannins and related compounds.	1992 May	1416904
[Screening test on protein C].	2001 Mar	12014076
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
Ellagitannins, flavonoids, and other phenolics in red raspberries and their contribution to antioxidant capacity and vasorelaxation properties.	2002 Aug 28	12188628
DNA-damaging agents from Crypteronia paniculata.	2002 Dec	12502343
Fatty acid synthase inhibitors from plants: isolation, structure elucidation, and SAR studies.	2002 Dec	12502337
Two ellagitannins from Punica granatum heartwood.	2002 Dec	12453528
Two new and four known polyphenolics obtained as new cell-cycle inhibitors from Rubus aleaefolius Poir.	2002 Dec	12450251
[Studies on the chemical constituents in the leaves of Cyclocarya paliurus].	2002 Jan	12774356
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
Cytotoxic, hypoglycemic activity and phytochemical analysis of Rubus imperialis (Rosaceae).	2002 Mar-Apr	12064725
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
Effects of DX-9065a, an inhibitor of factor Xa, on ellagic acid-induced plantar skin thrombosis assessed in tetrodotoxin- and N(omega)-nitro-L-arginine-treated rats.	2003 Apr	12719661
Effect of naturally occurring plant phenolics on the induction of drug metabolizing enzymes by o-toluidine.	2003 Apr 15	12604171
DNA damaging activity of ellagic acid derivatives.	2003 Apr 3	12628683
Polyphenols of Melaleuca quinquenervia leaves--pharmacological studies of grandinin.	2003 Aug	12916075
Aldose reductase inhibitors from the nature.	2003 Aug	12871134
Frontal immunoaffinity chromatography with mass spectrometric detection: a method for finding active compounds from traditional Chinese herbs.	2003 Aug 15	14632110
Phenolic content and antioxidant capacity of muscadine grapes.	2003 Aug 27	12926904
Effects of tannins on Chinese hamster cell line B14.	2003 Aug 5	12948821
Antioxidant and pro-oxidant effects of tannins in digestive cells of the freshwater mussel Unio tumidus.	2003 Aug 5	12948811
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
Antiprotozoal activity of the constituents of Rubus coriifolius.	2003 Jun	12820241
Unique phenolic carboxylic acids from Sanguisorba minor.	2003 Jun	12770593
[Cloudberry: an important source of ellagic acid, an anti-oxidant].	2003 Jun 26	12830265
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
Repeated oral administration of high doses of the pomegranate ellagitannin punicalagin to rats for 37 days is not toxic.	2003 May 21	12744688
Determination of immunological activity in vitro of some plant raw materials.	2003 May-Jun	14556488
Induction of rat hepatic and intestinal UDP-glucuronosyltransferases by naturally occurring dietary anticarcinogens.	2003 Oct	12869420
Pharmacokinetic study of ellagic acid in rat after oral administration of pomegranate leaf extract.	2003 Oct 25	14552830
Phenolic compounds and fatty acids from acorns (Quercus spp.), the main dietary constituent of free-ranged Iberian pigs.	2003 Oct 8	14518951
Analysis of ellagitannins and conjugates of ellagic acid and quercetin in raspberry fruits by LC-MSn.	2003 Sep	12943785
Intestinal epithelial cell accumulation of the cancer preventive polyphenol ellagic acid--extensive binding to protein and DNA.	2003 Sep 15	12963477
Antioxidative capacity of extracts and constituents in Cornus capitata adventitious roots.	2003 Sep 24	13129293
Antimicrobial activity of Rubus chamaemorus leaves.	2004 Jan	14693229

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