punicalin and punicalagin

Ellagitannins are literally a class of tannins. Triggered by the oxidation of the phenolic parts on β-pentagalloyl-d-glucose, ellagitannins are generated through various structural conversions, such as the coupling of the phenolic parts, oxidation to highly complex structures, and the formation of dimer and lager analogs, which expand the structural diversity. To date, more than 1000 natural ellagitannins have been identified. Since these phenolic compounds exhibit a variety of biological activities, ellagitannins have potential applications in medicine and health enhancement. Within the context of identifying suitable applications, considerations need to be based on correct structural features. This review describes the structural revisions of 32 natural ellagitannins, namely alnusiin; alnusnin A and B; castalagin; castalin; casuarinin; cercidinin A and B; chebulagic acid; chebulinic acid; corilagin; geraniin; isoterchebin; nobotanin B, C, E, G, H, I, J, and K; punicalagin; punicalin; punigluconin; roxbin B; sanguiin H-2, H-3, and H-6; stachyurin; terchebin; vescalagin; and vescalin. The major focus is on the outline of the initial structural determination, on the processes to find the errors in the structure, and on the methods for the revision of the structure.

Topics: Benzopyrans; Glucosides; Hydrolyzable Tannins; Molecular Structure; Oxidation-Reduction; Phenols; Terminology as Topic

Globally, breast cancer represents serious cause of morbidity and mortality. Our goal is to improve nutraceuticals that have the ability to overlap the side effects of conventional therapies and promising tumoricidal effects by using nanotechnology techniques. The current work was premeditated to explore the apoptotic effects of punicalin (PN) and punicalagin (PNG) nano-prototypes, derived from Punica granatum, on human breast cancerous MCF7 and MDA-MB-231 cells in vitro.. Firstly, we prepared and characterized of PN, PGN, and 5-flurouracil (FU)-loaded PLGA, PLGA-coated-CS, and PLGA-coated-CS-PEG nano-prototypes. Then, we studied the toxicological and biochemical effects of all nanoformulations. Finally, we measured the genetic and protein expression levels of apoptotic and survival candidates in cancer cells.. Our results showed that the newly synthesized nano-prototypes had cytotoxic and apoptotic effects on MCF7 and MDA-MB-231 cell lines. Moreover, they up-regulated Bax and Cas-3 expression levels, as well as down-regulated BCL-2, NF-ĸB and PI3k expression levels compared to control. Nitric oxide (NO) and zinc (Zn) levels were significantly elevated (P < 0.05) after the application of PN and PNG nano-prototypes compared to the control.. PN and PNG nano-prototypes of PLGA decorated with CS and PEG enhanced the anti-cancer activity through induction of cytotoxicity, reactive oxygen species (ROS)-mediated apoptosis.

Topics: Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Female; Humans; Hydrolyzable Tannins; Reactive Oxygen Species

Our recent study has shown that pomegranate peel extract (PEx) showed significant immunomodulatory activity, which might be caused by ellagitannins. The aim of this work was to test the hypothesis that ellagitannin components act synergistically in the modulation of cytokine production.. Human peripheral blood mononuclear cells (PBMCs) from healthy donors were stimulated with phytohemagglutinin and treated with different concentrations of PEx or punicalagin (PG), punicalin (PN), and ellagic acid (EA), alone or with their combinations. Cytotoxicity, cell proliferation, and cytokine production were determined.. Non-cytotoxic concentrations of all compounds significantly inhibited cell proliferation. IC50 values (μg/mL) were: EA (7.56), PG (38.52), PEx (49.05), and PN (69.95). PEx and all ellagitannins inhibited the levels of TNF-α, IL-6, and IL-8, dose-dependently, and their combinations acted synergistically. PEx and all ellagitannins inhibited Th1 and Th17 responses, whereas the lower concentrations of PEx stimulated the production of IL-10, a Treg cytokine, as did lower concentrations of EA. However, neither component of ellagitannins increased Th2 response, as was observed with PEx.. The combination of PG, PN, and EA potentiated the anti-inflammatory response without any significant synergistic down-modulatory effect on T-cell cytokines. The increased production of IL-10 observed with PEx could be attributable to EA, but the examined ellagitannins are not associated with the stimulatory effect of PEx on Th2 response.

Topics: Cytokines; Ellagic Acid; Humans; Hydrolyzable Tannins; Interleukin-10; Leukocytes, Mononuclear; Lythraceae; Plant Extracts; Pomegranate

The ethanol extract of Punica granatum L. rind was tested to show significant nematicidal activity against pine wood nematode. Three nematicidal compounds were obtained from the ethanol extract by bioassay-guided fractionation and identified as punicalagin 1, punicalin 2, and corilagin 3 by mass and nuclear magnetic resonance spectral data analysis. Punicalagin 1 was most active against PWN among the purified compounds with the LC

Topics: Acetylcholinesterase; Amylases; Animals; Antinematodal Agents; Cellulase; Cholinesterase Inhibitors; Glucosides; Hydrolyzable Tannins; Lythraceae; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Plant Extracts; Tylenchida

Our research group has found preliminary evidences of the fungal biodegradation pathway of ellagitannins, revealing first the existence of an enzyme responsible for ellagitannins degradation, which hydrolyzes pomegranate ellagitannins and it was called ellagitannase or elagitannin acyl hydrolase. However, it is necessary to generate new and clear information in order to understand the ellagitannin degradation mechanisms. This work describes the distinctive and unique features of ellagitannin metabolism in fungi. In this study, hydrolysis of pomegranate ellagitannins by Aspergillus niger GH1 was studied by solid-state culture using polyurethane foam as support and pomegranate ellagitannins as substrate. The experiment was performed during 36 h. Results showed that ellagitannin biodegradation started after 6 h of fermentation, reaching the maximal biodegradation value at 18 h. It was observed that ellagitannase activity appeared after 6 h of culture, then, the enzymatic activity was maintained up to 24 h of culture reaching 390.15 U/L, after this period the enzymatic activity decreased. Electrophoretic band for ellagitannase was observed at 18 h. A band obtained using non-denaturing electrophoresis was identified as ellagitannase, then, a tandem analysis to reveal the ellagitannase activity was performed using Petri plate with pomegranate ellagitannins. The extracts were analyzed by HPLC/MS to evaluate ellagitannins degradation. Punicalin, gallagic acid, and ellagic acid were obtained from punicalagin. HPLC/MS analysis identified the gallagic acid as an intermediate molecule and immediate precursor of ellagic acid. The potential application of catabolic metabolism of ellagitannin hydrolysis for ellagic acid production is outlined.

Topics: Aspergillus niger; Biodegradation, Environmental; Bioreactors; Ellagic Acid; Enzyme Activation; Fermentation; Hydrolyzable Tannins; Lythraceae; Metabolic Networks and Pathways; Plant Extracts

The development of new agents to target HBV cccDNA is urgently needed because of the limitations of current available drugs for treatment of hepatitis B. By using a cell-based assay in which the production of HBeAg is in a cccDNA-dependent manner, we screened a compound library derived from Chinese herbal remedies for inhibitors against HBV cccDNA. Three hydrolyzable tannins, specifically punicalagin, punicalin and geraniin, emerged as novel anti-HBV agents. These compounds significantly reduced the production of secreted HBeAg and cccDNA in a dose-dependent manner in our assay, without dramatic alteration of viral DNA replication. Furthermore, punicalagin did not affect precore/core promoter activity, pgRNA transcription, core protein expression, or HBsAg secretion. By employing the cell-based cccDNA accumulation and stability assay, we found that these tannins significantly inhibited the establishment of cccDNA and modestly facilitated the degradation of preexisting cccDNA. Collectively, our results suggest that hydrolyzable tannins inhibit HBV cccDNA production via a dual mechanism through preventing the formation of cccDNA and promoting cccDNA decay, although the latter effect is rather minor. These hydrolyzable tannins may serve as lead compounds for the development of new agents to cure HBV infection.

Topics: Antiviral Agents; DNA Replication; DNA, Circular; DNA, Viral; Drug Discovery; Drugs, Chinese Herbal; Glucosides; Hepatitis B; Hepatitis B e Antigens; Hepatitis B virus; Hydrolyzable Tannins; Small Molecule Libraries; Virus Replication

Hepatitis C virus (HCV) is the causative agent of end-stage liver disease. Recent advances in the last decade in anti HCV treatment strategies have dramatically increased the viral clearance rate. However, several limitations are still associated, which warrant a great need of novel, safe and selective drugs against HCV infection. Towards this objective, we explored highly potent and selective small molecule inhibitors, the ellagitannins, from the crude extract of Pomegranate (Punica granatum) fruit peel. The pure compounds, punicalagin, punicalin, and ellagic acid isolated from the extract specifically blocked the HCV NS3/4A protease activity in vitro. Structural analysis using computational approach also showed that ligand molecules interact with the catalytic and substrate binding residues of NS3/4A protease, leading to inhibition of the enzyme activity. Further, punicalagin and punicalin significantly reduced the HCV replication in cell culture system. More importantly, these compounds are well tolerated ex vivo and'no observed adverse effect level' (NOAEL) was established upto an acute dose of 5000 mg/kg in BALB/c mice. Additionally, pharmacokinetics study showed that the compounds are bioavailable. Taken together, our study provides a proof-of-concept approach for the potential use of antiviral and non-toxic principle ellagitannins from pomegranate in prevention and control of HCV induced complications.

Topics: Animals; Antiviral Agents; Cell Line, Tumor; Chromatography, High Pressure Liquid; Ellagic Acid; Hepacivirus; Hepatitis C; Host-Pathogen Interactions; Humans; Hydrolyzable Tannins; Lythraceae; Mass Spectrometry; Mice, Inbred BALB C; Models, Molecular; Molecular Structure; Phytotherapy; Protein Binding; Small Molecule Libraries; Viral Nonstructural Proteins; Virus Replication

The cytochrome P450 enzyme, CYP1B1, is an established target in prostate cancer chemoprevention. Compounds inhibiting CYP1B1 activity are contemplated to exert beneficial effects at three stages of prostate cancer development, that is, initiation, progression, and development of drug resistance. Pomegranate ellagitannins/microbial metabolites were examined for their CYP1B1 inhibitory activity in a recombinant CYP1B1-mediated ethoxyresorufin-O-deethylase (EROD) assay. Urolithin A, a microbial metabolite, was the most potent uncompetitive inhibitor of CYP1B1-mediated EROD activity, exhibiting 2-fold selectivity over CYP1A1, while urolithin B was a noncompetitive inhibitor with 3-fold selectivity. The punicalins and punicalagins exhibited potent CYP1A1 inhibition with 5-10-fold selectivity over CYP1B1. Urolithins, punicalins, and punicalagins were tested for their 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced CYP1 inhibitory activity in the 22Rv1 prostate cancer cell line. Urolithins A and B showed a decrease in their CYP1-mediated EROD inhibitory IC50 values upon increasing their treatment times from 30 min to 24 h. Urolithin C, 8-O-methylurolithin A, and 8,9-di-O-methylurolithin C caused a potent CYP1-mediated EROD inhibition in 22Rv1 cells upon 24 h of incubation. Neutral red uptake assay results indicated that urolithin C, 8-O-methylurolithin A, and 8,9-di-O-methylurolithin C induced profound cytotoxicity in the proximity of their CYP1 inhibitory IC50 values. Urolithins A and B were studied for their cellular uptake and inhibition of TCDD-induced CYP1B1 expression. Cellular uptake experiments demonstrated a 5-fold increase in urolithin uptake by 22Rv1 cells. Western blots of the CYP1B1 protein indicated that the urolithins interfered with the expression of CYP1B1 protein. Thus, urolithins were found to display a dual mode mechanism by decreasing CYP1B1 activity and expression.

Topics: Anticarcinogenic Agents; Aryl Hydrocarbon Hydroxylases; Colon; Coumarins; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP1B1; Enzyme Inhibitors; Fruit; Humans; Hydrolyzable Tannins; Lythraceae; Male; Prostatic Neoplasms; Recombinant Proteins

This study analyzes the major phenolic constituents of pomegranate fruit juice and pericarp feedstock, and dry extracts thereof, using high-performance liquid chromatography. Pomegranate pericarp was extracted with water (WE) and alcohol (AE) as solvents, and liquid extracts were subsequently freeze-dried. The results indicate that ellagitannins punicalagin A and punicalagin B are the major constituents in the primary pomegranate feedstock and in both types of extracts. Ellagic acid, a common botanical constituent that is currently used to standardize pomegranate extracts, as well as ellagitannin punicalin, were found to be only minor constituents. Total punicalagins (the sum of punicalagins A+B and punicalin) and ellagic acid content in the pomegranate fruit pericarp feedstock WE were 7,6+/-0,3% and 0,2+/-0,1% by dry weight, respectively, and in the AE feedstock 7,0+/-0,2 and 0,4+/-0,1%, respectively. Total phenolic content (the sum of punicalagins and ellagic acid) in the pomegranate WE and AE were 45,8+/-1,2% and 42,3+/-1,1%, respectively. The concentrations of ellagic acid in the pomegranate WE and AE were 0,8+/-0,2% and 3,9+/-0,2%, respectively. Total phenolics in fresh single-strength pomegranate whole fruit juice contained 2,216+/-70 mg/L (95% punicalagins), whereas commercial pomegranate juice that was purchased from local stores was 317+/-13 mg/L (70% punicalagins). Our results strongly suggest that the commercially produced pomegranate extracts should be standardized to the content of total punicalagins as well as ellagic acid. The current standard uses only ellagic acid, which is unreliable, potentially misleading and vulnerable to commercial adulteration.

Topics: Chromatography, High Pressure Liquid; Ellagic Acid; Health Promotion; Humans; Hydrolyzable Tannins; In Vitro Techniques; Lythraceae; Phytotherapy; Plant Extracts

Punicalagin and punicalin were isolated from the leaves of Terminalia catappa L., a Combretaceous plant distributed throughout tropical and subtropical beaches, which is used for the treatment of dermatitis and hepatitis. Our previous studies showed that both of these compounds exert antioxidative activity. In this study, the antihepatotoxic activity of punicalagin and punicalin on acetaminophen-induced toxicity in the rat liver was evaluated. After evaluating the changes of several biochemical functions in serum, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were increased by acetaminophen administration and reduced by punicalagin and punicalin. Histological changes around the hepatic central vein and oxidative damage induced by acetaminophen were also recovered by both compounds. The data show that both punicalagin and punicalin exert antihepatotoxic activity, but treatment with larger doses enhanced liver damage. These results suggest that even if punicalagin and punicalin have antioxidant activity at small doses, treatment with larger doses will possibly induce some cell toxicities.

Topics: Acetaminophen; Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Hydrolyzable Tannins; Lipid Peroxidation; Liver; Liver Diseases; Male; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar; Rosales; Tannins

Punicalagin and punicalin were isolated from the leaves of Terminalia catappa L. In this study, we evaluated the anti-inflammatory activity of punicalagin and punicalin carrageenan-induced hind paw edema in rats. After evaluation of the anti-inflammatory effects, the edema rates were increased by carrageenan administration and reduced by drug treatment. After 4 hr of carrageenan administration, the best effect group was the punicalagin (10 mg/kg) treated group (inhibition rate was 58.15%), and the second was the punicalagin (5 mg/kg)-treated group (inhibition rate was 39.15%). However, even if the anti-inflammatory activity of punicalagin was the same as punicalin at the 5 mg/kg dose, the inhibition effect from larger doses of punicalagin was increased, but there was a decrease with a larger dose of punicalin. The data showed that both punicalagin and punicalin exert anti-inflammatory activity, but treatment with larger doses of punicalin may induce some cell damages.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Carrageenan; Hydrolyzable Tannins; Indomethacin; Inflammation; Kinetics; Male; Rats; Rats, Inbred WKY; Tannins

Punicalagin and punicalin, isolated from the leaves of Terminalia catappa L., are used to treat dermatitis and hepatitis. Both compounds have strong antioxidative activity. The antihepatotoxic activity of punicalagin and punicalin on carbon tetrachloride (CCl4)-induced toxicity in the rat liver was evaluated. Levels of serum glutamate-oxalate-transaminase and glutamate-pyruvate-trans-aminase were increased by administration of CCl4 and reduced by drug treatment. Histological changes around the liver central vein and oxidation damage induced by CCl4 also benefited from drug treatment. The results show that both punicalagin and punicalin have anti-hepatotoxic activity but that the larger dose of punicalin induced liver damage. Thus even if tannins have strong antioxidant activity at very small doses, treatment with a larger dose will induce cell damage.

Topics: Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Carbon Tetrachloride Poisoning; Dose-Response Relationship, Drug; Hydrolyzable Tannins; Lipid Peroxidation; Liver; Male; Plant Leaves; Plants, Medicinal; Rats; Rats, Wistar; Reactive Oxygen Species; Taiwan; Tannins