Pomegranate Juice Consumption Research Articles

Effects of pomegranate juice consumption on blood pressure and lipid profile in patients with type 2 diabetes: A single-blind randomized clinical trial

Pomegranate juice (PJ) has abundant anti-oxidative polyphenolic compounds which are assumed to have cardioprotective effects such as hypotensive properties. This study aimed to investigate the effects of PJ consumption on blood pressure and lipid profile F variables in patients with type 2 diabetes. Sixty subjects (30 in intervention group and 30 in control group) were recruited in this single-blind placebo-controlled randomized clinical trial. The volunteers were randomly assigned to one of two groups. Treatment group consumed 200 ml/day PJ for 6 weeks, while control group received no intervention. Systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) concentrations were measured following 12-14h of fasting at baseline and at the end of the study. After 6 weeks of intervention, SBP (13.5±1.5mmHg vs. 12.3±2.5, P<0.001) and DBP (7.7±1.6 vs. 7.2±1.6mmHg, P<0.05) significantly decreased in the intervention group. Similarly, SBP and DBP in the intervention group were significantly lower than the control group after intervention (P<0.02 and P<0.03, respectively). At the end of the intervention, TC, TG, LDL-C and HDL-C did not significantly differ between the intervention group and the control group however, TC and LDL-C decreased significantly compared to pre-trial values within the intervention group. It is concluded that PJ consumption could decrease systolic and diastolic blood pressure in patients with diabetes while having no effect on lipid profile. A more definitive result will be obtained if future studies could conducted in hyperlipidemic individuals who might be more prone to respond to the lipid-lowering effects.

Pomegranate Juice Increases Sirtuin1 Protein in Peripheral Blood Mononuclear Cell from Patients with Type 2 Diabetes: A Randomized Placebo Controlled Clinical Trial.

Few studies have examined anti-inflammatory effects of pomegranate juice (PJ). The present study aimed to evaluate the effect of PJ on nuclear factor kappa B (NF-κB) p65 and sirtuin1 in peripheral blood mononuclear cell (PBMC), and plasma vascular inflammation biomarkers. Patients with type 2 diabetes were randomly assigned to either the PJ (n = 22) or the placebo group (n = 22). The patients in the PJ group received 250 mL of PJ daily for 12 weeks, whereas the placebo group received corresponding control beverages of similar color and energy content. At baseline and at the end of week 12, fasting plasma concentrations of soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), and soluble E-selectin (sE-selectin) were measured. NF-κB p65 and SIRT1 were measured in the PBMC. Plasma sE-selectin concentration decreased significantly in the PJ group at the end of week 12 compared to baseline (P < 0.001 for treatment effect), and the reduction was significant in comparison with the placebo group (P < 0.05 for treatment effect). There were no significant differences between the two groups in plasma sICAM-1 and sVCAM-1. At the end of the study, compared with the placebo group, NF-κB p65 in PBMC was significantly lower (P < 0.01 for treatment effect) and SIRT1 was significantly higher (P < 0.0001 for treatment effect) in the PJ group. This study supports the PJ consumption as a food with potential benefits in individuals with type 2 diabetes as evidenced by improvements in NF-κB and SIRT1 levels in PBMC of study participants.

Antenatal pomegranate juice rescues hypoxia-induced fetal growth restriction in pregnant mice while reducing placental cell stress and apoptosis

IntroductionThere is a need for prophylaxis to reduce placental-associated intrauterine growth restriction (IUGR). Pomegranate juice (PJ) is replete with phytochemicals having biological effects at non-pharmacological concentrations. We test the hypothesis that exposure of pregnant mice to hypoxia late in gestation induces cellular stress in the placenta, which can be ameliorated by antecedent maternal consumption of PJ. Materials and methodsWe exposed pregnant mice to 12% or 21% oxygen, with food ad libitum or restricted, and with consumption of PJ or glucose between 12.5 and 18.5 days post conception (dpc). We examined the outcomes of the nine groups (n = 10) at 18.5 dpc, quantifying fetal and placental weights and placental labyrinthine and junctional zone depths and areas. We assayed cellular stress by expression of Hsp90 and apoptosis by TUNEL staining and expression of cleaved caspase 3. ResultsMaternal exposure to 12% oxygen or food restriction in 21% oxygen, induced IUGR, compared to control. The labyrinth to junctional zone ratio was lower in hypoxic ad libitum, compared to normoxic food-restricted, placentas. Antenatal PJ prior to and during hypoxic exposure significantly improved fetal growth, reduced Hsp90 expression, and limited apoptosis in the labyrinth, while enhancing junctional zone apoptosis. DiscussionMaternal exposure to hypoxia induces IUGR, cell stress, and apoptosis in mouse placentas. The labyrinth and junctional zone of the mouse placenta are differentially sensitive to FiO2 and to PJ. PJ offers benefits in the prophylaxis of IUGR in the mouse, but PJ effects on the junctional zone require further study.

Could Pomegranate Juice Help in the Control of Inflammatory Diseases?

Fruits rich in polyphenols, such as pomegranates, have been shown to have health benefits relating to their antioxidant and anti-inflammatory properties. Using data obtained from PubMed and Scopus, this article provides a brief overview of the therapeutic effects of pomegranate on chronic inflammatory diseases (CID) such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), metabolic and cardiovascular disorders, and other inflammatory-associated conditions, with an emphasis on fruit-derived juices. Most studies regarding the effects of pomegranate juice have focused on its ability to treat prostate cancer, diabetes, and atherosclerosis. However, pomegranate juice has shown therapeutic potential for many other illnesses. For instance, a small number of human clinical trials have highlighted the positive effects of pomegranate juice and extract consumption on cardiovascular health. The beneficial effects of pomegranate components have also been observed in animal models for respiratory diseases, RA, neurodegenerative disease, and hyperlipidaemia. Furthermore, there exists strong evidence from rodent models suggesting that pomegranate juice can be used to effectively treat IBD, and as an anti-inflammatory agent to treat CID. The effects of pomegranate intake should be further investigated by conducting larger and more well-defined human trials.

Effect of pomegranate juice consumption on biochemical parameters and complete blood count.

Pomegranate has been used therapeutically for centuries. The aim of the present study was to examine the effects of pomegranate juice (PJ) supplementation on complete blood count (CBC), glucose, blood lipids and C-reactive protein (CRP) in healthy subjects. A total of 5 males and 5 females (aged 31.8±6.6 years, weighing 66.2±12.9 kg) were randomly assigned into one of two groups and either consumed 500 ml PJ/day or no PJ for 14 days. Blood samples were obtained from participants prior to and following the experimental period. PJ consumption resulted in a significant increase in red blood cell count (P<0.05), hemoglobin levels (P<0.001) and hematocrit levels (P<0.05). Other CBC parameters, glucose, cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein and CRP levels did not significantly change following PJ consumption. These results indicate that PJ intake for a short period of time may result in increased erythropoiesis or decreased degradation without any significant alterations in factors associated with metabolic health and inflammation in healthy individuals.

Effects of Pomegranate Juice on Cardiovascular Risk Factors in Patients with Metabolic Syndrome: a Double-Blinded, Randomized Crossover Controlled Trial.

The aim of this study is to investigate the simultaneous effect of pomegranate juice on components of the metabolic syndrome, including high sensitive C-reactive protein (hs-CRP) as an inflammatory index and glycemic and lipid profile indices in patients with metabolic syndrome. In a double- blind 2*2 crossover study, 30 individuals suffering from metabolic syndrome received a daily dose of 500 mL pomegranate juice for a period of one week. After one week of wash out period, they received a placebo for one week. Lipid profile, blood glucose control indices including fasting blood glucose, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), systolic and diastolic blood pressure, and hs-CRP were measured at the beginning and end of the study. To analyze the data, a repeated measure analysis of variance and a t-test were performed. The results indicated that in comparison to the placebo, pomegranate juice was more effective in reducing the systolic and diastolic blood pressure (p=0.00) and hs-CRP (p=0.018). The level of triglyceride (p=0.030) and very low-density lipoproteins cholesterol (VLDL-C) (p=0.014) were increased after the consumption of pomegranate juice, as opposed to the baseline condition. The rest of lipid profile, fasting blood glucose (FBS), insulin, and HOMA-IR of the participants did not show any significant difference. Natural pomegranate juice supplementation lowered the level of systolic and diastolic blood pressure in patients with metabolic syndrome as well as their blood hs-CRP. However, it also increased their triglyceride and VLDL-C.

Daily supplementation with fresh pomegranate juice increases paraoxonase 1 expression and activity in mice fed a high-fat diet.

Studies have found that pomegranate juice (PJ) consumption increases the binding of high-density lipoproteins (HDL) to paraoxonase 1 (PON1), thus increasing the catalytic activity of this enzyme. PON1 is an antioxidant arylesterase synthesized in the liver and transported in plasma in association with HDL. Decreased levels of PON1 are associated with higher levels of cholesterol. We determined the effects of PJ on body weight, cholesterol, and triacylglycerols through 5 months of supplementation. In addition, the effect of PJ on pon1 gene expression in the liver was also measured by RT-qPCR as well as the activity in serum by a semiautomated method using paraoxon as a substrate. CD-1 mice were either fed a control diet or were fed a high-fat diet 1.25% (wt/wt) cholesterol, 0.5% (wt/wt) sodium cholate, and 15% (wt/wt) saturated fat. 300 μL of PJ containing 0.35mmol total polyphenols was administered by oral gavage to half of the high fat mice daily. The rest of the high fat mice and the control mice were administered with 300 μL of water. PJ-supplemented animals had significantly higher levels of expression of pon1 compared to the unsupplemented group. PJ-supplemented animals had twice the PON1 activity of the unsupplemented group. In addition, PJ-supplemented animals had the lowest body weight and significantly reduced cholesterol and triacylglycerol levels, although the tricylglycerol levels were not consistently decreased. These results suggest that PJ protects against the effects of a high-fat diet in body weight, and cholesterol levels.

Effects of pomegranate juice on blood pressure: A systematic review and meta-analysis of randomized controlled trials

Punica granatum L. (Pomegranate) has been claimed to provide several health benefits. Pomegranate juice is a polyphenol-rich fruit juice with high antioxidant capacity. Several studies suggested that pomegranate juice can exert antiatherogenic, antioxidant, antihypertensive, and anti-inflammatory effects. Nevertheless, the potential cardioprotective benefits of pomegranate juice deserve further clinical investigation. To systematically review and meta-analyze available evidence from randomized placebo-controlled trials (RCTs) investigating the effects of pomegranate juice consumption and blood pressure (BP). A comprehensive literature search in Medline and Scopus was carried out to identify eligible RCTs. A meta-analysis of eligible studies was performed using a random-effects model. Quality assessment, sensitivity analysisand publication bias evaluations were conducted using standard methods. Quantitative data synthesis from 8 RCTs showed significant reductions in both systolic [weighed mean difference (WMD): −4.96mmHg, 95% CI: −7.67 to −2.25, p<0.001) and diastolic BP (WMD: −2.01mmHg, 95% CI: −3.71 to −0.31, p=0.021) after pomegranate juice consumption. Effects on SBP remained stable to sensitivity analyses. Pomegranate juice reduced SBP regardless of the duration (>12 wks: WMD=−4.36mmHg, 95% CI: −7.89 to −0.82, p=0.016) and <12 wks: WMD=−5.83 mmHg, 95% CI: −10.05 to −1.61, p=0.007) and dose consumed (>240cc: WMD=−3.62mmHg, 95% CI: −6.62 to −0.63, p=0.018) and <240cc: WMD=−11.01mmHg, 95% CI: −17.38 to −4.65, p=0.001, pomegranate juice per day) whereas doses >240cc provided a borderline significant effect in reducing DBP. The present meta-analysis suggests consistent benefits of pomegranate juice consumption on BP. This evidence suggests it may be prudent to include this fruit juice in a heart-healthy diet.

Pomegranate juice prevents development of non-alcoholic fatty liver disease in rats by attenuating oxidative stress and inflammation.

The effects of pomegranate juice (PJ) on the risk factors of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) have been reported previously; however, the effects on NAFLD and its prevention have not yet been clarified. The present study aimed to evaluate the effects of PJ consumption with respect to the prevention of NAFLD/NASH development. Sprague-Dawley rats were fed either a high-fat, high sugar diet (model group); a high-fat, high sugar diet plus PJ (model+PJ); or a chow diet ad libitum for 7 weeks. Serum levels of fasting glucose, triglyceride, cholesterol, liver enzymes, insulin and hepatic tumor necrosis factor-α and tissue growth factor-β gene expression were determined. Hepatic histology was examined by hemotoxylin and eosin staining. The model+PJ group had significantly lower hepatic steatosis, ballooning, lobular inflammation and portal inflammation (P < 0.001); lower hepatic pro-inflammatory and pro-fibrotic gene expression (P < 0.001); and lower plasma levels of alanine aminotransferase (P = 0.026), aspartate aminotransferase (P = 0.041), insulin (P < 0.001), triglycerides (P = 0.041) and glucose (P = 0.009) compared to the model group; however, weight gain, food intake and plasma high-density lipoprotein levels were not significantly different between these two groups. The data obtained in the present study indicate that the regular consumption of PJ can prevent NAFLD even in the presence of the other risk factors such as obesity, hypercholesterolemia, and high energy, fat and sugar intakes. © 2016 Society of Chemical Industry.

Effects of pomegranate juice consumption on oxidative stress in patients with type 2 diabetes: a single-blind, randomized clinical trial

Increased free radicals production due to hyperglycemia produces oxidative stress in patients with diabetes. Pomegranate juice (PJ) has antioxidant properties. This study was conducted to determine the effects of PJ consumption in oxidative stress in type 2 diabetic patients.This study was a randomized clinical trial performed on 60, 40–65 years old diabetic patients.The patients were randomly allocated either to PJ consumption group or control. Patients in PJ group consumed 200 ml of PJ daily for six weeks. Sex distribution and the mean age were not different between two groups. After six weeks intervention, oxidized LDL and anti-oxidized LDL antibodies decreased and total serum antioxidant capacity and arylesterase activity of paraoxonase increased significantly in the PJ-treated group compared to the control group. Our data have shown that six weeks supplementation of PJ could have favorable effects on oxidative stress in patients with type 2 diabetes (T2D).

Effects of Grapefruit and Pomegranate Juices on the Pharmacokinetic Properties of Dapoxetine and Midazolam in Healthy Subjects.

The package leaflet for dapoxetine, an effective treatment for premature ejaculation, includes a strict warning against coadministration with drugs or herbal remedies that strongly induce or inhibit the activity of Cytochrome P450 (CYP) 3A4 enzyme. To assess the effects of multiple daily consumption of grapefruit juice (GFJ) and pomegranate juice (PJ) on the pharmacokinetics of dapoxetine, we conducted an open-label, three-way crossover study in 12 healthy subjects using midazolam as a probe substrate for CYP3A4. Participants received a single oral dose of dapoxetine (60mg) and midazolam (7.5mg) after pretreatment with 250ml of either water, undiluted GFJ, or PJ for three consecutive days. All subjects were monitored for adverse effects during the study period. Compared to pretreatment with water, GFJ increased the area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) and peak plasma concentration (C max) of dapoxetine by 60 and 80%, respectively, and prolonged its elimination half-life (t 1/2) by 43%. Similar effects of GFJ on the pharmacokinetics of midazolam were observed with a significant increase in AUC0-∞ (75%), C max (40%), and t 1/2 (92%). Slight but not statistically significant changes were observed in the pharmacokinetics of dapoxetine and midazolam after pretreatment with PJ. Time to reach C max (T max) did not differ among the three phases. These results suggest that GFJ increases the extent of absorption and reduces clearance of dapoxetine possibly by inhibition of both intestinal and hepatic CYP3A4, whereas PJ has little effect on dapoxetine pharmacokinetics. Although the impact of GFJ on the pharmacokinetics of dapoxetine was mild, a great caution should be considered when they are concomitantly administered.

The effect of pomegranate juice on clinical signs, matrix metalloproteinases and antioxidant status in patients with knee osteoarthritis.

Osteoarthritis (OA) is one of the commonest forms of musculoskeletal disorders that leads to joint degeneration and has a major impact on patients' quality of life. Experimental and in vitro studies have suggested the protective roles of pomegranate juice (PJ) as a rich antioxidant source for mitigating cartilage inflammation. In this interventional study, 38 patients with knee OA were randomly divided into two groups: PJ or control for 6 weeks to evaluate the effect of this intervention on clinical signs, inflammation and antioxidant status. Significant decreases in Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) total score (P = 0.01), stiffness score (P = 0.00) and physical function score (P = 0.01) were observed in PJ group after the intervention. The means of serum levels of matrix metalloproteinase (MMP)-13 was significantly decreased (P = 0.02) and glutathione peroxidase was increased in the intervention group compared with the control group after the study period (P = 0.02). According to the findings of this clinical trial, PJ consumption can improve physical function and stiffness, decrease breakdown cartilage enzymes and increase antioxidant status in patients with knee OA. © 2016 Society of Chemical Industry.

Comparison of Different Extraction Methods in the Analysis of Volatile Compounds in Pomegranate Juice

Consumption and production of pomegranate fruit and juice have been increasing. Many pomegranate volatile reports involved commercial samples, complicated isolation methods, or different cultivars. In this study, three different techniques including simultaneous distillation extraction (SDE), headspace solid-phase micro-extraction (HS-SPME), and purge and trap (P&T) with Tenax TA absorbent were employed to extract the aromatic compounds of two different juices (PJ and PJS) of red Socotran pomegranate. A total of 36 compounds were identified by gas chromatography-mass spectrometry (GC-MS). The results showed that the P&T and HS-SPME methods complementarily contributed to extract the aroma compounds related with the pomegranate flavor, and the most important contributors to the pomegranate juice flavors were identified as n-hexaldehyde, leaf aldehyde, 1-hexyl alcohol, butyl acetate, myrcene, and phenyl acetaldehyde in this paper.

Effects of Pomegranate Juice on Hormonal Biomarkers of Breast Cancer Risk

Pomegranate is a rich source of polyphenols. Laboratory studies suggest polyphenols may exert breast cancer preventive effects through modulation of endogenous sex hormone levels. The aim of this study was to determine the effect of pomegranate juice consumption on serum levels of estradiol, estrone, testosterone, androstenedione, and sex hormone binding globulin (SHBG). Sixty-four healthy postmenopausal women were randomly assigned to drink 8 ounces of either 100% commercial pomegranate juice (intervention) or apple juice (control) for 3 weeks. Overall, women in the intervention group did not experience any significant decline in serum sex hormones or SHBG compared to women in the control group. In subgroup analyses restricted to 38 normal weight women, women in the intervention group compared to control group had a significant decline in estrone (pg/mL) and testosterone levels (pg/mL): pomegranate: −61.6 [95% confidence interval (CI): −175.8 to 52.6), apple: 1.1 (95% CI: −5.4 to 7.7), P = 0.05, and pomegranate: −289.1 (95% CI: −630.7 to 52.5), apple: 79.6 (95% CI: −77.8 to 236.9), P = 0.03, respectively. Because of several study limitations, results should be considered preliminary. Additional larger trials would be needed to determine effects in normal versus overweight/obese women.

Soy protein isolate does not affect ellagitannin bioavailability and urolithin formation when mixed with pomegranate juice in humans

We investigated the effect of mixing soy protein isolate and pomegranate juice (PJ) on the bioavailability and metabolism of ellagitannins (ETs) in healthy volunteers. Eighteen healthy volunteers consumed PJ alone or PJ premixed with soy protein isolate (PJSP). The concentration of plasma ellagic acid (EA) and urine urolithins was measured. There was no significant difference in plasma EA over a 6-h period between the two interventions. While the maximum concentration of plasma EA after PJSP consumption was slightly but significantly lower than after PJ consumption, EA remained in the plasma longer with an elimination half-life t1/2E at 1.36±0.59 versus 1.06±0.47h for PJSP and PJ consumption, respectively. Urinary urolithin A, B and C was not significantly different between the two interventions. In conclusion, premixing soy protein isolate and PJ did not affect the bioavailability or the metabolism of pomegranate ETs in healthy volunteers.

Pomegranate juice polyphenols induce a phenotypic switch in macrophage polarization favoring a M2 anti-inflammatory state.

It was documented that pomegranate has anti-inflammatory effects. In this study, we investigated a direct effect of pomegranate juice (PJ) and its polyphenols on macrophage inflammatory phenotype. In vitro, PJ and its major polyphenols dose-dependently attenuated macrophage response to M1 proinflammatory activation in J774.A1 macrophage-like cell line. This was evidenced by a significant decrease in TNFα and IL-6 secretion in response to stimulation by IFNγ and Lipopolysaccharide. In addition, PJ and punicalagin dose-dependently promoted the macrophages toward a M2 anti-inflammatory phenotype, as determined by a significant increase in the spontaneous secretion of IL-10. In mice, supplementation with dietary PJ substantially inhibited the M2 to M1 macrophage phenotypic shift associated with age, toward a favorable anti-inflammatory M2 phenotype. This effect was also reflected in the mice atherosclerotic plaques, as evaluated by the distinct expression of arginase isoforms. PJ consumption inhibited the increment of arginase II (Arg II, M1) mRNA expression during aging, and maintained the levels of Arg I (M2) expression similar to those in young mice aorta. This study demonstrates, for the first time, that pomegranate polyphenols directly suppress macrophage inflammatory responses and promote M1 to M2 switch in macrophage phenotype. Furthermore, this study indicates that PJ consumption may inhibit the progressive proinflammatory state in the aorta along atherosclerosis development with aging, due to a switch in macrophage phenotype from proinflammatory M1 to anti-inflammatory M2.

Pomegranate (Punicagranatum) juice decreases lipid peroxidation, but has no effect on plasma advanced glycated end-products in adults with type 2 diabetes: a randomized double-blind clinical trial

IntroductionDiabetes mellitus characterized by hyperglycemia could increase oxidative stress and formation of advanced glycated end-products (AGEs), which contribute to diabetic complications. The purpose of this study was to assess the effect of pomegranate juice (PJ) containing natural antioxidant on lipid peroxidation and plasma AGEs in patients with type 2 diabetes (T2D).Materials and methodsIn a randomized, double-blind, placebo-controlled trial, 44 patients (age range 56±6.8 years), T2D were randomly assigned to one of two groups: group A (PJ, n=22) and group B (Placebo, n=22). At the baseline and the end of 12-week intervention, biochemical markers including fasting plasma glucose, insulin, oxidative stress, and AGE markers including carboxy methyl lysine (CML) and pentosidine were assayed.ResultsAt baseline, there were no significant differences in plasma total antioxidant capacity (TAC) levels between the two groups, but malondialdehyde (MDA) decreased levels were significantly different (P<0.001). After 12 weeks of intervention, TAC increased (P<0.05) and MDA decreased (P<0.01) in the PJ group when compared with the placebo group. However, no significant differences were observed in plasma concentration of CML and pentosidine between the two groups.ConclusionsThe study showed that PJ decreases lipid peroxidation. Therefore, PJ consumption may delay onset of T2D complications related to oxidative stress.

Abstract 4108: Efficacy of ellagic acid and its major urolithin metabolites in inhibiting growth of prostate cancer cells

Abstract Pomegranate juice, in the last several years, has gained tremendous attention for its proven ability to slow down prostate cancer as evident by reduced prostate-specific antigen doubling time. However, a bioactive compound responsible for this action has not yet been confirmed and thus, limited its chemo-preventive/therapeutic potential. Pharmacokinetic studies of oral consumption of pomegranate juice in human have shown partial hydrolysis of ellagitannins, major component in the juice, into ellagic acid which is subsequently converted to various urolithin metabolites by the gut microbial digestion. Urolithins are shown to have extended plasma half-life and are detected in urine up to 48 after oral consumption of pomegranate juice. We investigated the potential of ellagic acid and major urolithin metabolites; urolithin A and urolithin B, that were synthesized in our laboratory, in inhibiting the growth and survival of androgen-independent prostate cancer cells, PC-3 and DU-145 cells in vitro. We found significantly high dose and time-dependent inhibition of growth and proliferation of both cell lines by all three compounds tested. Ellagic acid was found to be the most potent inhibitor as evident by significantly lower IC50 of 8.17 µM and 1.57µM respectively for DU-145 and PC-3 cells after 48 hours. Urolithin B was more efficient than Urolithin A against DU-145 cells (IC50 of 17.42µM vs. 73.78µM) while it was reversed in PC-3 cells (IC50 of 92.25 µM vs. 36.96 µM). Similarly, these compounds also induced substantial levels of dose-dependent apoptosis in either cell lines, however, with variable sensitivity. Western blot analysis of signaling proteins to elucidate the molecular mechanisms of observed effects correlated with altered levels of proteins that mediate cell-cycle regulation. P21, an inhibitor of CDK2-CyclinA/E complex that regulates protein elongation and cell-cycle progression from G1 to S phase was highly upregulated in compound-treated PC-3 cells and DU-145 cells, while cyclinD1 which regulates G1 to S phase transition in consort with CDK4 was significantly decreased in treated cells in comparison to untreated and vehicle-treated control. Studies are underway to understand the synergistic effects between these compounds, in vitro and in vivo. Taken together, our results indicates EA and its gut metabolites are significant anti-survival and anti-proliferation candidates against prostate cancer cells and hold a tremendous chemo-therapeutic and chemo-preventive potential, for its high efficacy and natural, low toxic source. Citation Format: Anil Poudel, Manicka V. Vadhanam, Joseph Burlison. Efficacy of ellagic acid and its major urolithin metabolites in inhibiting growth of prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4108. doi:10.1158/1538-7445.AM2014-4108

Fresh pomegranate juice ameliorates insulin resistance, enhances β-cell function, and decreases fasting serum glucose in type 2 diabetic patients

Although the effects of pomegranate juice (PJ) on type 2 diabetic (T2D) conditions have been reported, a clinical study focusing on the short-term effects on different diabetic variables is still needed. We hypothesized that PJ consumption by T2D patients could reduce their insulin-resistant state and decrease their fasting serum glucose (FSG) levels, 3 hours after juice ingestion. This study demonstrated the direct effect of fresh PJ on FSG and insulin levels in T2D patients. Blood samples from 85 participants with type 2 diabetes were collected after a 12-hour fast, then 1 and 3 hours after administration of 1.5 mL of PJ, per kg body weight. Serum glucose was measured based on standard methods using the BS-200 Chemistry Analyzer (Shenzhen Mindray Bio-Medical Electronics Co Ltd, Shenzhen, China). Commercially available immunoassay kits were used to measure human insulin. Generally, the results demonstrated decreased FSG, increased β-cell function, and decreased insulin resistance among T2D participants, 3 hours after PJ administration (P < .05). This hypoglycemic response depended on initial FSG levels, as participants with lower FSG levels (7.1-8.7 mmol/L) demonstrated a greater hypoglycemic response (P < .05) compared with those who had higher FSG levels (8.8-15.8 mmol/L). The effect of PJ was also not affected by the sex of the patient and was less potent in elderly patients. In conclusion, this work offers some encouragement for T2D patients regarding PJ consumption as an additional contribution to control glucose levels.

Pomegranate juice consumption increases GSH levels and reduces lipid and protein oxidation in human blood

The aim of the present study was the assessment of the antioxidant effects of pomegranate juice (PJ) consumption in humans. Thus, 14 healthy volunteers consumed PJ daily for a period of 15days and the changes of oxidative stress markers in their blood were assessed at four different time points, immediately before the experiment (T1), after 15days of juice administration (T2), one (T3) and three weeks (T4) after the interruption of PJ administration. The markers studied were total antioxidant capacity (TAC), levels of malondialdehyde (MDA), and protein carbonyls (CARB) measured in plasma, as well as reduced glutathione (GSH), and catalase activity (CAT) measured in erythrocytes. The MDA was reduced by 24.4% at T3 and CARB were reduced by 19.6% and 17.7% at T2 and T3, respectively, supporting the evidence that PJ consumption enhances the antioxidant status in humans by decreasing lipid peroxidation and protein oxidation. Moreover, GSH levels were significantly increased (22.6%) at T2, indicating that PJ consumption improves the antioxidant mechanisms in erythrocytes by increasing GSH levels. Finally, it was shown that even a week after stopping PJ consumption some of its beneficial effects on antioxidant status still remained in the organism.