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↝, beneficial effects of caffeic acid and ellagic acid were dependent upon the gut microbiota.
eff↑, caffeic acid, ferulic acid, and ellagic acid were also able to significantly ameliorate the severity of colitis, including reduced weight loss, decreased DAI score, relief of colon shortening and lower infiltration of inflammatory cell in the colonic
Weight↑,

1616- CUR,  EA,    Kinetics of Inhibition of Monoamine Oxidase Using Curcumin and Ellagic Acid
- in-vitro, Nor, NA
*MAOA↓, MAO activity was inhibited by curcumin and ellagic acid
*Dose∅, however, higher half maximal inhibitory concentrations of curcumin (500.46 nM) and ellagic acid (412.24 nM)
Dose?, MAO-B by curcumin (IC50 500.46 nM) and ellagic acid (IC50 412.24 nM)

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↑, combination of Curcumin and Ellagic acid at various concentrations showed better anticancer properties than either of the drug when used alone as evidenced by MTT assay
Dose∅, IC50 value for Curcumin is calculated as 16.52 mM and for Ellagic acid the IC50 Value is 19.47 mM. The combination of Curcumin and Ellagic acid has IC50 value 10.9 mM.
ROS↑, Curcumin alone increases the ROS level significantly. Similarly the C + E treated cells exhibited a very high magnitude of ROS level.
DNAdam↑, Curcumin and Ellagic acid show mild degree of DNA damage at this concentration but the C + E treated cells shows greater degree of DNA damage
P53↑, C + E treated cells show greater degree of stabilization of p53
P21↑, Elevated expression of p21 in response to Curcumin and C + E treatment
BAX↑, But the C + E treated cells showed higher expression of Bax
Dose∅, Curcumin daily shows detectable levels of Curcumin in plasma and urine and the concentration is close to 11.1 nMol/l

1618- EA,    A comprehensive review on Ellagic acid in breast cancer treatment: From cellular effects to molecular mechanisms of action
- Review, BC, NA
TumCCA↑, suppresses the growth of BC cells by arresting the cell cycle in the G0/G1 phase,
TumCMig↓, suppresses migration, invasion, and metastatic
TumCI↓,
TumMeta↓,
Apoptosis↑, stimulates apoptosis in MCF-7 cells via TGF-β/Smad3 signaling axis
TGF-β↓,
SMAD3↓,
CDK6↓, inhibits CDK6 that is important in cell cycle regulation,
PI3K↓, inhibits the PI3K/AKT pathway
Akt↓,
angioG↓,
VEGFR2↓, reduces VEGFR-2 tyrosine kinase activity
MAPK↓,
NEDD9↓, downregulated protein 9 (NEDD-9)
NF-kB↓, EA suppressed NF-κB precursor protein p105
eff↑, They showed that the encapsulation of EA in biodegradable polymeric nanoparticles would improve the bioavailability after oral administration and also enhance the anticancer properties
eff↑, Chitosan nanoparticles and EA with high anticancer efficacy could be a suitable therapeutic strategy
RadioS↑, showed that the synergistic effect of EA combined with radiotherapy/chemotherapy resulted in increased DNA damage and apoptosis as well as decreased levels of MGMT expression
ChemoSen↑,
DNAdam↑,
eff↑, combination of Paclitaxel and EA has shown promise in inhibiting tumor growth and metastasis in experimental BC models.
*toxicity∅, 630 mg/kg is the LD50 of EA in the rat population.
*toxicity∅, no-observed adverse effect level of EA is 2000 mg/kg body weight

4832- EA,    Experimental Evidence of the Antitumor, Antimetastatic and Antiangiogenic Activity of Ellagic Acid
*antiOx↑, Ellagic acid (EA) is a naturally occurring polyphenolic compound endowed with strong antioxidant and anticancer properties that is present in high quantity in a variety of berries, pomegranates, and dried fruits.
*AntiCan↑,
TumCMig↓, Moreover, EA can inhibit tumour cell migration, extra-cellular matrix invasion and angiogenesis,
angioG↓,
ChemoSen↑, EA may increase tumour sensitivity to chemotherapy and radiotherapy.
RadioS↑,
*chemoP↑, EA oral administration as supportive therapy to standard chemotherapy has been recently evaluated in small clinical studies with colorectal or prostate cancer patients.
*BioAv↓, Overall, EA shows a low bioavailability (0.1–0.4 mmol/L, equivalent to 30–120 ng/mL, with respect to 0.5–18.6 mmol/L, equivalent to 0.1–4 mg/mL for Uro)
eff↓, that hampers its beneficial effects to human health after in vivo oral administration.
selectivity↑, induced apoptosis in colon cancer Caco-2 cells but did not show any toxic effect in normal human lung fibroblasts.
MMP2↓, decreased levels of pro-matrix metalloproteinase-2 (pro-MMP-2 or gelatinase), pro-MMP-9 (or gelatinase B) and vascular endothelial growth factor
MMP9↓,
VEGF↓,
TumCCA↑, Similar results were obtained with HCT-15 and HCT-116 cell lines, where EA exposure promoted cell cycle arrest, induced apoptosis and increased the production of reactive oxygen intermediates
Apoptosis↑,
ROS↑,
BioAv↑, To overcome EA poor water solubility and oral bio-availability EA-encapsulated chitosan nanoparticles were produced

4341- EA,    Novel Bioactivity of Ellagic Acid in Inhibiting Human Platelet Activation
- in-vitro, NA, NA
*AntiAg↑, Ellagic acid (20 to 80 μ M) exhibited a potent activity in inhibiting platelet aggregation stimulated by collagen; however, it did not inhibit platelet aggregation stimulated by thrombin, arachidonic acid, or U46619.
*AntiAg↑, Treatment with ellagic acid (50 and 80 μ M) significantly inhibited platelet activation stimulated by collagen; this alteration was accompanied by the inhibition of relative [Ca(2+)] i mobilization, and the phosphorylation of phospholipase C (PLC) γ

4255- EA,    Effects of nutritional interventions on BDNF concentrations in humans: a systematic review
- Review, NA, NA
*BDNF↑, Supplementation with ellagic acid significantly increased plasma BDNF concentrations in overweight subjects but not in healthy subjects

4254- EA,    Chronic administration of ellagic acid improved the cognition in middle-aged overweight men
- Human, Obesity, NA
*LDL↓, ellagic acid treatment improved the levels of blood lipid metabolism with a 4.7% decline in total cholesterol, 7.3% decline in triglycerides, 26.5% increase in high-density lipoprotein, and 6.5% decline in low-density lipoprotein.
*HDL↑,
*BDNF↑, ellagic acid increased plasma BDNF by 21.2% in the overweight group and showed no effects on normal-weight participants
*cognitive↑, ellagic acid has a potential to restore cognitive performance related to mild age-related declines

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↑, The current study indicates that Ellagic acid intervention has a favorable effect on depression in MS patients.
*BDNF↑, we found a significant elevation in circulating levels of BDNF and serotonin.
*5HT↑,
*antiOx↑, associated to its antioxidative, anti-inflammatory, immunomodulatory, antidiabetic, and anticancer properties (Gupta et al., 2021)
*Inflam↓,
*AntiCan↑,
*QoL↑, Ellagic acid improves bowel function and enhances the quality of life for individuals suffering from irritable bowel syndrome (IBS)
*neuroP↑, Ellagic acid may have neuroprotective effect by regulating the hypothalamic–pituitary–adrenal (HPA) axis and neurotransmitters in animal's brain
*cognitive↑, Ellagic acid supplementation may also improve mood and cognitive function like memory and learning in rats (Gupta et al., 2021).
*memory↑,

4252- EA,    Effect of ellagic acid on BDNF/PI3K/AKT-mediated signaling pathways in mouse models of depression
- in-vivo, NA, NA
*BDNF↑, EA treatment caused an increase in hippocampal BDNF and pAKT1 levels in mice.
*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↓, Ellagic acid (5) inhibited AChE (IC50 = 41.7 µM : All five compounds weakly inhibited BChE and BACE-1.
*BACE↓,
*MAOB↓, inhibited MAO-B by more than 50%.

2402- EA,    Ellagic Acid and Its Metabolites as Potent and Selective Allosteric Inhibitors of Liver Pyruvate Kinase
- in-vitro, NA, NA
PKL↓, see table 1

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↑, potent anti-tumor activity similar to anti-PD-1 antibody.
PD-L1↓, potent anti-tumor effect via PD-1/PD-L1 blockade

1621- EA,    The multifaceted mechanisms of ellagic acid in the treatment of tumors: State-of-the-art
- Review, Var, NA
AntiCan↑, Studies have shown its anti-tumor effect in gastric cancer, liver cancer, pancreatic cancer, breast cancer, colorectal cancer, lung cancer and other malignant tumors
Apoptosis↑,
TumCP↓,
TumMeta↓,
TumCI↓,
TumAuto↑,
VEGFR2↓, inhibition of VEGFR-2 signaling
MAPK↓, MAPK and PI3K/Akt pathways
PI3K↓,
Akt↓,
PD-1↓, Downregulation of VEGFR-2 and PD-1 expression
NOTCH↓, Inhibition of Akt and Notch
PCNA↓, regulation of the expression of proliferation-related proteins PCNA, Ki67, CyclinD1, CDK-2, and CDK-6
Ki-67↓,
cycD1↓,
CDK2↑,
CDK6↓,
Bcl-2↓,
cl‑PARP↑, up-regulated the expression of cleaved PARP, Bax, Active Caspase3, DR4, and DR5
BAX↑,
Casp3↑,
DR4↑,
DR5↑,
Snail↓, down-regulated the expression of Snail, MMP-2, and MMP-9
MMP2↓,
MMP9↓,
TGF-β↑, up-regulation of TGF-β1
PKCδ↓, Inhibition of PKC signaling
β-catenin/ZEB1↓, decreases the expression level of β-catenin
SIRT1↓, down-regulates the expression of anti-apoptotic protein, SIRT1, HuR, and HO-1 protein
HO-1↓,
ROS↑, up-regulates ROS
CHOP↑, activating the CHOP signaling pathway to induce apoptosis
Cyt‑c↑, releases cytochrome c
MMP↓, decreases mitochondrial membrane potential and oxygen consumption,
OCR↓,
AMPK↑, activates AMPK, and downregulates HIF-1α expression
Hif1a↓,
NF-kB↓, inhibition of NF-κB pathway
E-cadherin↑, Upregulates E-cadherin, downregulates vimentin and then blocks EMT progression
Vim↓,
EMT↓,
LC3II↑, Up-regulation of LC3 – II expression and down-regulation of CIP2A
CIP2A↓,
GLUT1↓, regulation of glycolysis-related gene GLUT1 and downstream protein PDH expression
PDH↝,
MAD↓, Downregulation of MAD, LDH, GR, GST, and GSH-Px related protein expressio
LDH↓,
GSTs↑,
NOTCH↓, inhibited the expression of Akt and Notch protein
survivin↓, survivin and XIAP was also significantly down-regulated
XIAP↓,
ER Stress↑, through ER stress
ChemoSideEff↓, could improve cisplatin-induced hepatotoxicity in colorectal cancer cells
ChemoSen↑, Enhancing chemosensitivity

1620- EA,  Rad,    Radiosensitizing effect of ellagic acid on growth of Hepatocellular carcinoma cells: an in vitro study
- in-vitro, Liver, HepG2
ROS↑, Treatment of HepG2 cells with EA and gamma radiation showed increased reactive oxygen species generation
P53↑, up regulation of p53 protein expression
TumCCA↑, combination treatment increased G2/M phase cell population
IL6↓, decreased IL-6, COX–2 and TNF-α expression
COX2↓,
TNF-α↓,
MMP↓, caused a loss in mitochondrial membrane potential
angioG↓, decreased level of angiogenesis marker MMP-9
MMP9↓,
BAX↑,
Casp3↑,
Apoptosis↑,
RadioS↑,
TBARS↑, EA increased TBARS level in HepG2 cells after irradiation
GSH↓, EA decreased the reduced glutathione content in HepG2 cells after irradiation
Bax:Bcl2↑, Combination treatment increased the Bax/Bcl2 ratio
p‑NF-kB↓, EA along with radiation decreased p-NF-κB level in tumour cells
p‑STAT3↓, Radiation and EA combination treatment decreased p-STAT3 level in tumour cells

1619- EA,  CUR,    Antimutagenic Effect of the Ellagic Acid and Curcumin Combinations
- in-vitro, Nor, NA
eff↑, In both strains, the antimutagenic activity of two combinations (3 μg of EA+3 μg of CRC and 30 μg of EA+30 μg of CRC mixed with 1 μg of AFB1) was significantly higher

1605- EA,    Ellagic Acid and Cancer Hallmarks: Insights from Experimental Evidence
- Review, Var, NA
*BioAv↓, Within the gastrointestinal tract, EA has restricted bioavailability, primarily due to its hydrophobic nature and very low water solubility.
antiOx↓, strong antioxidant properties [12,13], anti-inflammatory effects
Inflam↓,
TumCP↓, numerous studies indicate that EA possesses properties that can inhibit cell proliferation
TumCCA↑, achieved this by causing cell cycle arrest at the G1 phase
cycD1↓, reduction of cyclin D1 and E levels, as well as to the upregulation of p53 and p21 proteins
cycE↓,
P53↑,
P21↑,
COX2↓, notable reduction in the protein expression of COX-2 and NF-κB as a result of this treatment
NF-kB↓,
Akt↑, suppressing Akt and Notch signaling pathways
NOTCH↓,
CDK2↓,
CDK6↓,
JAK↓, suppression of the JAK/STAT3 pathway
STAT3↓,
EGFR↓, decreased expression of epidermal growth factor receptor (EGFR)
p‑ERK↓, downregulated the expression of phosphorylated ERK1/2, AKT, and STAT3
p‑Akt↓,
p‑STAT3↓,
TGF-β↓, downregulation of the TGF-β/Smad3
SMAD3↓,
CDK6↓, EA demonstrated the capacity to bind to CDK6 and effectively inhibit its activity
Wnt/(β-catenin)↓, ability of EA to inhibit phosphorylation of EGFR
Myc↓, Myc, cyclin D1, and survivin, exhibited decreased levels
survivin↓,
CDK8↓, diminished CDK8 level
PKCδ↓, EA has demonstrated a notable downregulatory impact on the expression of classical isoenzymes of the PKC family (PKCα, PKCβ, and PKCγ).
tumCV↓, EA decreased cell viability
RadioS↑, further intensified when EA was combined with gamma irradiation.
eff↑, EA additionally potentiated the impact of quercetin in promoting the phosphorylation of p53 at Ser 15 and increasing p21 protein levels in the human leukemia cell line (MOLT-4)
MDM2↓, finding points to the ability of reduced MDM2 levels
XIAP↓, downregulation of X-linked inhibitor of apoptosis protein (XIAP).
p‑RB1↓, EA exerted a decrease in phosphorylation of pRB
PTEN↑, EA enhances the protein phosphatase activity of PTEN in melanoma cells (B16F10)
p‑FAK↓, reduced phosphorylation of focal adhesion kinase (FAK)
Bax:Bcl2↑, EA significantly increases the Bax/Bcl-2 rati
Bcl-xL↓, downregulates Bcl-xL and Mcl-1
Mcl-1↓,
PUMA↑, EA also increases the expression of Bcl-2 inhibitory proapoptotic proteins PUMA and Noxa in prostate cancer cells
NOXA↑,
MMP↓, addition to the reduction in MMP, the release of cytochrome c into the cytosol occurs in pancreatic cancer cells
Cyt‑c↑,
ROS↑, induction of ROS production
Ca+2↝, changes in intracellular calcium concentration, leading to increased levels of EndoG, Smac/DIABLO, AIF, cytochrome c, and APAF1 in the cytosol
Endoglin↑,
Diablo↑,
AIF↑,
iNOS↓, decreased expression of Bcl-2, NF-кB, and iNOS were observed after exposure to EA at concentrations of 15 and 30 µg/mL
Casp9↑, increase in caspase 9 activity in EA-treated pancreatic cancer cells PANC-1
Casp3↑, EA-induced caspase 3 activation and PARP cleavage in a dose-dependent manner (10–100 µmol/L)
cl‑PARP↑,
RadioS↑, EA sensitizes and reduces the resistance of breast cancer MCF-7 cells to apoptosis induced by γ-radiation
Hif1a↓, EA reduced the expression of HIF-1α
HO-1↓, EA significantly reduced the levels of two isoforms of this enzyme, HO-1, and HO-2, and increased the levels of sEH (Soluble epoxide hydrolase) in LnCap
HO-2↓,
SIRT1↓, EA-induced apoptosis was associated with reduced expression of HuR and Sirt1
selectivity↑, A significant advantage of EA as a potential chemopreventive, anti-tumor, or adjuvant therapeutic agent in cancer treatment is its relative selectivity
Dose∅, EA significantly 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
NHE1↓, EA had the capacity to regulate cytosolic pH by downregulating the expression of the Na+/H+ exchanger (NHE1)
Glycolysis↓, led to intracellular acidification with subsequent impairment of glycolysis
GlucoseCon↓, associated with a decrease in the cellular uptake of glucose
lactateProd↓, notable reduction in lactate levels in supernatant
PDK1?, inhibit pyruvate dehydrogenase kinase (PDK) -bind and inhibit PDK3
PDK1?,
ECAR↝, EA has been shown to influence extracellular acidosis
COX1↓, downregulation of cancer-related genes, including COX1, COX2, snail, twist1, and c-Myc.
Snail↓,
Twist↓,
cMyc↓,
Telomerase↓, EA, might dose-dependently inhibit telomerase activity
angioG↓, EA may inhibit angiogenesis
MMP2↓, EA demonstrated a notable reduction in the secretion of matrix metalloproteinase (MMP)-2 and MMP-9.
MMP9↓,
VEGF↓, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
Dose↝, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
PD-L1↓, EA downregulated the expression of the immune checkpoint PD-L1 in tumor cells
eff↑, EA might potentially enhance the efficacy of anti-PD-L1 treatment
SIRT6↑, EA exhibited statistically significant upregulation of sirtuin 6 at the protein level in Caco2 cells
DNAdam↓, increase in DNA damage

1617- EA,  CUR,    The inhibition of human glutathione S-transferases activity by plant polyphenolic compounds ellagic acid and curcumin
- in-vitro, Nor, NA
Dose∅, ellagic acid and curcumin were shown to inhibit GSTs A1-1, A2-2, M1-1, M2-2 and P1-1with IC50 values ranging from 0.04 to 5 μM
GSTs↓,

27- EA,    Ellagic acid inhibits human pancreatic cancer growth in Balb c nude mice
- in-vivo, PC, NA
HH↓,
Gli1↓,
GLI2↓,
cycD1↓,
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∅, 800 mg of extract. Results indicate that ellagic acid (EA) from the extract is bioavailable, with an observed C(max) of 33 ng/mL at t(max) of 1 h.
*ROS∅, whereas the generation of reactive oxygen species (ROS) was not affected

1614- EA,    Bioavailability of ellagic acid in human plasma after consumption of ellagitannins from pomegranate (Punica granatum L.) juice
- Human, Nor, NA
*BioEnh↝, pomegranate juice (PJ) (180 ml) containing EA (25 mg) and ETs (318 mg, as punicalagins) : EA was detected in human plasma at a maximum concentration (31.9 ng/ml)
*Half-Life∅, maximum concentration (31.9 ng/ml) after 1 h post-ingestion but was rapidly eliminated by 4 h.

1613- EA,    Ellagitannins in Cancer Chemoprevention and Therapy
- Review, Var, NA
ROS↑, pomegranate ET inhibit pro-inflammatory pathways including, but not limited to, the NF-κB pathway, whose activation leads to immune reactions, inflammation, and the transcription of genes involved in cell survival, such as Bclx and inhibitors of apop
angioG↓, ET to inhibit angiogenesis
ChemoSen↑, ET could also be utilized to increase the sensitivity of tumor cells to standard chemotherapeutic drugs
BAX↑, induction of pro-apoptotic mediators (Bax and Bak), downregulation of Bcl-2 and Bcl-XL, and reduced expression of cyclin-dependent kinases 2, 4, 6, and cyclins D1, D2, and E
Bak↑,
Bcl-2↓,
Bcl-xL↓,
CDK2↓,
CDK4↓,
CDK6↓,
cycD1↓,
cycE1↓,
TumCG↓, reduced LNCaP prostate cancer xenograft size, tumor vessel density, VEGF peptide levels and HIF-α expression after four weeks of treatment in severe combined immunodeficient mice
VEGF↓,
Hif1a↓,
eff↑, Oenothein B, a macrocyclic ET, and quercetin-3-O-glucuronide from Epilobium sp. herbs—used in traditional medicine to treat benign prostatic hyperplasia and prostatic adenoma—have been proven to strongly inhibit the proliferation of human prostate ca
COX2↓, pomegranate ET (i.e., punicalagin and ellagic acid) have been shown to suppress cyclooxygenase-2 (COX-2) protein expression in human colon cancer (HT-29) cells
TumCCA↑, pomegranate ET and their metabolites, i.e., urolithins A and C, inhibit HT-29 cells proliferation via G0/G1 and G2/M arrest
selectivity↑, interestingly, normal human breast epithelial cells (MCF-10A) were far less sensitive to the inhibitory effect of polyphenol-rich fractions.
Wnt/(β-catenin)↓, suppression of Wnt/β-catenin
*toxicity∅, LD50 of a standardized pomegranate fruit extract containing 30% punicalagin in Wistar rats was >5 g/kg b.w.,

1612- EA,    Negative Effect of Ellagic Acid on Cytosolic pH Regulation and Glycolytic Flux in Human Endometrial Cancer Cell
- in-vitro, EC, NA
NHE1↓, 48 hour treatment with Ellagic acid (20 µM) significantly decreased NHE1 transcript levels by 75%, NHE1 protein abundance by 95%
i-pH↓, pHi from 7.24 ± 0.01 to 7.02 ± 0.01
ROS↓, ROS by 82%
GlucoseCon↓, glucose uptake by 58%
NHE1↓, Treatment with EA is followed by a significant decline of NHE1 transcript levels, NHE1 protein abundance, and Na+/H+ exchanger activity.
Glycolysis↓, EA down-regulates expression and function of the Na+/H+ exchanger, decreases cytosolic acidification with subsequent impairment of 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↓, ellagic acid is widely studied due to its antioxidant and parasite-inhibiting properties. However, its low oral bioavailability remains a concern
eff↑, very effective inhibitor of Plasmodium falciparum, showing an in vitro activity ranging from 100 to 300 nM
*BioAv↓, ellagic acid remains its very low oral bioavailability (<30% in mice), which impedes its use as an oral antimalarial drug and was partially linked to its low hydrosolubility.
ROS↑, when in contact with the parasite environment, could become pro-oxidant and efficient

1610- EA,    Anticancer Effect of Pomegranate Peel Polyphenols against Cervical Cancer
- Review, Cerv, NA
TumCCA↑, EA had a dose-dependent apoptotic effect on HeLa cells caused by cell cycle arrest in the G1 phase via the regulation of STAT3
STAT3↓,
P21↑, increase in the expression of both p21 mRNA and protein
IGFBP7↑, increase in igfb7
Akt↓, inhibition of the Akt/mTOR signaling
mTOR↓,
ROS↑, increase in the production of ROS and DNA damage
DNAdam↑,
P53↑, restored activity of p53 and p21 genes and
P21↑,
BAX↑, increased expression of the 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↑, Hull blackberry fruits into five growth periods according to color and determined the EA content in the fruits in each period. The EA content in the green fruit stage was the highest at 5.67 mg/g FW
Dose∅, EA inhibited HeLa cells with an IC50 of 35 μg/mL
*BioAv↑, EA is not sensitive to high temperatures and is not highly soluble in many solvents.
selectivity↑, selectivity index varied from 7.4 for Hela to about 1 for A549
TumCP↓, EA reduced the proliferation of human cervical cancer HeLa, SiHa, and C33A cells in a dose- and time-dependent manner, and the inhibitory effect was significantly more pronounced in HeLa cells than in SiHa and C33A cells
Casp↑, EA reduced the proliferation of human cervical cancer HeLa, SiHa, and C33A cells in a dose- and time-dependent manner, and the inhibitory effect was significantly more pronounced in HeLa cells than in SiHa and C33A cells
PTEN↑,
TSC1↑,
mTOR⇅,
Akt↓, AKT, PDK1 expression were down-regulated
PDK1↓,
E6↓, mRNA levels of E6/E7 were determined to decrease gradually with the increase in EA incubation time and concentration
E7↓,
DNAdam↑, When DNA damage is introduced into cells from exogenous or endogenous sources there is an increase in the amount of intracellular reactive oxygen species (ROS)
ROS↑,
*BioAv↓, EA cannot be exploited for in vivo therapeutic applications in the current situation because of its poor water solubility and accordingly low bioavailability.
*BioEnh↑, As Lei [52] reported that EA in pomegranate leaf is rapidly absorbed and distributed as well as eliminated in rats
*Half-Life∅, blood concentration peaked at 0.5 h with Cmax = 7.29 μg/mL, and the drug concentration decreased to half of the original after 57 min of administration

1607- EA,    Exploring the Potential of Ellagic Acid in Gastrointestinal Cancer Prevention: Recent Advances and Future Directions
- Review, GC, NA
STAT3↓, EA inhibits STAT3 signaling
TumCP↓, EA inhibits cell proliferation, induces apoptosis
Apoptosis↑,
NF-kB↓, inhibiting nuclear factor-kappa B
EMT↓, suppressing epithelial–mesenchymal transition
RadioS↑, In liver cancer, EA exhibits radio-sensitizing effects
antiOx↑, As a potential antioxidant agent,
COX1↓, EA suppresses the expression of several factors, including COX1, COX2, c-myc, snail, and twist1
COX2↓,
cMyc↓,
Snail↓,
Twist↓,
MMP2↓, significantly decreased MMP-2 and MMP-9 expression and activity.
P90RSK↓,
CDK8↓, downregulate CDK8 expression and activity
PI3K↓, inactivating PI3K/Akt signaling
Akt↓,
TumCCA↑, promote cell cycle arrest
Casp8↑, ctivating caspase-8, and lowering proliferating cell nuclear antigen (PCNA) expression,
PCNA↓,
TGF-β↓,
Shh↓, suppression of the Akt, Shh, and Notch pathways, EA can prevent the growth, angiogenesis, and metastasis of pancreatic cancer
NOTCH↓,
IL6↓,
ALAT↓, decreasing liver injury biomarkers such as alanine transaminase (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST)
ALP↓,
AST↓,
VEGF↓,
P21↑,
*toxicity∅, no toxicity was found for a 50% effective dose by the intraperitoneal route inferior to 1 mg/kg/day
*Inflam↓, ncluding anti-inflammatory [10], anti-oxidant [11], anti-allergic [12], and anti-mutagenic [13] properties, as well as potential health advantages like gastroprotective [14], cardioprotective [15], neuroprotective [16, 17], and hepatoprotective [18,
*cardioP↑,
*neuroP↑,
*hepatoP↑,
ROS↑, Exposure to EAs induced apoptosis, accelerated cell cycle arrest, and elevated the generation of reactive oxygen intermediates [59].
*NRF2↓, As a potential antioxidant agent, it scavenges reactive oxygen species (ROS), and by upregulating of Nrf2,
*GSH↑, Moreover, EA increases reduced glutathione (GSH), which is critical for cellular defense against oxidative stress and liver damage,

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↓,
Apoptosis↑,
PI3K↓, strong inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway by EA
Akt↓,
ROS↑, production of reactive oxygen intermediates, which were examined by 2,7-dichlorodihydrofluorescein diacetate (H2DCF-DA), increased with time, after treatment with EA
Casp3↑, EA promoted the expression of Bax, caspase-3, and cytochrome c, and suppression of Bcl-2 activity in HCT-15 cells
Cyt‑c↑,
Bcl-2↓,
TumCCA↑, induces G2/M phase cell cycle arrest in HCT-15 cells
Dose∅, since 60 lM of the drug concentration could cause attentional loss of cells (60 and 45 % were viable in 12 and 24 h treatment, respectively) for crucial experiments, we used this dosage to assess the effect of EA in killing HCT-15 cells
ALP↓, significant decrease in the activity of ALP at 60 lM concentration of EA for the 12 h treatment
LDH↓, decrease in the activity of LDH in cells was proportional to increase in the incubation time with EA.
PCNA↓, EA down-regulated the expressions of PCNA and cyclin D1
P53↑, EA promoted p53 gene expression
Bax:Bcl2↑, increase in the Bcl-2/Bax ratio

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↓, silibinin, curcumin, resveratrol, and ellagic acid as potential inhibitors of PKM2
Dose↝, IC50 values of 0.91 µM, 1.12 µM, 3.07 µM, and 4.20 µM respectively(enzymatic-assay-based screening)
Dose↝, IC50 against MDA-MB231 cells 208uM, 26uM, 306uM, 20um respectively


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

Results for Effect on Cancer/Diseased Cells:
ACLY↓,1,   AIF↑,1,   Akt↓,7,   Akt↑,1,   p‑Akt↓,2,   ALAT↓,1,   ALP↓,2,   AMPK↑,1,   angioG↓,5,   AntiCan↑,1,   antiOx↓,1,   antiOx↑,1,   AntiTum↑,1,   Apoptosis↑,6,   AST↓,1,   Bak↑,1,   BAX↑,6,   Bax:Bcl2↑,3,   Bcl-2↓,3,   Bcl-xL↓,2,   BioAv↑,1,   Ca+2↝,1,   Casp↑,1,   Casp3↑,4,   Casp8↑,1,   Casp9↑,1,   CDK1/2/5/9↓,1,   CDK2↓,2,   CDK2↑,1,   CDK4↓,1,   CDK6↓,5,   CDK8↓,2,   ChemoSen↑,4,   ChemoSideEff↓,1,   CHOP↑,1,   CIP2A↓,1,   cMyc↓,2,   COX1↓,2,   COX2↓,4,   cycD1↓,5,   cycE↓,1,   cycE1↓,1,   Cyt‑c↑,3,   Diablo↑,1,   DNAdam↓,1,   DNAdam↑,4,   Dose?,1,   Dose↝,3,   Dose∅,6,   DR4↑,1,   DR5↑,1,   E-cadherin↑,2,   E6↓,1,   E7↓,1,   ECAR↝,1,   eff↓,1,   eff↑,11,   eff↝,1,   EGFR↓,1,   EMT↓,2,   Endoglin↑,1,   ER Stress↑,1,   p‑ERK↓,1,   p‑FAK↓,1,   Gli1↓,1,   GLI2↓,1,   GlucoseCon↓,2,   GLUT1↓,1,   Glycolysis↓,2,   GSH↓,1,   GSTs↓,1,   GSTs↑,1,   HEY1↓,1,   HH↓,1,   Hif1a↓,3,   HO-1↓,2,   HO-2↓,1,   IGFBP7↑,1,   IL6↓,2,   Inflam↓,1,   iNOS↓,1,   JAK↓,1,   Ki-67↓,1,   lactateProd↓,1,   LC3II↑,1,   LDH↓,2,   MAD↓,1,   MAPK↓,2,   Mcl-1↓,1,   MDM2↓,1,   MMP↓,3,   MMP2↓,5,   MMP9↓,5,   mTOR↓,1,   mTOR⇅,1,   Myc↓,1,   NEDD9↓,1,   NF-kB↓,4,   p‑NF-kB↓,1,   NHE1↓,3,   NOTCH↓,4,   NOTCH1↓,1,   NOTCH3↓,1,   NOXA↑,1,   OCR↓,1,   P21↑,5,   P53↑,5,   P90RSK↓,1,   cl‑PARP↑,2,   PCNA↓,3,   PD-1↓,1,   PD-L1↓,2,   PDH↝,1,   PDK1?,2,   PDK1↓,1,   i-pH↓,1,   PI3K↓,4,   PKCδ↓,2,   PKL↓,1,   PKM2↓,1,   PTEN↑,2,   PUMA↑,1,   RadioS↑,6,   p‑RB1↓,1,   ROS↓,1,   ROS↑,11,   selectivity↑,4,   Shh↓,2,   SIRT1↓,2,   SIRT6↑,1,   SMAD2↓,1,   SMAD3↓,3,   SMAD4↓,1,   Snail↓,4,   STAT3↓,3,   p‑STAT3↓,2,   survivin↓,2,   TBARS↑,1,   Telomerase↓,1,   TGF-β↓,4,   TGF-β↑,1,   TNF-α↓,1,   TSC1↑,1,   TumAuto↑,1,   TumCCA↑,8,   TumCG↓,1,   TumCI↓,2,   TumCMig↓,2,   TumCP↓,5,   tumCV↓,1,   TumMeta↓,2,   Twist↓,2,   VEGF↓,4,   VEGFR2↓,2,   Vim↓,1,   Weight↑,1,   Wnt/(β-catenin)↓,2,   XIAP↓,2,   β-catenin/ZEB1↓,1,  
Total Targets: 159

Results for Effect on Normal Cells:
5HT↑,1,   AChE↓,1,   p‑AKT1↑,1,   AntiAg↑,2,   AntiCan↑,2,   antiOx↑,2,   BACE↓,1,   BDNF↑,4,   BioAv↓,5,   BioAv↑,1,   BioAv∅,1,   BioEnh↑,1,   BioEnh↝,1,   cardioP↑,1,   chemoP↑,1,   cognitive↑,2,   Dose∅,1,   GSH↑,1,   Half-Life∅,2,   HDL↑,1,   hepatoP↑,1,   Inflam↓,2,   LDL↓,1,   MAOA↓,1,   MAOB↓,1,   memory↑,1,   Mood↑,1,   neuroP↑,2,   NRF2↓,1,   QoL↑,1,   ROS∅,1,   toxicity∅,4,  
Total Targets: 32

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

 

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