Natural Product (NP) Details

General Information of the NP (ID: NP0649)
Name
Ellagic acid
Synonyms
Benzoaric acid; Lagistase; Eleagic acid; Alizarine Yellow; Elagostasine; 2,3,7,8-Tetrahydroxychromeno[5,4,3-cde]chromene-5,10-dione; Ellagic acid dihydrate; Llagic acid; Acide ellagique; Acido elagico; Acidum ellagicum; C.I. 55005; Gallogen (VAN); Gallogen (astringent); C.I. 75270; Ellagate; Ellagic acid [INN:DCF]; UNII-19YRN3ZS9P; Acido elagico [INN-Spanish]; CCRIS 774; Gallogen, astringent; Acide ellagique [INN-French]; Acidum ellagicum [INN-Latin]; MLS000069632; C14H6O8; EINECS 207-508-3; NSC407286; NSC 40728
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Species Origin Lagerstroemia speciosa ...     Click to Show/Hide
Lagerstroemia speciosa
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Myrtales
Family: Lythraceae
Genus: Lagerstroemia
Species: Lagerstroemia speciosa
Toxicodendron succedaneum
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Sapindales
Family: Anacardiaceae
Genus: Toxicodendron
Species: Toxicodendron succedaneum
Rhus chinensis
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Sapindales
Family: Anacardiaceae
Genus: Rhus
Species: Rhus chinensis
Triadica cochinchinensis
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Malpighiales
Family: Euphorbiaceae
Genus: Triadica
Species: Triadica cochinchinensis
Disease Rheumatoid arthritis [ICD-11: FA20] Investigative [1]
Structure
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2D MOL

3D MOL

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Formula
C14H6O8
PubChem CID
5281855
Canonical SMILES
C1=C2C3=C(C(=C1O)O)OC(=O)C4=CC(=C(C(=C43)OC2=O)O)O
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
InChIKey
AFSDNFLWKVMVRB-UHFFFAOYSA-N
CAS Number
CAS 476-66-4
Herb ID
HBIN025006
ETMC ID
2721
SymMap ID
SMIT00090
TCMSP ID
MOL001002
TTD Drug ID
D0A1CM
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Temozolomide      Brain cancer     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CDH1  Molecule Info 
Pathway MAP
Down-regulation Expression CDH2  Molecule Info 
Pathway MAP
Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
                    In-vitro Model C6 CVCL_0194 Rat malignant glioma Rattus norvegicus
                    Experimental
                    Result(s)		 Combining ellagic acid with temozolomide mediates the cadherin switch and angiogenesis in a glioblastoma model.
          Bevacizumab      Colorectal cancer     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression ABCB1  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression MGMT  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model C6 CVCL_0194 Rat malignant glioma Rattus norvegicus
                    Experimental
                    Result(s)		 Antiproliferative efficacy of EA combined with BEV, probably through inhibition of MGMT expression and time-dependent inhibition of MDR1.
          Sorafenib      Renal cell carcinoma     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Activity CASP3  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation ROS generation
Up-regulation Cytochrome c release
                    In-vivo Model Dietylnitrosamine and 2-acetylami nofluorene were used to induce HCC in male Sprague-Dawley rats.
                    Experimental
                    Result(s)		 EA and SOR are effective on the HCC rat model through mitochondria and hepatocytes targeting.
          5-fluorouracil      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
                    In-vitro Model HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
COLO 320DM CVCL_0219 Colon adenocarcinoma Homo sapiens
SW480 CVCL_0546 Colon adenocarcinoma Homo sapiens
LoVo CVCL_0399 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Ellagic acid synergistically potentiated chemosensitivity to 5-fluorouracil in colorectal cancer cells.
          Erlotinib      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model Ba/F3 CVCL_0161 Healthy Mus musculus
WEHI-265.1 CVCL_3620 Mouse leukemia Mus musculus
                    In-vivo Model Ba/F3-insH cell line xenografts were generated by injecting 5*106 cells in 50% matrigel into six-to eight- week old male nu/nu nude mice.
                    Experimental
                    Result(s)		 The combination of ellagic acid with erlotinib has synergistic effects against EGFR H773_V774 insH mutation.
Target and Pathway
Target(s) Carbonic anhydrase (CA)  Molecule Info  [7]
Casein kinase II alpha (CSNK2A1)  Molecule Info  [8]
Glycogen synthase kinase-3 beta (GSK-3B)  Molecule Info  [9]
Heat shock protein 70 (HSP70)  Molecule Info  [10]
Mothers against decapentaplegic 3 (SMAD3)  Molecule Info  [10]
Squalene monooxygenase (SQLE)  Molecule Info  [11]
Tyrosine-protein kinase SYK (SYK)  Molecule Info  [9]
KEGG Pathway ErbB signaling pathway Click to Show/Hide
2 Chemokine signaling pathway
3 Cell cycle
4 PI3K-Akt signaling pathway
5 Wnt signaling pathway
6 Hedgehog signaling pathway
7 Axon guidance
8 Hippo signaling pathway
9 Focal adhesion
10 Signaling pathways regulating pluripotency of stem cells
11 T cell receptor signaling pathway
12 B cell receptor signaling pathway
13 Neurotrophin signaling pathway
14 Dopaminergic synapse
15 Insulin signaling pathway
16 Melanogenesis
17 Prolactin signaling pathway
18 Thyroid hormone signaling pathway
19 Non-alcoholic fatty liver disease (NAFLD)
20 Alzheimer's disease
21 Hepatitis C
22 Measles
23 Influenza A
24 HTLV-I infection
25 Epstein-Barr virus infection
26 Pathways in cancer
27 Colorectal cancer
28 Endometrial cancer
29 Prostate cancer
30 Basal cell carcinoma
31 Ribosome biogenesis in eukaryotes
32 NF-kappa B signaling pathway
33 Adherens junction
34 Tight junction
35 Herpes simplex infection
36 Steroid biosynthesis
37 Sesquiterpenoid and triterpenoid biosynthesis
38 Metabolic pathways
39 Biosynthesis of secondary metabolites
40 Biosynthesis of antibiotics
41 Osteoclast differentiation
42 Platelet activation
43 Natural killer cell mediated cytotoxicity
44 Fc epsilon RI signaling pathway
45 Fc gamma R-mediated phagocytosis
46 Tuberculosis
47 Viral carcinogenesis
NetPath Pathway FSH Signaling Pathway Click to Show/Hide
Panther Pathway Alzheimer disease-presenilin pathway Click to Show/Hide
2 Angiogenesis
3 Cadherin signaling pathway
4 Hedgehog signaling pathway
5 Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway
6 Insulin/IGF pathway-protein kinase B signaling cascade
7 Interleukin signaling pathway
8 PDGF signaling pathway
9 PI3 kinase pathway
10 Wnt signaling pathway
11 Ras Pathway
12 CCKR signaling map ST
13 B cell activation
Pathwhiz Pathway Steroid Biosynthesis Click to Show/Hide
2 Fc Epsilon Receptor I Signaling in Mast Cells
Pathway Interaction Database LPA receptor mediated events Click to Show/Hide
2 Degradation of beta catenin
3 Reelin signaling pathway
4 Presenilin action in Notch and Wnt signaling
5 Integrin-linked kinase signaling
6 CDC42 signaling events
7 LKB1 signaling events
8 Canonical Wnt signaling pathway
9 Role of Calcineurin-dependent NFAT signaling in lymphocytes
10 Glucocorticoid receptor regulatory network
11 C-MYC pathway
12 Regulation of Androgen receptor activity
13 BMP receptor signaling
14 Hedgehog signaling events mediated by Gli proteins
15 Signaling events mediated by Stem cell factor receptor (c-Kit)
16 Validated transcriptional targets of deltaNp63 isoforms
17 Aurora A signaling
18 Insulin-mediated glucose transport
19 Class I PI3K signaling events mediated by Akt
20 p53 pathway
21 Trk receptor signaling mediated by PI3K and PLC-gamma
22 BCR signaling pathway
23 Atypical NF-kappaB pathway
24 DNA-PK pathway in nonhomologous end joining
25 E-cadherin signaling in the nascent adherens junction
26 Lissencephaly gene (LIS1) in neuronal migration and development
27 PDGFR-alpha signaling pathway
28 Signaling mediated by p38-alpha and p38-beta
29 Alpha-synuclein signaling
30 Fc-epsilon receptor I signaling in mast cells
31 GMCSF-mediated signaling events
32 Osteopontin-mediated events
33 FAS (CD95) signaling pathway
34 Thromboxane A2 receptor signaling
35 IL2-mediated signaling events
36 Class I PI3K signaling events
Reactome Degradation of beta-catenin by the destruction complex Click to Show/Hide
2 AKT phosphorylates targets in the cytosol
3 Regulation of HSF1-mediated heat shock response
4 CRMPs in Sema3A signaling
5 Disassembly of the destruction complex and recruitment of AXIN to the membrane
6 S33 mutants of beta-catenin aren't phosphorylated
7 S37 mutants of beta-catenin aren't phosphorylated
8 S45 mutants of beta-catenin aren't phosphorylated
9 T41 mutants of beta-catenin aren't phosphorylated
10 Degradation of GLI2 by the proteasome
11 Constitutive Signaling by AKT1 E17K in Cancer
12 Condensation of Prometaphase Chromosomes
13 Cholesterol biosynthesis
14 Activation of gene expression by SREBF (SREBP)
15 GPVI-mediated activation cascade
16 FCGR activation
17 Regulation of actin dynamics for phagocytic cup formation
18 Role of phospholipids in phagocytosis
19 DAP12 signaling
20 Fc epsilon receptor (FCERI) signaling
21 Role of LAT2/NTAL/LAB on calcium mobilization
22 FCERI mediated MAPK activation
23 FCERI mediated Ca+2 mobilization
24 Integrin alphaIIb beta3 signaling
25 Interleukin-2 signaling
26 CLEC7A (Dectin-1) signaling
27 Dectin-2 family
28 Regulation of signaling by CBL
29 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
WikiPathways DNA Damage Response (only ATM dependent) Click to Show/Hide
2 Senescence and Autophagy in Cancer
3 Notch Signaling Pathway
4 Glycogen Metabolism
5 Insulin Signaling
6 Wnt Signaling Pathway
7 Wnt Signaling Pathway and Pluripotency
8 IL-6 signaling pathway
9 Wnt Signaling Pathway Netpath
10 Copper homeostasis
11 Focal Adhesion
12 Hair Follicle Development: Induction (Part 1 of 3)
13 Cardiac Hypertrophic Response
14 Degradation of beta-catenin by the destruction complex
15 T-Cell Receptor and Co-stimulatory Signaling
16 Cardiac Progenitor Differentiation
17 BDNF signaling pathway
18 Corticotropin-releasing hormone
19 B Cell Receptor Signaling Pathway
20 IL17 signaling pathway
21 Neural Crest Differentiation
22 Alzheimers Disease
23 IL-7 Signaling Pathway
24 Regulation of Microtubule Cytoskeleton
25 TWEAK Signaling Pathway
26 Leptin signaling pathway
27 Semaphorin interactions
28 Cell Cycle
29 MicroRNAs in cardiomyocyte hypertrophy
30 Androgen receptor signaling pathway
31 IL-5 Signaling Pathway
32 Mitotic Prometaphase
33 TNF alpha Signaling Pathway
34 L1CAM interactions
35 IL-2 Signaling Pathway
36 IL-3 Signaling Pathway
37 Fc epsilon receptor (FCERI) signaling
38 Signaling by the B Cell Receptor (BCR)
39 Interleukin-2 signaling
40 Fcgamma receptor (FCGR) dependent phagocytosis
41 DAP12 interactions
42 RANKL/RANK Signaling Pathway
43 Integrin alphaIIb beta3 signaling
44 GPVI-mediated activation cascade
45 Regulation of toll-like receptor signaling pathway
References
Reference 1 Ellagic acid attenuates testicular disruption in rheumatoid arthritis via targeting inflammatory signals, oxidative perturbations and apoptosis. Life Sci. 2019 Dec 15;239:117012.
Reference 2 Combining Ellagic Acid with Temozolomide Mediates the Cadherin Switch and Angiogenesis in a Glioblastoma Model. World Neurosurg. 2019 Dec;132:e178-e184.
Reference 3 Ellagic Acid Enhances the Antitumor Efficacy of Bevacizumab in an In Vitro Glioblastoma Model. World Neurosurg. 2019 Dec;132:e59-e65.
Reference 4 Synergistic Effects of Ellagic Acid and Sorafenib on Hepatocytes and Mitochondria Isolated from a Hepatocellular Carcinoma Rat Model. Nutr Cancer. 2020 Oct 8;1-9.
Reference 5 Effects of ellagic acid on chemosensitivity to 5-fluorouracil in colorectal carcinoma cells. Anticancer Res. 2012 Oct;32(10):4413-8.
Reference 6 Combination effects of ellagic acid with erlotinib in a Ba/F3 cell line expressing EGFR H773_V774 insH mutation. Thorac Cancer. 2020 Aug;11(8):2101-2111.
Reference 7 Carbonic anhydrase inhibitors. Inhibition of mammalian isoforms I-XIV with a series of natural product polyphenols and phenolic acids. Bioorg Med Chem. 2010 Mar 15;18(6):2159-2164.
Reference 8 Structural insight into human CK2alpha in complex with the potent inhibitor ellagic acid. Bioorg Med Chem Lett. 2009 Jun 1;19(11):2920-3.
Reference 9 Identification of ellagic acid as potent inhibitor of protein kinase CK2: a successful example of a virtual screening application. J Med Chem. 2006 Apr 20;49(8):2363-6.
Reference 10 In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6.
Reference 11 Ellagitannins and hexahydroxydiphenoyl esters as inhibitors of vertebrate squalene epoxidase. J Nat Prod. 2001 Aug;64(8):1010-4.
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