Effects Of Pomegranate Fruit Extract Research Articles

Pomegranate (P. granatum) fruit juice protects against iron-induced oxidative testicular injury via amelioration of oxidative imbalance and modulation of metabolic indices linked to male infertility

Male infertility is a challenging clinical condition that threatens global reproductive health. Majority of the issues found in testicular dysfunction are associated with oxidative stress. The present study investigated the protective effect of pomegranate fruit extract against Fe2+- mediated oxidative testicular injury using ex vivo experimental models. Testicular oxidative injury was induced by incubating testes tissues in Krebs buffer and FeSO4.7H20 solution, and treated by co-incubating with different concentrations (30–240 μg/mL) of pomegranate fruit extract for 90 min (37 °C), with gallic acid serving as the standard antioxidant. Oxidative injury induction led to significant (p < 0.05) elevation of testicular malondialdehyde and LDL-cholesterol concentration, acetylcholinesterase, ATPase, fructose-1,6-bisphosphatase, glycogen phosphorylase and lipase activities. These were concomitantly accompanied by depleted levels of reduced glutathione, glycogen, total cholesterol, triglyceride and HDL-cholesterol and activities of superoxide dismutase, catalase, ENTPDase and 5′Nucleotidase. It also led to distorted testicular histological architecture. Treatment with the fruit extract markedly reversed these levels and activities and preserved testicular morphology. Octadecenoic acid, 1,2,3-propanetriyl ester, (E,E,E)-; squalene and cholesterol, while concomitantly generating 6-Octadecenoic acid, (Z)-; (2Z)-2-Octenoic acid; methyl tetradecanoate; methyl 14-methylpentadecanoate; octadecanoic acid, 2-[(1-oxohexadecyl)oxy]ethyl ester and cholestan-3-ol, 2-methylene-, (3.beta.,5.alpha.)-. This was accompanied by the deactivation of alpha linolenic acid and linoleic acid metabolism, and steroidogenesis. Treatment with pomegranate depleted the oxidative-generated metabolites, while concomitantly generating arachidonic acid, cholesterol margranate and ethyl lithocholate, and reactivating the inactivated pathways. The results indicate the protective effect of pomegranate fruit juice against oxidative testicular injury.

A standardized pomegranate fruit extract ameliorates thioacetamide-induced liver fibrosis in rats via AGE-RAGE-ROS signaling

This work aimed to investigate a possible mechanism that may mediate the hepatoprotective effects of pomegranate fruit extract (PFE) against thioacetamide (THIO)-induced liver fibrosis in rats. Male Sprague Dawley rats were randomly allocated into four groups (n = 8 each): control; PFE (150 mg/kg/day, orally); THIO (200 mg/kg, i.p, 3 times a week); and THIO and PFE-treated groups. Oral PFE treatment decreased liver/body weight ratio by 12.4%, diminished serum function levels of ALT, AST, ALP, LDH, and total bilirubin, increased serum albumin, boosted hepatic GSH (by 35.6%) and SOD (by 17.5%), and significantly reduced hepatic levels of ROS, MDA, 4-HNE, AGEs, and RAGE in THIO-fibrotic rats relative to untreated THIO group. Moreover, PFE administration downregulated the hepatic levels of profibrotic TGF-β1 (by 23.0%, P < 0.001) and TIMP-1 (by 41.5%, P < 0.001), attenuated α-SMA protein expression, decreased serum HA levels (by 41.3%), and reduced the hepatic levels of the fibrosis markers hydroxyproline (by 26.0%, P < 0.001), collagen type IV (by 44.3%, P < 0.001) and laminin (by 43.4%, P < 0.001) compared to the untreated THIO group. The histopathological examination has corroborated these findings, where PFE decreased hepatic nodule incidence, attenuated portal necroinflammation and reduced extent of fibrosis. These findings may suggest that oral PFE administration could slow the progression of hepatic fibrogenesis via reducing hepatic levels of AGEs, RAGE, ROS, TGF-β1, and TIMP-1.

Modulatory effect of pomegranate extract on TRPA1, TRPM2 and caspase-3 expressions in colorectal cancer induction of mice

Abstract Objectives This study aimed to evaluate the effects of pomegranate fruit extract (PFE) on levels of transient receptor potential (TRP) channel and caspase-3 (Casp-3) expressions, tumor necrosis factor-α (TNF-α), total sialic acid (TSA), reduced glutathione (GSH), and malondialdehyde (MDA) in mice with induced colorectal cancer (CRC) by investigating effects of PFE on in vitro mitotic index (MI). Methods Different PFE concentrations on​​ MI against 0.3 μg/mL mitomycin-C (MMC) in cell culture were evaluated by binocular light microscopy. During in vivo applications on Balb/c mice, it was given once physiological saline to group I, PFE for ten weeks to group II, a single dose of azoxymethane (AOM) plus dextran sulfate sodium in drinking water (DSS) to group III, and AOM plus DSS plus PFE to group IV. Tissue samples were evaluated by western blotting, spectrophotometric, and histopathological methods. Results Expressions of Casp-3, TRP ankyrin 1 (TRPA1), and melastatin 2 (TRPM2) channels and TNF-α, TSA, GSH, and MDA concentrations in evaluated tissues had significantly better levels in PFE-treated groups compared to CRC-induced mice. Conclusions Results of the present study indicate that PFE application in mice with induced CRC may be an important modulator of TRPA1 and TRPM2 channels, apoptosis, and inflammatory response by decreasing oxidative stress.

Pomegranate (Punica granatum) Fruit Extract Suppresses Cancer Progression and Tumor Angiogenesis of Pancreatic and Colon Cancer in Chick Chorioallantoic Membrane Model

Pomegranate fruit extract contains many polyphenols and flavonoids of diverse biological importance including anticancer potential. In cancer, the angiogenesis process facilitates solid cancer growth and metastasis. Here, the antiangiogenic effect of pomegranate fruit extract against human pancreatic cancer (Suit-2) and colon (colo205) cell lines in the chick chorioallantoic membrane (CAM) model was studied along with the effect of pomegranate fruit extract on fibroblast growth factor (FGF2). Pomegranate fruit extract significantly reduced the tumor weight and hemoglobin content in CAM models of pancreatic Suit-2 and colon colo205.

Chondrogenic activity of two herbal products; pomegranate fruit extract and avocado/soybean unsaponifiable.

Background and purpose:Articular cartilage defects aren’t repaired by itself. Numerous studies have been conducted in the area of cartilage tissue engineering and some of them considered herbal products. An attempt was made in this study to compare the effects of pomegranate fruit extract (PFE), avocado/soybean unsaponifiable (ASU), and their equal proportional mixture on the chondrogenesis of human adipose-derived stem cells (hADSCs).Experimental approach:PFE was prepared through the percolation method. ASU powder was dissolved in ethanol at 10 μg/mL concentration and was sterilized. The hADSCs first were isolated, expanded in monolayer culture and identified, and next seeded on fibrin scaffolds. The hADSCs/fibrin scaffolds were divided into 4 groups of control, ASU, PFE, and PFE+ ASU and subjected to in vitro induction for 2 weeks. The control group received chondrogenic medium, other groups received chondrogenic medium plus ASU, PFE, or PFE + ASU, respectively. The MTT assay was performed for cell viability evaluation, real-time polymerase chain reaction for expression of cartilage genes, and the toluidine blue, safranin-O, and immunohistochemistry for staining of the constructs.Findings / Results:Cell viability, cartilage genes expression, matrix staining density, and collagen II protein levels in PFE samples were significantly higher than those of the other groups (P < 0.05). Histological assessments revealed more chondrogenic centers (P < 0.05) in the PFE group compared to the other groups.Conclusion and implications:In this study, it was revealed that PFE can be considered as an induction factor for future chondrogenic studies.

Effectiveness of Pomegranate (Punica granatum L.) Fruit Extract on the Sexual Function in Rats

Background: Pomegranate (Punica granatum L.) has been mentioned to be of value in the management of male sexual disorders. This study investigated the effects of pomegranate fruit extract on healthy male rats as the animal model. Materials and methods: 50 adult male and female Albino rats of Wistar strain weighing 250-350 g and 200-250 g respectively were used in this study. The pomegranate extract was administered (500, 1000 and 1500 mg/kg) to different groups of male rats on a once-daily regime throughout the experiment period. The general mating behaviour, libido, potency and testosterone concentration were studied and compared with sildenafil citrate. Results: Administration of the pomegranate extract orally at the dose of 1500 mg/kg produced significant augment of sexual activity in male rats. The mounting frequency, intromission frequency, mounting latency, intromission latency, ejaculation latency and post ejaculation interval did not vary significantly. However, the mounting frequency varied significantly between control, pomegranate crude extracts and sildenafil. In addition, the potency of the extracts did not vary significantly between control, pomegranate crude extracts and sildenafil. The testosterone levels varied significantly between pomegranate, sildenafil and control. Conclusion: Pomegranate extracts have the potential of increasing sexual behaviour in rats. There is need for mass production of pomegranate extracts for use in enhancing sexual behaviour

Inhibition of cartilage degradation and suppression of PGE2 and MMPs expression by pomegranate fruit extract in a model of posttraumatic osteoarthritis

ObjectiveOsteoarthritis (OA) is characterized by cartilage degradation in the affected joints. Pomegranate fruit extract (PFE) inhibits cartilage degradation in vitro. The aim of this study was to determine whether oral consumption of PFE inhibits disease progression in rabbits with surgically induced OA. MethodsOA was surgically induced in the tibiofemoral joints of adult New Zealand White rabbits. In one group, animals were fed PFE in water for 8 wk postsurgery. In the second group, animals were fed PFE for 2 wk before surgery and for 8 wk postsurgery. Histologic assessment and scoring of the cartilage was per Osteoarthritis Research Society International guidelines. Gene expression and matrix metalloproteinases (MMP) activity were determined using quantitative reverse transcriptase polymerase chain reaction and fluorometric assay, respectively. Interleukin (IL)-1 β, MMP-13, IL-6, prostaglandin (PG)E2, and type II collagen (COL2A1) levels in synovial fluid/plasma/culture media were quantified using enzyme-linked immunosorbent assay. Expression of active caspase-3 and poly (ADP-ribose) polymerase p85 was determined by immunohistochemistry. Effect of PFE and inhibitors of MMP-13, mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB was studied in IL-1 β-stimulated rabbit articular chondrocytes. ResultsSafranin-O-staining and chondrocyte cluster formation was significantly reduced in the anterior cruciate ligament transaction plus PFE fed groups. Expression of MMP-3, MMP-9, and MMP-13 mRNA was higher in the cartilage of rabbits given water alone but was significantly lower in the animals fed PFE. PFE-fed rabbits had lower IL-6, MMP-13, and PGE2 levels in the synovial fluid and plasma, respectively, and showed higher expression of aggrecan and COL2A1 mRNA. Significantly higher numbers of chondrocytes were positive for markers of apoptosis in the joints of rabbits with OA given water only compared with those in the PFE-fed groups. PFE pretreatment significantly reduced IL-1 β induced IL-6 and MMPs expression in rabbit articular chondrocytes. These effects were also mimicked using MMP-13, MAPK, and NF-κB inhibitors in IL-1 β-stimulated rabbit chondrocytes. In an in vitro activity assay, PFE blocked the activity of MMP-13. Like MAPK and NF-κB inhibitors, PFE was also effective in inhibiting IL-1 β-induced PGE2 production in rabbit chondrocytes. PFE also reversed the inhibitory effect of IL-1β on COL2A1 mRNA and protein expression in IL-1 β-stimulated rabbit chondrocytes. ConclusionThe present data highlight the chondroprotective effects of PFE oral consumption in a model of posttraumatic OA and suggest that PFE-derived compounds may have potential value in the management of OA.

Intake of Pomegranate Prevents the Onset of Osteoarthritis : Molecular Evidences

Intake of Pomegranate Prevents the Onset of Osteoarthritis : Molecular Evidences

Anti-Glycation Effects of Pomegranate (Punica granatum L.) Fruit Extract and Its Components in Vivo and in Vitro.

Accumulation of advanced glycation end products (AGEs) leads to various diseases such as diabetic complications and arteriosclerosis. In this study, we examined the effect of pomegranate fruit extract (PFE) and its constituent polyphenols on AGE formation in vivo and in vitro. PFE, fed with a high-fat and high-sucrose (HFS) diet to KK-A(y) mice, significantly reduced glycation products such as glycoalbumin (22.0 ± 2.4%), hemoglobin A1c (5.84 ± 0.23%), and serum AGEs (8.22 ± 0.17 μg/mL), as compared to a control HFS group (30.6 ± 2.6%, 7.45 ± 0.12%, and 9.55 ± 0.17 μg/mL, respectively, P < 0.05). In antiglycation assays, PFE, punicalin, punicalagin, ellagic acid, and gallic acid suppressed the formation of AGEs from bovine serum albumin and sugars. In this study, we discuss the mechanism of the antiglycation effects of PFE and its components in vivo and in vitro.

The effect of pomegranate fruit extract on testosterone‐induced BPH in rats

Benign prostatic hyperplasia (BPH) affects many men after the age of 50 years. Inflammation and oxidative stress along with apoptotic changes are thought to play an important role in the pathology of BPH. Pomegranate contains a variety of polyphenolic compounds that have been studied in a medley of diseases for their anti-oxidant, anti-inflammatory and pro-apoptotic properties. Therefore, this study examined the effect of Pomegranate Fruit Extract (PFE) on the development of BPH using a testosterone-induced BPH model in rats. A total of 48 rats were randomly divided into six groups of eight, one group served as the control, BPH was induced by testosterone 3 mg/kg S.C. daily in four groups, three of them received PFE by oral gavage daily at doses of 25, 50, and 100 mg/kg respectively, while one group received PFE at a dose of 50 mg/kg without induction of BPH. PFE at a dose of 100 mg/kg was the most effective in decreasing testosterone-induced increase in prostate weight, prostate weight/body weight ratio, and PAP levels by 30.8%, 55%, and 68% respectively and in preventing the accompanying histological changes. In the BPH model, testosterone significantly decreased GSH, SOD, and CAT to 0.45, 0.64, and 0.88 of the control group values respectively, and significantly increased MDA by >6-fold. In combination with testosterone, PFE dosed at 100 mg/kg significantly increased GSH, SOD, and CAT to 0.83, 0.92, and 0.93 of the control group values respectively, whereas MDA was significantly decreased by 72% compared with the testosterone treated group. In addition to this, at the range of doses studied, PFE lowered COX-II, iNOS, Ki-67 expression, and increased apoptotic index. The current findings elucidate the effectiveness of PFE in preventing testosterone-induced BPH in rats. This could be attributed, at least partly, to its anti-oxidant, anti-inflammatory, and pro-apoptotic properties.

The Pharmacological, Physiological and Toxicological Effects of Pomegranate Fruit Extract and its Constituents

The Pharmacological, Physiological and Toxicological Effects of Pomegranate Fruit Extract and its Constituents

The Antidepressant-Like Effects of &amp;lt;i&amp;gt;Punica granatum&amp;lt;/i&amp;gt; (Pomegranate) Extract in Mice

The aim of the present work is to evaluate the putative antidepressant-like effects of pomegranate fruit extract including seeds (PFE) on the performance of male mice in the forced swimming test (FST), after acute administration, after short-term treatment (7 days) and, after repeated administration in a 24-h period (24, 12 and 1 h before swimming test). A single dose (20 ml/kg p.o.) of PFE, in male mice provoked a significant reduction of the immobility time. Such effect was also observed with short-term treatment (7 days) with doses of 1 and 10 ml/kg/day of PFE. Moreover, it was noted that there were important differences in the onset of the antidepressant-like effect in the FST, depending on the modality of treatment with PFE. Both efficacy and potency were higher when repeated administration of PFE was used, and surprisingly the dose of 10 ml/kg (24, 12 and 1 h before swimming test) was as effective as Fluoxetine. In the same way, the short term administration (7 days) improved significantly efficacy and potency of the PFE in comparison to a single dose treatment. These results indicate an antidepressant-like profile of action for PFE which deserves further research.

Protective effects of pomegranate on electrocardiographic, biochemical and histoarchitectural changes in isoproterenol induced myocardial infarction in rats

Aims: This study is aimed to investigate the protective effects of Pomegranate fruit extract on ECG, biochemical and histoarchitectural changes in isoproterenol (ISO) induced myocardial infarction in rats.Materials and Methods: Male albino rats were treated with Pomegranate fruit extracts (100 mg/kg/day, p.o) for a period of 30 days. ISO (200 mg/kg, s.c) was injected to rats on 29th and 30th day at an interval of 24 h to produce myocardial infarction. On day 31st electrocardiographic, biochemical, histoarchitectural and apoptotic changes were monitored from control and experimental groups.Results: ISO injected rats showed a significant alteration in ECG pattern. The levels of cardiac and inflammatory markers such as Lactate dehydrogenase and creatine phosphokinase-MB were significantly increased. A significant alteration in lipid peroxidation and biomarkers of oxidative stress (GSH, SOD and CAT) were observed. In addition, it also showed significant alteration in collagen content (Masson's Trichrome staining) and glycogen content (Periodic acid Schiff's staining) of the heart. Treatment with Pomegranate fruit extract (PGFE) significantly reduced ISO induced alteration in ECG, biochemical and histoarchitectural changes.Conclusions: In conclusion the present study showed that treatment of PGFE significantly attenuates myocardial infarction induced by isoproterenol.

Pomegranate Fruit Extract Inhibits UVB‐induced Inflammation and Proliferation by Modulating NF‐κB and MAPK Signaling Pathways in Mouse Skin†

There is considerable interest in the identification of natural agents capable of affording protection to skin from the adverse effects of solar ultraviolet B (UVB) radiation. Pomegranate (Punica granatum L.) fruit possesses as strong antioxidant, anti-inflammatory and antiproliferative properties. Recently, we have shown that oral feeding of pomegranate fruit extract (PFE) to mice afforded substantial protection from the adverse effects of single UVB radiation via modulation in early biomarkers of photocarcinogenesis. This study was designed to investigate the photochemopreventive effects of PFE (0.2%, wt/vol) after multiple UVB irradiations (180 mJ cm(-2), on alternative day, for a total of seven treatments) to the skin of SKH-1 hairless mice. Oral feeding of PFE to SKH-1 mice inhibited UVB-induced epidermal hyperplasia, infiltration of leukocytes, protein oxidation and lipid peroxidation. Immunoblot analysis demonstrated that oral feeding of PFE to mice inhibited UVB-induced (1) nuclear translocation and phosphorylation of nuclear factor kappa B/p65, (2) phosphorylation and degradation of IκBα, (3) activation of IKKα/ΙΚΚβ and (4) phosphorylation of mitogen-activated protein kinase proteins and c-Jun. PFE consumption also inhibited UVB-induced protein expression of (1) COX-2 and iNOS, (2) PCNA and cyclin D1 and (3) matrix metalloproteinases-2,-3 and -9 in mouse skin. Taken together, these data show that PFE consumption afforded protection to mouse skin against the adverse effects of UVB radiation by modulating UVB-induced signaling pathways.

Oral infusion of pomegranate fruit extract inhibits prostate carcinogenesis in the TRAMP model

We earlier provided evidence that oral consumption of pomegranate fruit extract (PFE) inhibits prostate cancer (PCa) cell growth in nude mice. To ascertain convincing evidence of chemopreventive effects of PFE against PCa, its efficacy requires to be evaluated in animal models that closely emulate human disease. Here, we provide evidence of remarkable tumor growth inhibitory effects of PFE using the TRAMP model. Mice received 0.1 and 0.2% PFE, equivalent to 250 and 500 ml of pomegranate juice, in drinking water, starting at 6 weeks and examined at 12, 20 and 34 weeks of age. In water-fed group, 100% mice developed palpable tumors by 20 weeks compared with only 30 and 20% in the 0.1 and 0.2% PFE-supplemented groups, respectively. At 34 weeks, palpable tumors were observed in 70 of 0.1% and only 50 of 0.2% PFE-supplemented mice. Compared with median survival of 43 weeks in water-fed mice, 0.1 and 0.2% PFE-supplemented mice exhibited median life expectancy of 73 and 92 weeks, respectively. Compared with respective water-fed groups, none of the mice in PFE-supplemented groups exhibited metastases to any of the distant organs at 20 weeks and only 20% mice exhibited metastasis at 34 weeks of age. Many of the PFE-supplemented animals had multiple foci of well-differentiated carcinoma but no evidence of poorly differentiated carcinoma. PFE supplementation resulted in simultaneous and significant inhibition of IGF-I/Akt/mTOR pathways in the prostate tissues and tumors. We suggest that pomegranate juice be evaluated in clinical trials in patients at high risk for developing PCa.

Oral Feeding of Pomegranate Fruit Extract Inhibits Early Biomarkers of UVB Radiation‐induced Carcinogenesis in SKH‐1 Hairless Mouse Epidermis

Pomegranate from the plant Punica granatum L. possesses strong antioxidant and anti-inflammatory properties. Recently, we have demonstrated that treatment of normal human epidermal keratinocytes with pomegranate fruit extract (PFE) inhibited UVB-mediated activation of nuclear factor kappa B (NF-κB) and mitogen activated protein kinases pathways. Here, we evaluated the effect of PFE on early biomarkers of photocarcinogenesis employing SKH-1 hairless mice. PFE was provided in drinking water (0.2%, wt/vol) to SKH-1 hairless mice for 14 days before a single UVB (180 mJ cm(-2)) irradiation. We found that oral feeding of PFE inhibited UVB-induced: (1) skin edema; (2) hyperplasia; (3) infiltration of leukocytes; (4) lipid peroxidation; (5) hydrogen peroxide generation; (6) ornithine decarboxylase (ODC) activity; and (7) ODC, cyclooxygenase-2 and proliferating cell nuclear antigen protein expression. Oral feeding of PFE enhanced repair of UVB-mediated formation of cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). Importantly, PFE treatment further enhanced UVB-mediated increase in tumor suppressor p53 and cyclin kinase inhibitor p21. Furthermore, oral feeding of PFE inhibited UVB-mediated: (1) nuclear translocation of NF-κB; (2) activation of IKKα; and (3) phosphorylation and degradation of IκBα. Taken together, we provide evidence that oral feeding of PFE to mice affords substantial protection from the adverse effects of UVB radiation via modulation in early biomarkers of photocarcinogenesis and provide suggestion for its photochemopreventive potential.

P18 Comparative effect of pomegranate extract (PFE) and sodium salicylate (NaSal) on SbCl-1 melanoma cellular proliferation

Introduction Acetylsalicylic acid (aspirin) were found to suppress growth in B16 melanoma cells. In addition farnesyl thiosalicylic acid (FTS) treatment was reported to significantly increase the proportion of apoptotic cells after 72 h. We recently showed that pomegranate fruit extract (PFE) possesses remarkable antitumor-promoting effects in mouse skin, PC3 prostate cancer cells and human A540 lung carcinoma. The purpose of this study was to compare the effect of NaSal and PFE on SbCl-1 melanoma cell viability and to explore their mechanism of action. Methods The effect of NaSal (Sigma, Germany) and PFE (Biotrek, Greece) on the viability of cells was determined by SLB assay. The SbCl-1 cells were plated in complete culture medium containing 150 μg/ml concentrations of PFE or 20 mmol/l final concentrations of NaSal in 96-well microtiter plates for 72 h. Results Our study of the antiproliferative effect of PFE and NaSal on SbCl-1 melanoma cells showed that both treatments resulted in a statistically significant decrease in cell viability relative to the control at 72 h, i.e. 81 and 86% respectively (P<0.001, one-way Analysis of variance ANOVA). However the decrease in cell viability between PFE and NaSal was not statistically significant at 72 h and was similar to the viability at incubation time zero (P>0.05, one-way Analysis of variance ANOVA). Conclusion It has been suggested that pomegranate extract may have a anti-proliferative effect in various human cancers. The extract contains certain species of flavonoids and anthocyanins. These species in other plants have shown anti-proliferative activity against human melanoma cells. In addition flavonoid-treatment of A375 cells led to sustained activation of p38 and JNK MAP kinases. On the other hand it has been reported that aspirin induces the activation of JNK and p38 in B16 cells, such as FTS of p38 in Colo853 cells. Finally our previous study showed that salicylic acid induced the activation of p38 in SbCl-1 melanoma cells. Taken together with the results of our present study strongly suggest that NaSal and PFE induce apoptotic death of SbCl-1 cells mediated by the same mechanism i.e. via the p38 and JNK cascade.

Abstract 951: Inhibition of lung tumorigenesis by oral consumption of pomegranate fruit extract

Abstract Lung cancer is the most common cause of cancer mortality worldwide and continues to be a major health problem, exceeding the combined mortality rates of colorectal, breast and prostate cancers. It has proven difficult to control lung cancer with conventional therapeutic and surgical approaches, and generally the prognosis is poor with an overall five-year survival rate of 10-14% in the USA. A competent approach to reduce the mortality from lung cancer is the early detection of premalignant lesions as the survival of early stage lung cancer patients is much better as compared to patients with advanced cancers. The current mainstays of lung cancer therapy are surgical resection, radiation ablation and systemic chemotherapy with considerable toxicity. However, it appears unlikely that these therapies can cause striking improvements in near future. Thus, effective approaches to the prevention of lung cancer need to be developed, especially efforts targeted to the progression of preneoplastic and benign neoplastic lesions to more malignant lung tumors. The pomegranate (Punica granatum; Punicaceae) fruit has been used for centuries in ancient cultures for its medicinal purposes and we have been defining the chemopreventive effects of pomegranate fruit extract (PFE). Based on MALDI-TOF MS analysis, PFE was found to contain anthocyanins (such as delphinidin, cyanidin and pelargonidin) and hydrolyzable tannins (such as punicalin, pedunculagin, punicalagin, gallagic and ellagic acid esters of glucose). We have earlier shown that PFE inhibits prosurvival signaling pathways in human lung carcinoma A549 cells and tumor growth in athymic nude mice (Carcinogenesis 2007;28:163-73) and A/J mice (Cancer Res 2007;67:3475-82). In this study, the chemopreventive activity of PFE during progression of lung adenomas was investigated in two mouse tumor protocols. Female A/J mice were treated with 0.2% PFE in drinking water (w/v, equivalent of human consumption of juice derived from two fruits) till the termination of the experiment. One week after treatment with PFE, mice were given a single i.p. injection of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) at dose of 100 mg/kg body weight or urethane at dose of 1 mg/g body weight. Mice were sacrificed at 16 weeks after NNK treatment and 20 weeks after treated with urethane. PFE administration significantly reduced the lung tumor multiplicity by 47% in mice treated with NNK and 52% in urethane-treated mice. Markers of cell proliferation, apoptosis and angiogenesis were studied by immunohistochemical staining. Treatment with PFE caused significant reduction in Ki-67, proliferating cell nuclear antigen (PCNA), caspase-3, CD-31 and vascular endothelial growth factor (VEGF) in lungs of mice treated with NNK and urethane. Thus, our results show that PFE can act as a chemopreventive agent in smokers and ex-smokers with early lung lesions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 951.

Stimulation of osteoblastic differentiation and inhibition of interleukin‐6 and nitric oxide in MC3T3‐E1 cells by pomegranate ethanol extract

In this experiment, we studied the effects of pomegranate fruit extract (PE) on the function of osteoblastic MC3T3-E1 cells and the production of local factors in osteoblasts. PE (16 approximately 250 microg/ml) significantly increased the growth of MC3T3-E1 cells (P < 0.05). Moreover, PE (50 microg/ml) caused a significant elevation of alkaline phosphatase (ALP) activity and collagen content in the cells. We then examined the effect of PE on the TNF-alpha-induced production of interleukin-6 (IL-6) and nitric oxide (NO) in osteoblasts. Treatment with PE (10 approximately 50 microg/ml) decreased the TNF-alpha (10(-10) M)-induced production of IL-6 and NO in osteoblasts.

The influence of pomegranate fruit extract in comparison to regular pomegranate juice and seed oil on nitric oxide and arterial function in obese Zucker rats

Metabolic syndrome includes most widely distributed clinical conditions such as obesity, hypertension, dislipidemia, and diabetes. Pomegranate fruit extract (PFE), rich in polyphenolic antioxidants, reduces the expression of oxidation-sensitive genes at the sites of perturbed shear-stress. The aim of this study was to evaluate the effect of PFE in comparison to regular pomegranate juice (PJ) and seed oil on the biological actions of nitric oxide (NO) and the arterial function in obese Zucker rats, a model of metabolic syndrome. Our results indicated that supplementation with PFE or PJ significantly decreased the expression of vascular inflammation markers, thrombospondin (TSP), and cytokine TGFβ1 ( P < 0.05), whereas seed oil supplementation had a significant effect only on TSP-1 expression ( P < 0.05). Plasma nitrate and nitrite (NO x ) levels were significantly increased by PFE and PJ ( P < 0.05). Furthermore, the effect of PFE in increasing endothelial NO synthase (eNOS) expression was comparable to that of PJ. These data highlight possible clinical applications of PFE in metabolic syndrome.