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 8297	40.0 nM [IC50]
Aldose reductase 44 Target ID: CHEMBL1900 Sources: http://www.ncbi.nlm.nih.gov/pubmed/22377675	Inhibitor 8297	200.0 nM [IC50]
Tyrosine-protein kinase TIE-2 6 Target ID: CHEMBL4128 Sources: http://www.ncbi.nlm.nih.gov/pubmed/22377675	Inhibitor 8297	260.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Follicular lymphoma 3 Sources: https://clinicaltrials.gov/ct2/show/NCT00455416	Primary		Phase II 1132	Unknown Approved Use Unknown
HPV infection 1 Sources: https://clinicaltrials.gov/ct2/show/NCT02263378	Primary		Not Provided 504	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 882 CYP1A1 110 CYP2B1 14 CYP3A1/2 1 OAT1 599 OAT4 146 P-gp 1461 BCRP 699		CYP1A1 108 UGT1A10 9

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
BCRP 773	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476959/	no
CYP3A1/2 4	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/8625497/ Page: 1.0	no
P-gp 1650	inhibitor 3277 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 146	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15870380/ Page: 3.0	weak [Inhibition 35 uM]
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15870380/ Page: 3.0	yes [IC50 0.207 uM]
CYP1A1 218	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/8625497/ Page: 1.0	yes [Inhibition 100 uM]
CYP2B1 41	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/8625497/ Page: 1.0	yes [Inhibition 100 uM]
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/8625497/ Page: 1.0	yes [Inhibition 100 uM]
CYP1A1 218	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/19469472/	yes
UGT1A10 41	inducer 1573 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
Effects of lyophilized black raspberries on azoxymethane-induced colon cancer and 8-hydroxy-2'-deoxyguanosine levels in the Fischer 344 rat.	2001	11962247
Less damaging effect of whisky in rat stomachs in comparison with pure ethanol. Role of ellagic acid, the nonalcoholic component.	2001	11842277
Ellagic acid inhibited 2-aminofluorene and p-aminobenzoic acid acetylation by mononuclear leucocytes from Sprague-Dawley rats.	2001	11258539
Ellagic acid formation from galloylglucoses by a crude enzyme of Cornus capitata adventitious roots.	2001 Aug	11577731
Ellagitannins and hexahydroxydiphenoyl esters as inhibitors of vertebrate squalene epoxidase.	2001 Aug	11520216
Application of Eudragit P-4135F for the delivery of ellagic acid to the rat lower small intestine.	2001 Aug	11518017
Inhibitory activity for chitin synthase II from Saccharomyces cerevisiae by tannins and related compounds.	2001 Aug	11509967
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
Modulation of radiation-induced protein kinase C activity by phenolics.	2001 Dec	11787891
Antiproliferative constituents in the plant 8. Seeds of Rhynchosia volubilis.	2001 Dec	11767121
IGF-II down regulation associated cell cycle arrest in colon cancer cells exposed to phenolic antioxidant ellagic acid.	2001 Jan-Feb	11299762
Quinone isomers of the WS-5995 antibiotics: synthetic antitumor agents that inhibit macromolecule synthesis, block nucleoside transport, induce DNA fragmentation, and decrease the growth and viability of L1210 leukemic cells more effectively than ellagic acid and genistein in vitro.	2001 Jun	11395569
Ellagic acid rhamnosides from the stem bark of Eucalyptus globulus.	2001 Jun	11394863
Use of methanolysis for the determination of total ellagic and gallic acid contents of wood and food products.	2001 Mar	11312829
Identification of hydrolysable tannins in the reaction zone of Eucalyptus nitens wood by high performance liquid chromatography--electrospray ionisation mass spectrometry.	2001 Mar-Apr	11705240
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
Cytogenetic effects of propyl gallate in CHO-K1 cells.	2001 Nov 15	11673077
Strong antioxidant activity of ellagic acid in mammalian cells in vitro revealed by the comet assay.	2001 Nov-Dec	11911267
Phenolic compounds from Miconia myriantha inhibiting Candida aspartic proteases.	2001 Oct	11678651
Characterization of peroxidase-mediated chlorophyll bleaching in strawberry fruit.	2001 Oct	11557069
Aldose reductase inhibitors from the fruits of Caesalpinia ferrea Mart.	2001 Sep	11695881
Effect of chemopreventive agents on DNA adduction induced by the potent mammary carcinogen dibenzo[a,l]pyrene in the human breast cells MCF-7.	2001 Sep 1	11506803
Chemoprevention of heterocyclic amine-induced mammary carcinogenesis in rats.	2002	11921198
Phenolic compounds and antioxidant capacity of Georgia-grown blueberries and blackberries.	2002 Apr 10	11929309
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
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
Pharmacologically active ellagitannins from Terminalia myriocarpa.	2002 Jun	12094296
Free radical scavengers, anti-inflammatory and analgesic activity of Acaena magellanica.	2002 Jun	12079000
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
Free radical studies of ellagic acid, a natural phenolic antioxidant.	2002 Mar 27	11902978
Cytotoxic, hypoglycemic activity and phytochemical analysis of Rubus imperialis (Rosaceae).	2002 Mar-Apr	12064725
A rapid screening assay for antioxidant potential of natural and synthetic agents in vitro.	2002 May	11956593
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
Frontal immunoaffinity chromatography with mass spectrometric detection: a method for finding active compounds from traditional Chinese herbs.	2003 Aug 15	14632110
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
Inhibition of metalloproteinase-9 activity and gene expression by polyphenolic compounds isolated from the bark of Tristaniopsis calobuxus (Myrtaceae).	2003 Jul	12943230
Unique phenolic carboxylic acids from Sanguisorba minor.	2003 Jun	12770593
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
Antioxidative capacity of extracts and constituents in Cornus capitata adventitious roots.	2003 Sep 24	13129293

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