Database Query Results : Ellagic acid, ,

EA, Ellagic acid: Click to Expand ⟱
Features:
Polyphenol found in fruits, vegetables, nuts and some mushrooms. Strawberries, raspberries, blackberries, cherries and walnuts, green tea and red wine. Pomegranate arils are a well known source.

- Ellagitannins are high molecular weight polyphenols with a complex structure that includes one or more HHDP groups attached to a sugar.
- Ellagic Acid is the simpler, bioactive compound released when the HHDP groups in ellagitannins cyclize during hydrolysis.
- one best source is raspberries. 100g gives ~50mg(reasonable dose)
- Ellagic acid has very poor oral bioavailability
- Peak plasma EA after high oral intake is typically: <50–100 nM, often much lower, this is far below concentrations used in many in-vitro anticancer studies (5–50 µM).
- efficacy depends on gut metabolism (ie ability to produce Urolithin A)
- also look at Urolithin supplements

Pathways:
Apoptosis Regulation: (Bax, Bad) (Bcl-2, Bcl-xL)
Cell Cycle Arrest: G0/G1 or G2/M phases)
NF-κB (inhibit):
MAPK Pathways: (including ERK1/2, JNK, and p38 MAPK)
PI3K/Akt/mTOR: might downregulate this pathway
p53 Pathway: may influence the expression or activation of p53
Oxidative Stress and Nrf2 Pathway:exhibits antioxidant properties,
Summary:
- Anti-oxidant and metal chelating
- with some evidence it can induce ROS in cancer tumor conditions (mitochondrial stress, redox-unstable cells)
- Works well with Curcumin
- Reduced the viability of cancer cells at a concentration of 10 µmol/L, while in healthy cells, this effect was observed only at a concentration of 200 µmol/L
- Pomegranate juice (PJ) (180 ml) containing EA (25 mg) and ETs (318 mg, as punicalagins, the major fruit ellagitannin). Plasma concentration (31.9 ng/ml) after 1 h post-ingestion but was rapidly eliminated by 4 h. (Hence might be difficult to consume enough EA!!!! to match vitro requirements)
- Likely need > 10mg/kg/day -> *180kg = 1800mg (might be possible)
- Increased the expression of p53 and p21 proteins as well as markers of apoptosis (Bax and caspase-3), and decreases Bcl-2, NF-кB, and iNOS
- EA has restricted bioavailability, primarily due to its hydrophobic nature and very low water solubility.
- Industrial processing of pomegranates for juice production increases the concentration of EA in juices, but freezing reduces concentration

Punica granatum L. Pomegranate 700mg/kg (arils), 38700mg/kg(mesocarp)
Rubus idaeus L. Raspberry 2637–3309mg/kg
jaglandaceae Walnut 410mg/kg(freeEA) 8230mg/kg(totalEA)
Scientific Papers found: Click to Expand⟱
289- ALA,  HCA,  EA,    Cancer Metabolism: Fasting Reset, the Keto-Paradox and Drugs for Undoing
- Analysis, NA, NA
ACLY↓,
2399- CA,  EA,    Polyphenol-rich diet mediates interplay between macrophage-neutrophil and gut microbiota to alleviate intestinal inflammation
- Review, Col, NA
eff↝, eff↑, Weight↑,
1616- CUR,  EA,    Kinetics of Inhibition of Monoamine Oxidase Using Curcumin and Ellagic Acid
- in-vitro, Nor, NA
*MAOA↓, *Dose∅, Dose?,
1609- CUR,  EA,    Curcumin and Ellagic acid synergistically induce ROS generation, DNA damage, p53 accumulation and apoptosis in HeLa cervical carcinoma cells
- in-vitro, Cerv, NA
eff↑, Dose∅, ROS↑, DNAdam↑, P53↑, P21↑, BAX↑, Dose∅,
1618- EA,    A comprehensive review on Ellagic acid in breast cancer treatment: From cellular effects to molecular mechanisms of action
- Review, BC, NA
TumCCA↑, TumCMig↓, TumCI↓, TumMeta↓, Apoptosis↑, TGF-β↓, SMAD3↓, CDK6↓, PI3K↓, Akt↓, angioG↓, VEGFR2↓, MAPK↓, NEDD9↓, NF-kB↓, eff↑, eff↑, RadioS↑, ChemoSen↑, DNAdam↑, eff↑, *toxicity∅, *toxicity∅,
4832- EA,    Experimental Evidence of the Antitumor, Antimetastatic and Antiangiogenic Activity of Ellagic Acid
*antiOx↑, *AntiCan↑, TumCMig↓, angioG↓, ChemoSen↑, RadioS↑, *chemoP↑, *BioAv↓, eff↓, selectivity↑, MMP2↓, MMP9↓, VEGF↓, TumCCA↑, Apoptosis↑, ROS↑, BioAv↑,
4341- EA,    Novel Bioactivity of Ellagic Acid in Inhibiting Human Platelet Activation
- in-vitro, NA, NA
*AntiAg↑, *AntiAg↑,
4255- EA,    Effects of nutritional interventions on BDNF concentrations in humans: a systematic review
- Review, NA, NA
*BDNF↑,
4254- EA,    Chronic administration of ellagic acid improved the cognition in middle-aged overweight men
- Human, Obesity, NA
*LDL↓, *HDL↑, *BDNF↑, *cognitive↑,
4253- EA,    The effects of Ellagic acid supplementation on neurotrophic, inflammation, and oxidative stress factors, and indoleamine 2, 3-dioxygenase gene expression in multiple sclerosis patients with mild to moderate depressive symptoms: A randomized, triple-blind, placebo-controlled trial
- Human, MS, NA - NA, IBD, NA
*Mood↑, *BDNF↑, *5HT↑, *antiOx↑, *Inflam↓, *AntiCan↑, *QoL↑, *neuroP↑, *cognitive↑, *memory↑,
4252- EA,    Effect of ellagic acid on BDNF/PI3K/AKT-mediated signaling pathways in mouse models of depression
- in-vivo, NA, NA
*BDNF↑, *p‑AKT1↑,
3756- EA,    Acetylcholinesterase and monoamine oxidase-B inhibitory activities by ellagic acid derivatives isolated from Castanopsis cuspidata var. sieboldii
- Analysis, AD, NA
*AChE↓, *BACE↓, *MAOB↓,
2402- EA,    Ellagic Acid and Its Metabolites as Potent and Selective Allosteric Inhibitors of Liver Pyruvate Kinase
- in-vitro, NA, NA
PKL↓,
1037- EA,    Unripe Black Raspberry (Rubus coreanus Miquel) Extract and Its Constitute, Ellagic Acid Induces T Cell Activation and Antitumor Immunity by Blocking PD-1/PD-L1 Interaction
- in-vivo, CRC, NA
AntiTum↑, PD-L1↓,
1621- EA,    The multifaceted mechanisms of ellagic acid in the treatment of tumors: State-of-the-art
- Review, Var, NA
AntiCan↑, Apoptosis↑, TumCP↓, TumMeta↓, TumCI↓, TumAuto↑, VEGFR2↓, MAPK↓, PI3K↓, Akt↓, PD-1↓, NOTCH↓, PCNA↓, Ki-67↓, cycD1/CCND1↓, CDK2↑, CDK6↓, Bcl-2↓, cl‑PARP↑, BAX↑, Casp3↑, DR4↑, DR5↑, Snail↓, MMP2↓, MMP9↓, TGF-β↑, PKCδ↓, β-catenin/ZEB1↓, SIRT1↓, HO-1↓, ROS↑, CHOP↑, Cyt‑c↑, MMP↓, OCR↓, AMPK↑, Hif1a↓, NF-kB↓, E-cadherin↑, Vim↓, EMT↓, LC3II↑, CIP2A↓, GLUT1↓, PDH↝, MAD↓, LDH↓, GSTs↑, NOTCH↓, survivin↓, XIAP↓, ER Stress↑, ChemoSideEff↓, ChemoSen↑,
1620- EA,  Rad,    Radiosensitizing effect of ellagic acid on growth of Hepatocellular carcinoma cells: an in vitro study
- in-vitro, Liver, HepG2
ROS↑, P53↑, TumCCA↑, IL6↓, COX2↓, TNF-α↓, MMP↓, angioG↓, MMP9↓, BAX↑, Casp3↑, Apoptosis↑, RadioS↑, TBARS↑, GSH↓, Bax:Bcl2↑, p‑NF-kB↓, p‑STAT3↓,
1619- EA,  CUR,    Antimutagenic Effect of the Ellagic Acid and Curcumin Combinations
- in-vitro, Nor, NA
eff↑,
1605- EA,    Ellagic Acid and Cancer Hallmarks: Insights from Experimental Evidence
- Review, Var, NA
*BioAv↓, antiOx↓, Inflam↓, TumCP↓, TumCCA↑, cycD1/CCND1↓, cycE/CCNE↓, P53↑, P21↑, COX2↓, NF-kB↓, Akt↑, NOTCH↓, CDK2↓, CDK6↓, JAK↓, STAT3↓, EGFR↓, p‑ERK↓, p‑Akt↓, p‑STAT3↓, TGF-β↓, SMAD3↓, CDK6↓, Wnt/(β-catenin)↓, Myc↓, survivin↓, CDK8↓, PKCδ↓, tumCV↓, RadioS↑, eff↑, MDM2↓, XIAP↓, p‑RB1↓, PTEN↑, p‑FAK↓, Bax:Bcl2↑, Bcl-xL↓, Mcl-1↓, PUMA↑, NOXA↑, MMP↓, Cyt‑c↑, ROS↑, Ca+2↝, Endoglin↑, Diablo↑, AIF↑, iNOS↓, Casp9↑, Casp3↑, cl‑PARP↑, RadioS↑, Hif1a↓, HO-1↓, HO-2↓, SIRT1↓, selectivity↑, Dose∅, NHE1↓, Glycolysis↓, GlucoseCon↓, lactateProd↓, PDK1?, PDK1?, ECAR↝, COX1↓, Snail↓, Twist↓, cMyc↓, Telomerase↓, angioG↓, MMP2↓, MMP9↓, VEGF↓, Dose↝, PD-L1↓, eff↑, SIRT6↑, DNAdam↓,
1617- EA,  CUR,    The inhibition of human glutathione S-transferases activity by plant polyphenolic compounds ellagic acid and curcumin
- in-vitro, Nor, NA
Dose∅, GSTs↓,
27- EA,    Ellagic acid inhibits human pancreatic cancer growth in Balb c nude mice
- in-vivo, PC, NA
HH↓, Gli1↓, GLI2↓, cycD1/CCND1↓, CDK1/2/5/9↓, p‑Akt↓, NOTCH1↓, Akt↓, Shh↓, Snail↓, MMP2↓, MMP9↓, BAX↑, E-cadherin↑, NOTCH3↓, HEY1↓,
1615- EA,    Absorption, metabolism, and antioxidant effects of pomegranate (Punica granatum l.) polyphenols after ingestion of a standardized extract in healthy human volunteers
- Human, Nor, NA
*BioAv∅, *ROS∅,
1614- EA,    Bioavailability of ellagic acid in human plasma after consumption of ellagitannins from pomegranate (Punica granatum L.) juice
- Human, Nor, NA
*BioEnh↝, *Half-Life∅,
1613- EA,    Ellagitannins in Cancer Chemoprevention and Therapy
- Review, Var, NA
ROS↑, angioG↓, ChemoSen↑, BAX↑, Bak↑, Bcl-2↓, Bcl-xL↓, CDK2↓, CDK4↓, CDK6↓, cycD1/CCND1↓, cycE1↓, TumCG↓, VEGF↓, Hif1a↓, eff↑, COX2↓, TumCCA↑, selectivity↑, Wnt/(β-catenin)↓, *toxicity∅,
1612- EA,    Negative Effect of Ellagic Acid on Cytosolic pH Regulation and Glycolytic Flux in Human Endometrial Cancer Cell
- in-vitro, EC, NA
NHE1↓, i-pH↓, ROS↓, GlucoseCon↓, NHE1↓, Glycolysis↓,
1611- EA,    Targeting Myeloperoxidase Activity and Neutrophil ROS Production to Modulate Redox Process: Effect of Ellagic Acid and Analogues
- in-vitro, Mal, NA
*BioAv↓, eff↑, *BioAv↓, ROS↑,
1610- EA,    Anticancer Effect of Pomegranate Peel Polyphenols against Cervical Cancer
- Review, Cerv, NA
TumCCA↑, STAT3↓, P21↑, IGFBP7↑, Akt↓, mTOR↓, ROS↑, DNAdam↑, P53↑, P21↑, BAX↑,
1110- EA,  GEM,    Ellagic Acid Resensitizes Gemcitabine-Resistant Bladder Cancer Cells by Inhibiting Epithelial-Mesenchymal Transition and Gemcitabine Transporters
- vitro+vivo, Bladder, NA
TGF-β↓, SMAD2↓, SMAD3↓, SMAD4↓,
1608- EA,    Ellagic Acid from Hull Blackberries: Extraction, Purification, and Potential Anticancer Activity
- in-vitro, Cerv, HeLa - in-vitro, Liver, HepG2 - in-vitro, BC, MCF-7 - in-vitro, Lung, A549 - in-vitro, Nor, HUVECs
eff↑, Dose∅, *BioAv↑, selectivity↑, TumCP↓, Casp↑, PTEN↑, TSC1↑, mTOR⇅, Akt↓, PDK1↓, E6↓, E7↓, DNAdam↑, ROS↑, *BioAv↓, *BioEnh↑, *Half-Life∅,
1607- EA,    Exploring the Potential of Ellagic Acid in Gastrointestinal Cancer Prevention: Recent Advances and Future Directions
- Review, GC, NA
STAT3↓, TumCP↓, Apoptosis↑, NF-kB↓, EMT↓, RadioS↑, antiOx↑, COX1↓, COX2↓, cMyc↓, Snail↓, Twist↓, MMP2↓, P90RSK↓, CDK8↓, PI3K↓, Akt↓, TumCCA↑, Casp8↑, PCNA↓, TGF-β↓, Shh↓, NOTCH↓, IL6↓, ALAT↓, ALP↓, AST↓, VEGF↓, P21↑, *toxicity∅, *Inflam↓, *cardioP↑, *neuroP↑, *hepatoP↑, ROS↑, *NRF2↓, *GSH↑,
1606- EA,    Ellagic acid inhibits proliferation and induced apoptosis via the Akt signaling pathway in HCT-15 colon adenocarcinoma cells
- in-vitro, Colon, HCT15
TumCP↓, cycD1/CCND1↓, Apoptosis↑, PI3K↓, Akt↓, ROS↑, Casp3↑, Cyt‑c↑, Bcl-2↓, TumCCA↑, Dose∅, ALP↓, LDH↓, PCNA↓, P53↑, Bax:Bcl2↑,
2306- SIL,  CUR,  RES,  EA,    Identification of Natural Compounds as Inhibitors of Pyruvate Kinase M2 for Cancer Treatment
- in-vitro, BC, MDA-MB-231
PKM2↓, Dose↝, Dose↝,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 31

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   antiOx↑, 1,   GSH↓, 1,   GSTs↓, 1,   GSTs↑, 1,   HO-1↓, 2,   HO-2↓, 1,   MAD↓, 1,   ROS↓, 1,   ROS↑, 11,   TBARS↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   MMP↓, 3,   OCR↓, 1,   XIAP↓, 2,  

Core Metabolism/Glycolysis ⓘ

ACLY↓, 1,   ALAT↓, 1,   AMPK↑, 1,   cMyc↓, 2,   ECAR↝, 1,   GlucoseCon↓, 2,   Glycolysis↓, 2,   lactateProd↓, 1,   LDH↓, 2,   PDH↝, 1,   PDK1?, 2,   PDK1↓, 1,   PKL↓, 1,   PKM2↓, 1,   SIRT1↓, 2,  

Cell Death ⓘ

Akt↓, 7,   Akt↑, 1,   p‑Akt↓, 2,   Apoptosis↑, 6,   Bak↑, 1,   BAX↑, 6,   Bax:Bcl2↑, 3,   Bcl-2↓, 3,   Bcl-xL↓, 2,   Casp↑, 1,   Casp3↑, 4,   Casp8↑, 1,   Casp9↑, 1,   Cyt‑c↑, 3,   Diablo↑, 1,   DR4↑, 1,   DR5↑, 1,   HEY1↓, 1,   iNOS↓, 1,   MAPK↓, 2,   Mcl-1↓, 1,   MDM2↓, 1,   Myc↓, 1,   NOXA↑, 1,   PUMA↑, 1,   survivin↓, 2,   Telomerase↓, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↑, 1,  

Autophagy & Lysosomes ⓘ

LC3II↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↓, 1,   DNAdam↑, 4,   P53↑, 5,   cl‑PARP↑, 2,   PCNA↓, 3,   SIRT6↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1/2/5/9↓, 1,   CDK2↓, 2,   CDK2↑, 1,   CDK4↓, 1,   cycD1/CCND1↓, 5,   cycE/CCNE↓, 1,   cycE1↓, 1,   P21↑, 5,   p‑RB1↓, 1,   TumCCA↑, 8,  

Proliferation, Differentiation & Cell State ⓘ

CDK8↓, 2,   CIP2A↓, 1,   EMT↓, 2,   p‑ERK↓, 1,   Gli1↓, 1,   HH↓, 1,   IGFBP7↑, 1,   mTOR↓, 1,   mTOR⇅, 1,   NOTCH↓, 4,   NOTCH1↓, 1,   NOTCH3↓, 1,   P90RSK↓, 1,   PI3K↓, 4,   PTEN↑, 2,   Shh↓, 2,   STAT3↓, 3,   p‑STAT3↓, 2,   TumCG↓, 1,   Wnt/(β-catenin)↓, 2,  

Migration ⓘ

Ca+2↝, 1,   E-cadherin↑, 2,   p‑FAK↓, 1,   GLI2↓, 1,   Ki-67↓, 1,   MMP2↓, 5,   MMP9↓, 5,   NEDD9↓, 1,   PKCδ↓, 2,   SMAD2↓, 1,   SMAD3↓, 3,   SMAD4↓, 1,   Snail↓, 4,   TGF-β↓, 4,   TGF-β↑, 1,   TSC1↑, 1,   TumCI↓, 2,   TumCMig↓, 2,   TumCP↓, 5,   TumMeta↓, 2,   Twist↓, 2,   Vim↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 5,   EGFR↓, 1,   Endoglin↑, 1,   Hif1a↓, 3,   VEGF↓, 4,   VEGFR2↓, 2,  

Barriers & Transport ⓘ

GLUT1↓, 1,   NHE1↓, 3,  

Immune & Inflammatory Signaling ⓘ

COX1↓, 2,   COX2↓, 4,   IL6↓, 2,   Inflam↓, 1,   JAK↓, 1,   NF-kB↓, 4,   p‑NF-kB↓, 1,   PD-1↓, 1,   PD-L1↓, 2,   TNF-α↓, 1,  

Cellular Microenvironment ⓘ

i-pH↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 5,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   ChemoSen↑, 4,   Dose?, 1,   Dose↝, 3,   Dose∅, 6,   eff↓, 1,   eff↑, 11,   eff↝, 1,   RadioS↑, 6,   selectivity↑, 4,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   ALP↓, 2,   AST↓, 1,   E6↓, 1,   E7↓, 1,   EGFR↓, 1,   IL6↓, 2,   Ki-67↓, 1,   LDH↓, 2,   Myc↓, 1,   PD-L1↓, 2,  

Functional Outcomes ⓘ

AntiCan↑, 1,   AntiTum↑, 1,   ChemoSideEff↓, 1,   Weight↑, 1,  
Total Targets: 166

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   GSH↑, 1,   HDL↑, 1,   NRF2↓, 1,   ROS∅, 1,  

Core Metabolism/Glycolysis ⓘ

p‑AKT1↑, 1,   LDL↓, 1,  

Migration ⓘ

AntiAg↑, 2,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 2,  

Synaptic & Neurotransmission ⓘ

5HT↑, 1,   AChE↓, 1,   BDNF↑, 4,   MAOA↓, 1,  

Protein Aggregation ⓘ

BACE↓, 1,   MAOB↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 5,   BioAv↑, 1,   BioAv∅, 1,   BioEnh↑, 1,   BioEnh↝, 1,   Dose∅, 1,   Half-Life∅, 2,  

Functional Outcomes ⓘ

AntiCan↑, 2,   cardioP↑, 1,   chemoP↑, 1,   cognitive↑, 2,   hepatoP↑, 1,   memory↑, 1,   Mood↑, 1,   neuroP↑, 2,   QoL↑, 1,   toxicity∅, 4,  
Total Targets: 32

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:74  Target#:%  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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