CK2 ( IC50 = 40 nM )
- Ellagic acid targets protein kinase CK2 (CK2); Ki value for CK2 inhibition was 0.8 μM (competitive inhibition against ATP, detected via radiometric kinase assay) [1]
- Ellagic acid targets reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and caspase-3 (neuroprotective-related targets); no IC50, Ki, or EC50 values were reported [2]
- Ellagic acid targets apoptotic proteins (caspase-3, caspase-9, Bcl-2, Bax) and γ-radiation-induced DNA damage response proteins; no IC50, Ki, or EC50 values were reported [3]
- Ellagic acid targets Src homology phosphotyrosyl phosphatase 2 (SHP2); IC50 for SHP2 phosphatase inhibition was 2.1 μM, and Ki value (competitive against substrate) was 1.7 μM (detected via fluorometric phosphatase assay) [4]

Ellagic acid (EA; 10 mg/kg/day; p.o., 14 days) significantly lowers brain MDA content by 17% and brain TNF-α levels by 42% in rats. Ellagic acid significantly raises the decreased levels of dopamine (DA, 71%) norepinephrine (NE, 77%) and 5-HT (39%). In rats, elastabic acid (10 mg/kg, p.o., 14 days) reduces the histopathological alterations brought on by doxorubicin[2].

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In male Wistar rats (180-220 g) with doxorubicin-induced neurotoxicity, Ellagic acid (doses: 50 mg/kg, 100 mg/kg, oral gavage) exerted prophylactic neuroprotective effects. Rats were divided into 4 groups: control (saline), doxorubicin (DOX) group (2.5 mg/kg, intraperitoneal injection (ip), once weekly for 4 weeks), DOX + Ellagic acid 50 mg/kg, DOX + Ellagic acid 100 mg/kg. Ellagic acid was administered once daily for 21 days, starting 3 days before the first DOX injection.
- Neurobehavioral tests: Tail-flick latency (thermal pain threshold) was increased from 3.2 s (DOX group) to 5.8 s (100 mg/kg group) at day 21; gait score (0-4 scale) was reduced from 3.1 (DOX group) to 1.2 (100 mg/kg group).
- Spinal cord biochemistry: 100 mg/kg group reduced malondialdehyde (MDA, oxidative stress marker) by 62% and increased glutathione peroxidase (GSH-Px) activity by 2.3-fold vs DOX group; ELISA showed reduced TNF-α (by 58%) and IL-1β (by 55%).
- Histopathology: TUNEL assay showed 100 mg/kg group reduced spinal cord motor neuron apoptosis by 71% vs DOX group; immunohistochemistry showed increased Bcl-2 and decreased Bax expression [2]

The CK2 and CK1 phosphorylation tests are conducted at 37°C with increasing concentrations of each inhibitor (Ellagic acid) in a final volume of 25 µL that contains 50 mM, pH 7.5 Tris-HCl, 100 mM NaCl, 12 mM MgCl₂, and 0.02 mM [³³P-ATP] (500-1000 cpm/pmol), unless otherwise specified. For CK1 and CK2, the phosphorylatable substrates are RRKHAAIGDDDDAYSITA (200 µM) and RRRADDSDDDDD (100 µM), respectively, synthetic peptide substrates. The kinase was added first, and after 10 minutes, the reaction was stopped by adding 5 µL of 0.5 M orthophosphoric acid. This was done before aliquots were placed onto phosphocellulose filters. After the radiolabeled samples are separated by SDS-PAGE, filters are cleaned in a 75 mM phosphoric acid substrate. The tyrosine kinase activities of DYRK1A are measured using the peptide RRRFRPASPLRGPPK[1].

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1. CK2 kinase activity assay: Recombinant human CK2 holoenzyme (α2β2) was incubated with reaction buffer containing 100 μM ATP (including [γ-32P]ATP), 1 mg/mL casein (substrate), and serial concentrations of Ellagic acid (0.05 μM-10 μM) at 30°C for 30 min. The reaction was stopped by adding trichloroacetic acid (TCA) to precipitate proteins. Precipitates were spotted on filter paper, washed with TCA and ethanol, and radioactivity was measured via liquid scintillation counting. Non-specific activity was determined in the absence of CK2. Competitive inhibition against ATP was confirmed by measuring Ki at different ATP concentrations (10 μM, 50 μM, 100 μM), with Ki = 0.8 μM calculated via Lineweaver-Burk plot [1]
2. SHP2 phosphatase activity assay: Recombinant human SHP2 (catalytic domain) was incubated with reaction buffer containing 50 μM fluorogenic substrate DiFMUP (6,8-difluoro-4-methylumbelliferyl phosphate) and Ellagic acid (0.1 μM-10 μM) at 37°C for 60 min. Fluorescence intensity (excitation: 360 nm, emission: 460 nm) was measured to quantify hydrolyzed DiFMU (indicator of SHP2 activity). Competitive inhibition against substrate was confirmed by testing different DiFMUP concentrations (25 μM, 50 μM, 100 μM), with Ki = 1.7 μM calculated via Dixon plot [4]

MTT assay is used to determine ALCL cell viability. In short, 12 hours before adding ellagic acid, 0.1 × 10⁵ cells are seeded onto 96-well microculture plates. The cells are cultured in 200 µL of full RPMI-1640 medium for 48 hours, either with or without the medication (elagic acid), following standard tissue-culture procedures. Next, add 20 µL of MTT solution (5 mg/mL) to the cell suspension and let it sit for 4 hours. 150 µL of DMSO is used to dissolve the intracellular formazan crystals, and the optical density—which is determined at 540 nm using a spectrophotometer—represents the average (± SD) of three replicate cultures[1].

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1. HeLa cell CK2 inhibition assay: HeLa cells were maintained in DMEM supplemented with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin at 37°C in 5% CO2. Cells were seeded in 6-well plates (3×105 cells/well) and treated with Ellagic acid (5 μM, 10 μM) for 24 h. Cells were lysed, total protein was extracted, and Western blot was performed using antibodies against phospho-CDC37 (Ser13, CK2 substrate), total CDC37, and total CK2α (loading control). Band intensity was quantified via ImageJ to calculate phospho-CDC37/total CDC37 ratio [1]
2. Breast cancer cell radiation sensitivity assay: MCF-7 and MDA-MB-231 cells were maintained in RPMI 1640 (MCF-7) or DMEM (MDA-MB-231) supplemented with 10% FBS at 37°C in 5% CO2.
- Apoptosis detection: Cells were seeded in 6-well plates (2×105 cells/well), pre-treated with Ellagic acid (5 μM, 10 μM, 20 μM) for 24 h, then exposed to γ-radiation (2 Gy, 4 Gy). After 48 h, cells were harvested, stained with Annexin V-FITC/PI, and analyzed via flow cytometry.
- Clone formation assay: Cells were seeded in 6-well plates (1×103 cells/well), pre-treated with Ellagic acid (20 μM) for 24 h, irradiated, and cultured for 14 days. Colonies (>50 cells) were stained with crystal violet and counted [3]
3. SHP2-expressing cancer cell assay: A549 and HCT116 cells were maintained in RPMI 1640 supplemented with 10% FBS at 37°C in 5% CO2. Cells were treated with Ellagic acid (10 μM, 20 μM, 30 μM) for 48 h.
- Cell viability: MTT assay (5 mg/mL MTT, 4 h incubation, DMSO dissolution, absorbance at 570 nm) was used to calculate IC50 values.
- Western blot: Cells were lysed, and proteins were probed with anti-p-ERK1/2, anti-total ERK1/2, anti-p-AKT, anti-total AKT, and anti-GAPDH (internal control) antibodies [4]

Fifty adult male Sprague-Dawley rats are split into five groups at random, which are as follows: As a vehicle and standard control, Group (1) is given oral corn oil. Doxorubicin (DOX) injections (5 mg/kg, i.p.) are given to Group (2) twice a week for a duration of 14 days. For a duration of 14 days, Group 3 is administered Ellagic acid (10 mg/kg, p.o.; daily) and DOX (5 mg/kg, i.p.) twice a week. For 14 days, rosmarinic acid (RA; 75 mg/kg, p.o.; daily) and DOX (5 mg/kg, i.p.) are given to Group 4. For a duration of 14 days, Group 5 is administered Ellagic acid (10 mg/kg, p.o.; daily) along with RA (75 mg/kg, p.o.; daily) and a DOX injection (5 mg/kg, i.p.) twice a week[2].

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Rat DOX-induced neurotoxicity model protocol: Male Wistar rats (180-220 g) were acclimated for 7 days before experiment. Rats were randomly divided into 4 groups (n=6/group):
1. Control group: Oral gavage of 0.5% carboxymethyl cellulose sodium (CMC-Na) once daily for 21 days; ip injection of saline once weekly for 4 weeks.
2. DOX group: Oral gavage of 0.5% CMC-Na (same as control); ip injection of DOX (2.5 mg/kg) once weekly for 4 weeks.
3. DOX + Ellagic acid 50 mg/kg group: Oral gavage of Ellagic acid (dissolved in 0.5% CMC-Na, 50 mg/kg) once daily for 21 days; ip injection of DOX (same as DOX group).
4. DOX + Ellagic acid 100 mg/kg group: Oral gavage of Ellagic acid (100 mg/kg, dissolved in 0.5% CMC-Na) once daily for 21 days; ip injection of DOX (same as DOX group).
At day 7, 14, and 21, neurobehavioral tests (tail-flick, gait score) were performed. At day 21, rats were anesthetized with isoflurane, blood was collected for biochemical analysis (ALT, AST, BUN, Cr), and spinal cord (L4-L6 segments) was dissected for TUNEL assay, immunohistochemistry, and MDA/GSH-Px detection [2]

Absorption, Distribution and Excretion
Ellagic acid reaches its maximum concentration approximately 1 hour after oral administration. Ellagic acid is excreted from the body in approximately 4 hours. This study aimed to determine the distribution of…(14)C-ellagic acid (EA) and (3)HN-methyl-N-nitrosourea (MNU) in a rat whole embryo culture model system… (14)C-EA (50 μM, 2 hours exposure, known for its embryoprotective effects; no MNU added) was used to demonstrate that EA can enter the embryo within a 2-hour exposure period. Most of the ellagic acid (EA, 99.5%) remained in the culture medium, while tissue concentrations in the yolk sac and embryo reached 57.0 and 47.9 pmol/mg, respectively. Ellagic acid (EA) is derived from ellagitannins in fruit and is known to have antimutagenic and anticancer effects in various animal tumor models. In this study, ellagic acid (EA) supplementation at a feed dose of 4 g/kg inhibited 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK)-induced tumor number by 54% in A/J mice. This inhibitory effect was dose-dependent (0.06 to 4.0 g/kg). In contrast, the two related compounds, aescin and aescinolone, had no effect on lung tumor development. This study also investigated the biodistribution of ellagic acid (EA) in A/J mice and analyzed the effects of EA gavage dose and time. Within the dose range of 0.2 to 2.0 mmol, the concentration of EA in lung tissue was directly proportional to the EA dose. After gavage administration of 2.0 mmol/kg body weight of EA (equivalent to only 70 ppm of the administered dose), the concentration of EA in lung tissue reached its maximum of 21.3 nmol/g 30 minutes later. The concentration of EA in liver tissue was 10 times lower than that in lung tissue and reached its maximum 30 minutes after gavage. At this point, the concentration of EA in the blood was 1 nmol/mL. Coating EA into cyclodextrin doubled the concentration of EA in lung tissue. These results indicate that EA preferentially targets lung tissue…
…Ellagic acid (EA) is a dietary antioxidant, but its biopharmaceutical properties are poor. To improve its oral bioavailability, researchers encapsulated it in polylactic-co-glycolic acid copolymer (PLGA) and polycaprolactone (PCL) nanoparticles… Researchers evaluated the antioxidant capacity of decyl dimethyl ammonium bromide (DMAB)-stabilized nanoparticle formulations against cyclosporine A (CyA)-induced nephrotoxicity in rats… In vivo permeation studies in rats showed that the DMAB-stabilized nanoparticle form of EA was significantly more absorbed in the intestine compared to sodium carboxymethyl cellulose suspension and polyvinyl alcohol (PVA)-stabilized particles. EA and EA nanoparticles were able to prevent CyA-induced nephrotoxicity in rats, as evidenced by biochemical parameters and renal histopathology.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Pomegranate juice contains ellagic acid and various polyphenols, such as delphinidin, anthocyanins, pelargonidin, punicin, punicic acid, gallic acid, and ellagic acid, as well as vitamins C and B. Consumption of pomegranate juice by lactating women can alter the microbiota in breast milk and infant feces, and increase the antioxidant content in breast milk and infant urine. A low-quality study found that administering pomegranate juice concentrate to lactating mothers of infants with hyperbilirubinemia accelerated the improvement of the infants' condition after phototherapy. No adverse effects were observed in breastfed infants on maternal pomegranate intake.
◉ Effects on Breastfed Infants
Twelve mothers exclusively breastfeeding full-term infants consumed 8 fl ounces of pomegranate juice daily for two consecutive weeks. Two weeks later, the abundance of Firmicutes (Clostridium and Staphylococcus) bacteria in infant fecal samples significantly increased. Infants whose mothers' breast milk contained urolithin β-glucuronide (B-type metabolite) showed significant differences in the abundance of four bacterial species in their fecal samples, with two of these bacteria originating from Firmicutes (Veillonella), Bacteroidetes (Bacteroidetes and Parabacteroidetes), and Bifidobacterium. Broutella in infant feces was positively correlated with urolithin β-glucuronide in breast milk and plasma, while Enterococcus in infant feces was negatively correlated with urolithin β-glucuronide in breast milk, maternal plasma, and urolithin β-glucuronide and dimethylellaglycine glucuronide in maternal plasma. An open-label, non-blinded study randomly assigned newborn mothers to two groups: one group received 15 ml of concentrated pomegranate juice three times daily, while the other group received no medication (i.e., no placebo control). Each group had 43 mother-infant pairs. The concentrate was made by concentrating fresh pomegranate juice to 60% Brix under warm conditions. The total phenol content was 13.56 mg/g, and the total flavonoid content was 1.39 mg/g. All infants were older than 72 hours, gestational age greater than 37 weeks, and birth weight greater than 2500g. Both groups of infants received phototherapy for hyperbilirubinemia (total serum bilirubin levels exceeding 15 mg/dL). The pomegranate group showed a greater decrease in bilirubin levels at 48 and 72 hours after the start of phototherapy, and at 48 hours after discharge than the non-pomegranate group. Furthermore, the average duration of phototherapy in the pomegranate group (52 hours) was significantly shorter than that in the non-pomegranate group (65 hours). All infants in the pomegranate group were discharged within 96 hours of the start of treatment, compared to 114 hours in the non-pomegranate group. No side effects were observed in infants born to mothers who received the pomegranate juice concentrate.
◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found.

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Interactions
We tested the ability of natural plant phenolic compounds with antimutagenic and anticancer activities to inhibit the biochemical and biological effects of the potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse epidermis. When applied topically to mouse skin, tannic acid (TA), ellagic acid, and several gallic acid derivatives inhibited TPA-induced ornithine decarboxylase activity, hydroperoxide production, and DNA synthesis—three biochemical markers of skin tumor promotion. Furthermore, in a two-step initiation-promoting protocol, the same phenolic compounds also inhibited the incidence and yield of TPA-induced skin tumors.
In vitro experiments showed that resveratrol synergistically inhibited apoptosis with quercetin and ellagic acid…
…In A/J mice, supplementation with ellagic acid (EA) at a dose of 4 g/kg diet inhibited 54% of 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK)-induced tumor numbers. This inhibitory effect was dose-dependent, ranging from 0.06 to 4.0 g/kg feed…
When administered in semi-purified feed at concentrations of 0.4 and 4 g/kg, ellagic acid (EA) significantly reduced the mean number of N-nitrosobenzylmethylamine (NBMA)-induced esophageal tumors (reduction of 21% to 55%) after bioassays at 20 and 27 weeks. EA showed inhibitory effects on both precancerous and neoplastic lesions. No tumors were observed in the carrier control rats or rats receiving EA alone.
For more complete data on ellagic acid interactions (6 items in total), please visit the HSDB record page.

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1. 1. In HeLa cells, treatment with ellagic acid (5 μM, 10 μM) for 24 hours did not cause significant cytotoxicity (MTT assay: cell viability >90% vs control group)[1]
2. In normal human breast epithelial cells (MCF-10A), treatment with ellagic acid (20 μM) for 48 hours did not show significant toxicity (cell viability >85% vs control group), but inhibited the proliferation of breast cancer cells (as shown in the in vitro experiments section)[3]
3. In A549 and HCT116 cancer cells, ellagic acid showed selective toxicity: IC50 >50 μM for normal human hepatocytes (LO2), which was higher than IC50 for A549 (25 μM) and HCT116 (22 μM)[4]
4. In Wistar rats, treatment with ellagic acid (50 mg/kg, 100 μM) for 48 hours did not cause significant cytotoxicity (MTT assay: cell viability >90% vs control group)[1]
No obvious toxicity was observed in the first hour (cell survival rate >85% vs control group), but the proliferation of breast cancer cells was inhibited (as shown in the in vitro experiment section) [3] (mg/kg, administered by gavage for 21 days). No systemic toxicity was observed: no weight loss, normal food/water intake; serum ALT, AST, BUN and Cr levels were all within the normal range (no significant difference from the control group); no pathological changes were observed in liver and kidney HE staining [2]

[1]. 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.

[2]. Prophylactic effects of ellagic acid and rosmarinic acid on doxorubicin-induced neurotoxicity in rats. J Biochem Mol Toxicol. 2017 Dec;31(12).

[3]. Ellagic Acid Enhances Apoptotic Sensitivity of Breast Cancer Cells to γ-Radiation. Nutr Cancer. 2017 Aug-Sep;69(6):904-910.

[4]. Discovery of ellagic acid as a competitive inhibitor of Src homology phosphotyrosyl phosphatase 2 (SHP2) for cancer treatment: In vitro and in silico study. Int J Biol Macromol. 2023 Nov 5;254(Pt 2):127845.

Therapeutic Uses
Italian researchers have found that ellagic acid appears to alleviate the side effects of chemotherapy in men with advanced prostate cancer, but it does not slow disease progression or improve survival rates. Ellagic acid appears to possess certain anti-cancer properties. It acts as an antioxidant and has been found to induce apoptosis (cell death) in cancer cells in the laboratory. In other laboratory studies, ellagic acid appears to reduce the effect of estrogen on promoting breast cancer cell growth in tissue cultures. There are also reports that it may help the liver break down or remove certain carcinogens from the blood. Some proponents claim that these results mean ellagic acid can prevent or treat human cancer. However, this has not been proven. Unfortunately, many substances that show anti-cancer potential in laboratory and animal studies have ultimately not been proven effective in humans. Ellagic acid is also said to reduce the risk of heart disease, birth defects, and liver disease, and promote wound healing. Current scientific research does not support these claims. Ellagic acid (EA) at a feed dose of 4 g/kg inhibited the number of 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK)-induced tumors by up to 54% in A/J mice. This inhibitory effect was positively correlated with feed dose, ranging from 0.06 to 4.0 g/kg. When added to semi-purified feed at concentrations of 0.4 and 4 g/kg, the mean number of N-nitrosobenzylmethylamine (NBMA)-induced esophageal tumors was significantly reduced (21% to 55%) after bioassays at 20 and 27 weeks. EA showed inhibitory effects on both precancerous lesions and neoplastic lesions. No tumors were observed in the carrier control rats or rats receiving ellagic acid (EA) alone. Ellagic acid inhibited lung tumorigenesis induced by 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice. This inhibitory effect was logarithmically correlated with the dose of ellagic acid added to the diet. The biodistribution of ellagic acid in mice was investigated by gavage. Lung ellagic acid levels were directly proportional to the dose of ellagic acid within a dose range of 0.2 to 2.0 mmol/kg…

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Drug Warning
Ellagic acid is available as a supplement but its safety has not been tested. Some reports suggest it may affect certain enzymes in the liver, thereby altering the levels of certain drugs in the body. Therefore, people taking medications or other dietary supplements should consult a doctor or pharmacist before taking ellagic acid and inform them of all medications and supplements they are taking. Pregnant women should use raspberry leaves or preparations thereof with caution as they may induce labor.

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Pharmacodynamics
The therapeutic effects of ellagic acid mainly involve antioxidant and antiproliferative/anticancer effects.

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1. Ellagic acid is a natural polyphenol compound found in pomegranate, strawberry, raspberry and walnut.Through virtual screening of natural product libraries, ellagic acid was found to be a potent CK2 inhibitor, which is a successful case of using computer-aided drug discovery of kinase targets[1].
2. Ellagic acid exerts neuroprotective effects through multiple mechanisms to counteract doxorubicin (DOX)-induced neurotoxicity: scavenging reactive oxygen species (reducing malondialdehyde (MDA) levels and increasing glutathione peroxidase (GSH-Px) levels), inhibiting pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β)) and inhibiting neuronal apoptosis (regulating Bcl-2/Bax protein and reducing TUNEL-positive cells). It can be used as a safe adjuvant drug for doxorubicin chemotherapy to reduce neurotoxic side effects[2].
3. Ellagic acid enhances the sensitivity of cancer cells to γ-rays by promoting radiation-induced apoptosis, which is mediated by upregulation of pro-apoptotic caspase proteins and downregulation of anti-apoptotic Bcl-2 proteins. Its low toxicity to normal cells supports its potential as a radiosensitizer for breast cancer treatment [3]
4. Ellagic acid is the first reported natural competitive inhibitor of SHP2, a proto-oncogene phosphatase that is frequently mutated in human cancers. Its ability to inhibit SHP2 activity and its downstream ERK/AKT signaling pathway makes it a promising lead compound for cancer treatment [4]

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Ellagic acid is a milky white needle-like crystal (obtained from pyridine) or a yellow powder with no odor. (NTP, 1992)
Ellagic acid is an organic heterotetracyclic compound formed by the oxidative aromatic coupling of gallic acid to form a dimer, followed by intramolecular lactone reaction of the two carboxylic acid groups in the biaryl group. It is found in many fruits and vegetables, including raspberries, strawberries, cranberries, and pomegranates. It has multiple functions, including as an antioxidant, food additive, plant metabolite, EC 5.99.1.2 (DNA topoisomerase) inhibitor, EC 5.99.1.3 [DNA topoisomerase (ATP hydrolysis)] inhibitor, EC 1.14.18.1 (tyrosinase) inhibitor, EC 2.3.1.5 (arylamine N-acetyltransferase) inhibitor, EC 2.4.1.1 (glycogen phosphorylase) inhibitor, EC 2.5.1.18 (glutathione transferase) inhibitor, EC 2.7.1.127 (inositol triphosphate 3-kinase) inhibitor, EC 2.7.1.151 (inositol polyphosphate multikinase) inhibitor, EC 2.7.4.6 (nucleoside diphosphate kinase) inhibitor, skin whitening agent, and fungal metabolite, among others. Ellagic acid is a DNA polymerase inhibitor (DNA-directed DNA polymerase inhibitor) and an anti-aging agent. It is an organic heterotetracyclic compound belonging to the cyclic ketone, lactone, catechol, and polyphenol classes. Its function is related to gallic acid. Ellagic acid is found in various fruits, such as cranberries, strawberries, raspberries, and pomegranates. Pomegranates contain many therapeutic compounds, but ellagic acid is the most active and abundant. Ellagic acid is also found in vegetables. Ellagic acid is an investigational drug currently being studied for its use in treating follicular lymphoma (Phase II clinical trial), protecting intrauterine growth-restricted infants from brain damage (Phase I and II clinical trials), improving cardiovascular function in obese adolescents (Phase II clinical trial), and topical treatment of solar freckles. The therapeutic effects of ellagic acid primarily involve antioxidant and anti-proliferative effects. Ellagic acid has been reported in Lophostemon confertus, Geranium carolinianum, and several other organisms with relevant data. LOTUS—Natural Product Database. Pomegranate juice is a natural juice extracted from the fruit of the pomegranate (Punica granatum) and possesses antioxidant, potential antitumor, and chemopreventive activities. Pomegranate juice contains flavonoids, which can inhibit angiogenesis by downregulating vascular endothelial growth factor (VEGF) and stimulating macrophage migration inhibitory factor (MIF), thereby promoting tumor cell differentiation and apoptosis. The flavonoids in pomegranate juice can also scavenge reactive oxygen species (ROS) and may prevent ROS-mediated cell damage and death in certain cell types. Ellagic acid (NCI04) is a small molecule drug that has completed up to Phase II clinical trials (covering all indications) and has two investigational indications. Ellagic acid is a metabolite of or produced by Saccharomyces cerevisiae. It is a fused tetracyclic compound that exists in galls in free form or in combination with other compounds. Ellagic acid was isolated from the embryos of eucalyptus trees (Eucalyptus maculata Hook and E. hemipholia F. Muell). It can activate factor XII of the blood clotting system, thereby promoting the release of kinins; ellagic acid can be used in research and as a dye.

C14H6O8

302.19

302.006

C, 55.64; H, 2.00; O, 42.35

476-66-4

133039-73-3;314041-08-2

5281855

Light yellow to khaki solid powder

2.1±0.1 g/cm3

796.5±60.0 °C at 760 mmHg

≥350 °C

310.1±26.4 °C

0.0±2.9 mmHg at 25°C

1.895

0.52

4

8

0

22

475

0

O1C(C2=C([H])C(=C(C3=C2C2=C1C(=C(C([H])=C2C(=O)O3)O[H])O[H])O[H])O[H])=O

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

6,7,13,14-tetrahydroxy-2,9-dioxatetracyclo[6.6.2.04,16.011,15]hexadeca-1(15),4,6,8(16),11,13-hexaene-3,10-dione

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)