Involvement of Aryl Hydrocarbon Receptor in Longevity and Healthspan: Insights from Humans, Mice, and C. elegans.

In previous studies, using transcriptomic analysis, we observed higher levels of aryl hydrocarbon receptor (AHR) gene expression in the peripheral blood cells of centenarians compared to octogenarians. This suggests the potential significance of this receptor in maintaining physiological balance and promoting healthy aging, possibly linked to its critical role in detoxifying xenobiotics. In our current study, we confirmed that AHR expression is indeed higher in centenarians. We employed C. elegans as a model known for its suitability in longevity studies to explore whether the AHR pathway has a significant impact on lifespan and healthspan. Our survival assays revealed that two different mutants of AHR-1 exhibited lower longevity. Additionally, we used a mouse model to examine whether supplementation with pomegranate extract modulates the expression of AHR pathway genes in the liver. Furthermore, we studied a nutritional strategy based on pomegranate extract administration to investigate its potential modulation of life- and healthspan in worms.

Antimicrobial Potential of Pomegranate and Lemon Extracts Alone or in Combination with Antibiotics against Pathogens.

Amidst the growing concern of antimicrobial resistance as a significant health challenge, research has emerged, focusing on elucidating the antimicrobial potential of polyphenol-rich extracts to reduce reliance on antibiotics. Previous studies explored the antifungal effects of extracts as potential alternatives to conventional therapeutic strategies. We aimed to assess the antibacterial and antifungal effects of standardised pomegranate extract (PE) and lemon extract (LE) using a range of Gram-negative and Gram-positive bacteria and two yeast species. Additionally, we assessed the antimicrobial activities of common antibiotics (Ciprofloxacin, Imipenem, Gentamicin, and Ceftazidime), either alone or in combination with extracts, against Staphylococcus aureus and Escherichia coli. PE displayed substantial antibacterial (primarily bactericidal) and antifungal effects against most pathogens, while LE exhibited antibacterial (mostly bacteriostatic) and antifungal properties to a lesser extent. When compared with antibiotics, PE showed a greater zone of inhibition (ZOI) than Ciprofloxacin and Ceftazidime (p < 0.01) and comparable ZOI to Gentamicin (p = 0.4) against Staphylococcus aureus. However, combinations of either PE or LE with antibiotics exhibited either neutral or antagonistic effects on antibiotic activity against Staphylococcus aureus and Escherichia coli. These findings contribute to the existing evidence regarding the antimicrobial effects of PE and LE. They add to the body of research suggesting that polyphenols exert both antagonistic and synergistic effects in antimicrobial activity. This highlights the importance of identifying optimal polyphenol concentrations that can enhance antibiotic activity and reduce antibiotic resistance. Further in vivo studies, starting with animal trials and progressing to human trials, may potentially lead to recommendation of these extracts for therapeutic use.

Pomegranate natural extract Pomanox® positively modulates skin health-related parameters in normal and UV-induced photoaging conditions in Hs68 human fibroblast cells.

Skin photoaging is primarily caused by ultraviolet radiation and can lead to the degradation of skin extracellular matrix components, resulting in hyperpigmentation and skin elasticity loss. In this area, polyphenols have become of great interest because of their antioxidant, anti-inflammatory and antiaging properties. Here, we evaluated the effects of the pomegranate natural extract Pomanox® on skin health-related parameters in normal and UV-induced photoaging conditions in human fibroblast Hs68 cells. Moreover, the inhibitory effects of Pomanox® on tyrosinase activity were assessed. In normal conditions, Pomanox® significantly modulated collagen and hyaluronic acid metabolisms. In UV-exposed cells, both preventive and regenerative treatments with Pomanox® positively modulated hyaluronic acid metabolism and decreased ROS levels. However, only the preventive treatment modulated collagen metabolism. Finally, Pomanox® showed a marked inhibitory capacity of tyrosinase activity (IC50 = 394.7 µg/mL). The modulation of skin health-related parameters exhibited by Pomanox® open a wide range of potential applications of this product.

Pomegranate (Punica granatum L.) and Its Rich Ellagitannins as Potential Inhibitors in Ulcerative Colitis.

Ulcerative colitis, an immune-mediated inflammatory disease of the gastrointestinal tract, places a significant financial burden on patients and the healthcare system. Recently, reviews of the pomegranate and the abundant medicinal applications of its ellagitannins, as well as its pharmacological action, phytochemicals, metabolism, and pharmacokinetics, have been completed. However, summaries on their anti-ulcerative colitis effects are lacking. Numerous preclinical animal investigations and clinical human trial reports demonstrated the specific therapeutic effects of pomegranate and the effect of its ellagitannins against ulcerative colitis. According to the literature collected by Sci-finder and PubMed databases over the past 20 years, this is the first review that has compiled references regarding how the rich ellagitannins found in pomegranate have altered the ulcerative colitis. It was suggested that the various parts of pomegranates and their rich ellagitannins (especially their primary components, punicalagin, and ellagic acid) can inhibit oxidant and inflammatory processes, regulate the intestinal barrier and flora, and provide an anti-ulcerative colitis resource through dietary management.

Efficacy of pomegranate extract loaded solid lipid nanoparticles transdermal emulgel against Ehrlich ascites carcinoma.

The purpose of this work was to incorporate an optimized pomegranate extract loaded solid lipid nanoparticles (PE-SLNs) formula in a transdermal emulgel to evaluate its anticancer effect. The prepared emulgel formulae were evaluated for their physicochemical properties. An ex vivo permeation study was done through mouse skin and the kinetic parameters were determined. Kinetic data showed that the ex vivo permeation of PE from SLNs transdermal emulgel through mouse skin followed non-Fickian diffusion transport. Further, in vivo study was done by applying the optimized PE-SLNs transdermal emulgel on mice skin bearing a solid form of Ehrlich ascites carcinoma (EAC) as well as free PE, control, placebo, and standard groups for comparison. In addition, histopathological examinations of the samples obtained from the EAC mice model were performed. The results proved that application of the selected PE-SLNs emulgel formulation on the mice skin bearing solid tumor revealed statistically significant anticancer effects.

Pomegranate Extract Augments Energy Expenditure Counteracting the Metabolic Stress Associated with High-Fat-Diet-Induced Obesity.

Obesity is associated to a low grade of chronic inflammation leading to metabolic stress, insulin resistance, metabolic syndrome, dislipidemia, cardiovascular disease, and even cancer. A Mediterranean diet has been shown to reduce systemic inflammatory factors, insulin resistance, and metabolic syndrome. In this scenario, precision nutrition may provide complementary approaches to target the metabolic alterations associated to "unhealthy obesity". In a previous work, we described a pomegranate extract (PomE) rich in punicalagines to augment markers of browning and thermogenesis in human differentiated adipocytes and to augment the oxidative respiratory capacity in human differentiated myocytes. Herein, we have conducted a preclinical study of high-fat-diet (HFD)-induced obesity where PomE augments the systemic energy expenditure (EE) contributing to a reduction in the low grade of chronic inflammation and insulin resistance associated to obesity. At the molecular level, PomE promotes browning and thermogenesis in adipose tissue, reducing inflammatory markers and augmenting the reductive potential to control the oxidative stress associated to the HFD. PomE merits further investigation as a complementary approach to alleviate obesity, reducing the low grade of chronic inflammation and metabolic stress.

Combination of pomegranate extract and curcumin ameliorates thioacetamide-induced liver fibrosis in rats: impact on TGF-ß/Smad3 and NF-κB signaling pathways.

Protection against liver injury and its consequences is considered an essential issue to minimize the number of annual deaths caused by liver diseases. The present study was designed to evaluate the potential role of pomegranate extract (PE) and/or curcumin in the regression of thioacetamide (TAA)-induced liver fibrosis, focusing on their modulatory effects on Nrf2/HO-1, NF-κB, and TGF-ß/Smad3 signaling pathways. Liver fibrosis was induced in male Wistar rats by intraperitoneal injection of TAA (100 mg/kg) three times a week, for 8 weeks. To assess the protective effects of PE and/or curcumin against TAA-induced liver fibrosis, rats were treated on a daily basis with oral doses of PE (200 mg/kg) and/or curcumin (200 mg/kg) for 8 weeks. The results indicated that PE and/or curcumin attenuated TAA-induced liver fibrogenesis, as evidenced by a significant improvement in the liver function tests (AST, ALT, ALP, and albumin), oxidative stress biomarkers (MDA, SOD, and GSH), and inflammatory biomarkers (NF-ĸB, TNF-α, IL-1ß, iNOS, TGF-ß, and MPO), compared to TAA group. Moreover, treatment with PE and/or curcumin exerted a significant upregulation of Nrf2/HO-1 gene expressions along with significant downregulation of NF-ĸB, TGF-ß, and phospho-Smad3 protein expressions, as well as α-SMA and collagen-1 gene expressions. The histopathological examination has corroborated these findings. In conclusion, hepatoprotective activities of PE and/or curcumin could be linked to their abilities to modulate Nrf2/HO-1, NF-κB, and TGF-ß/Smad3 signaling pathways. It is worth noting that the combination of PE and curcumin exerted superior hepatoprotective effects against TAA-induced liver fibrosis, as compared to monotherapy.

Effects of pomegranate supplementation on exercise performance and post-exercise recovery in healthy adults: a systematic review.

The functional significance of pomegranate (POM) supplementation on physiological responses during and following exercise is currently unclear. This systematic review aimed (i) to evaluate the existing literature assessing the effects of POM supplementation on exercise performance and recovery; exercise-induced muscle damage, oxidative stress, inflammation; and cardiovascular function in healthy adults and (ii) to outline the experimental conditions in which POM supplementation is more or less likely to benefit exercise performance and/or recovery. Multiple electronic databases were used to search for studies examining the effects of POM intake on physiological responses during and/or following exercise in healthy adult. Articles were included in the review if they investigated the effects of an acute or chronic POM supplementation on exercise performance, recovery and/or physiological responses during or following exercise. The existing evidence suggests that POM supplementation has the potential to confer antioxidant and anti-inflammatory effects during and following exercise, to improve cardiovascular responses during exercise, and to enhance endurance and strength performance and post-exercise recovery. However, the beneficial effects of POM supplementation appeared to be less likely when (i) unilateral eccentric exercise was employed, (ii) the POM administered was not rich in polyphenols (<1·69 g/l) and (iii) insufficient time was provided between POM-ingestion and the assessment of physiological responses/performance (≤1 h). The review indicates that POM has the potential to enhance exercise performance and to expedite recovery from intensive exercise. The findings and recommendations from this review may help to optimise POM-supplementation practice in athletes and coaches to potentially improve exercise-performance and post-exercise recovery.

Antibacterial Efficacy of Mouthwash Prepared from Pomegranate, Grape Seed and Guava Extracts against Oral Streptococci: An in Vivo Study.

BACKGROUND: Pomegranate, Grape seed and Guava extracts have much been reviewed in Ayurveda and has been proven to have antibacterial action Aim: The objective of the study is to investigate and compare the mouthwash prepared from pomegranate, grape seed and guava extracts on salivary streptococci levels at the end of 48 hr and 7 days, of twice a day usage. STUDY DESIGN: 40 school going children aged 8-10 yrs, randomly allocated into 4 groups (n=10 for experimental group) were asked to rinse with a) Mouthwash prepared from Pomegranate extract, 15 ml twice a day b) Mouthwash prepared from Grape seed extract, 15 ml twice a day, c) Mouthwash prepared from guava extract, 15 ml twice a day, d) Control- Distil water, twice a day. The oral streptococci colony forming units/ml (CFU/ml) was assessed by inoculating the salivary samples on blood agar media at the end of 48 hrs, and 7 days. RESULTS AND CONCLUSION: the aqueous extracts of the chosen herbal plants showed an acceptable antibacterial efficacy against oral streptococci.

Effect of lecithin nanoliposome or soybean lecithin supplemented by pomegranate extract on post-thaw flow cytometric, microscopic and oxidative parameters in ram semen.

This investigation was carried out to study the effect of soybean lecithin 1.5% (wt/vol) (0, 2.5, 5 and 7.5 mg l-1 pomegranate extract (PE)) or PE-loaded lecithin nanoliposome (0, 2.5, 5 and 7.5 mg l-1) to Tris-based extender. Sperm motility (CASA), viability, membrane integrity (HOS test), abnormalities, mitochondrial activity, apoptosis status, lipid peroxidation, total antioxidant capacity (TAC)) and antioxidant activities (GPX, SOD) were investigated following freeze-thawing. No significant differences were detected in motility parameters, viability, membrane integrity, and mitochondria activity after thawing sperm between soybean lecithin and lecithin nanoliposomes. It was shown that PE5 significantly improved sperm total and progressive motility, membrane integrity, viability, mitochondria activity, TAC and reduced lipid peroxidation (malondialdehyde concentration). Moreover, the percentage of apoptotic sperm in PE5 extenders was significantly the lowest among other treatments. Sperm abnormalities, SOD and GPX were not affected by the antioxidant supplements. For apoptotic status, no differences were observed between soybean lecithin and lecithin nanoliposome. We showed that lecithin nanoliposome extender can be a beneficial alternative extender to protect ram sperm during cryopreservation without any adverse effects. It was also observed that regarding pomegranate concentration, PE5 can improve the quality of ram semen after thawing.

Dietary pomegranate extract and inulin affect gut microbiome differentially in mice fed an obesogenic diet.

Growing evidence suggests that dysbiosis of gut microbiota is associated with pathogenesis of a variety of human diseases. Using dietary intervention to shape the composition and metabolism of the gut microbiota is increasingly recognized. In the present study, we investigated the effects of polysaccharide inulin and polyphenol-rich pomegranate extract (PomX) alone or in combination on the cecal microbiota composition and function in a diet induced obesity mouse model. Male C57BL/6 mice were randomly divided into four experimental groups and consumed either high-fat/high-sucrose [HF/HS (32% energy from fat, 25% energy from sucrose, 17% energy from protein)] diet, HF/HS diet supplemented with PomX (0.25%), or inulin (9%) or PomX and inulin in combination for 4 weeks. In mice fed the PomX-diet the proportion of Turicibacteraceae and Ruminococcaceae was significantly increased compared to the control HF/HS diet. Supplementation with inulin alone and inulin + PomX combination significantly increased the proportion of Verrucomicrobiaceae (A. muciniphila) and decreased Clostridiaceae. Only mice fed the inulin diet experienced an increase in serum lipopolysaccharide (LPS) and monocyte chemoattractant protein 1 (MCP-1), which was reversed when feeding the inulin + PomX diet. Feeding the inulin + PomX diet was associated with a significant increase in Bifidobacteriaceae and Rikenellaceae, which may have contributed to the reduction of endotoxemia markers. Inulin supplementation showed lower species richness of gut microbiota compared to mice fed with HF/HS or HF/HS/PomX, and the reduction was reversed by the addition of PomX. Inulin alone and in combination with PomX had distinct microbial clusters determined by both weighted and unweighted UniFrac Beta-Diversity principle coordinate analysis. A total of 19 KEGG biological pathways were significantly regulated in the gut microbiota with PomX and inulin alone or combined treatment. Inulin significantly enhanced KEGG infectious disease-related pathway associated with increase of serum LPS and MCP-1. No changes in gene expression of ileal proinflammatory cytokine and tight junction genes were observed in mice treated with PomX and inulin. Our results demonstrated that the gut microbiota and their biological pathways were differentially effected by dietary PomX and inulin fed combined or alone. It is therefore very important to consider the interaction among bioactive components of food when evaluating potential prebiotic effects.

Pomegranate ellagitannins stimulate the growth of Akkermansia muciniphila in vivo.

Results from our previous human pomegranate extract (POM extract) intervention study demonstrated that about seventy percent of participants were able to form urolithin A from ellagitannins in the intestine (urolithin A producers). Urolithin A formation was associated with a high proportion of Akkermansia muciniphila in fecal bacterial samples as determined by 16S rRNA sequencing. Here we investigated whether A. muciniphila counts increased in stool samples collected after the POM extract intervention compared to baseline stool samples using real-time PCR. In addition, we performed in vitro culture studies to determine the effect of POM extract and ellagic acid on the growth of A. muciniphila and to analyze ellagic acid metabolites formed in the culture broth by high-performance liquid chromatography. Supplementation of culture broth with 10 µM of ellagic acid did not change A. muciniphila growth while the addition of 0.18 mg/ml and 0.28 mg/ml of POM extract to the culture broth inhibited the growth of A. muciniphila significantly. Incubation of A. muciniphila with POM extract resulted in formation of ellagic acid and incubation of A. muciniphila with ellagic acid demonstrated hydrolysis of ellagic acid to metabolites different from urolithin A. The in vitro culture studies with A. muciniphila partially explain our in vivo findings that the presence of A. muciniphila was associated with breakdown of ellagic acid for further metabolism by other members of the microbiota. This is the first report of the role of A. muciniphila in ellagitannin hydrolysis. However, we conclude that enzymes from other bacteria must be involved in the formation of urolithin A in the human intestine.

Novel biopreservatives to enhance the safety and quality of strawberry juice.

Pomegranate extract, vanillin and geraniol were studied as natural antimicrobials on strawberry juice. Strawberry juice was treated with each agent at two concentrations: pomegranate extract at 180 and 360 µg/mL; vanillin at 2.5 and 5 mg/mL; and geraniol at 0.6 and 1.2 µL/mL. After being treated, juices were stored at 5 °C and microbiological, physicochemical and sensory studies were carried out. Also, a second batch of juice was inoculated with Escherichia coli O157:H7 (10(5) CFU/mL) before being treated, to safety study. Geraniol and vanillin, at both concentrations tested, were highly effective in reducing the native microflora on strawberry juice (more than 3 log cycles), extending the microbiological shelf-life of the product. Moreover, both antimicrobials improved the product safety by reducing inoculated E. coli O157:H7. Furthermore, vanillin showed a significant increase in polyphenol content compared to untreated juice. On the other hand, pomegranate extract applied at the highest concentration showed important reductions on mesophilic and psychrophilic bacteria, but no effect on yeast and molds and inoculated E. coli. Even though vanillin and geraniol incorporation on strawberry juice had a negative effect on its sensory quality, pomegranate extract had no impact on the sensory attributes evaluated. Combinations of the biopreservatives could be studied in order to decrease the concentration of the antimicrobials, reducing the effects on strawberry juice sensory characteristics.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Pomegranate ellagitannins stimulate growth of gut bacteria in vitro: Implications for prebiotic and metabolic effects.

The present study investigated the effect of pomegranate extract (POMx) and pomegranate juice (POM juice) on the growth of major groups of intestinal bacteria: Enterobacteriaceae, Bacteroides fragilis group, clostridia, bifidobacteria, and lactobacilli, and the utilization of pomegranate polyphenols by Bifidobacterium and Lactobacillus. The total phenolic content of the pomegranate extract and juice was determined using the Folin-Ciocalteau colorimetric method and reported as gallic acid equivalent (GAE). The polyphenol composition was determined by HPLC. Stool specimens were incubated with 400, 100, and 25 µg/ml GAE POMx and POM juice and subjected to selective culture. Bifidobacterium and Lactobacillus strains were incubated with 400 µg/ml GAE POMx and POM juice and metabolites were analyzed. POMx and POM juice increased the mean counts of Bifidobacterium and Lactobacillus and significantly inhibited the growth of B. fragilis group, clostridia, and Enterobacteriaceae in a dose-response manner. Bifidobacterium and Lactobacillus utilized ellagic acid and glycosyl ellagic acid but little or no punicalin was utilized. Neither POMx nor POM juice was converted to urolithins by the test bacteria or the in vitro stool cultures. The effect of pomegranate on the gut bacteria considered to be beneficial (Bifidobacterium and Lactobacillus) suggests that pomegranate may potentially work as a prebiotic. The concept that polyphenols such as those in pomegranate impact gut microbiota populations may establish a new role for polyphenols in human health.

Antiproliferative effects of pomegranate extract in MCF-7 breast cancer cells are associated with reduced DNA repair gene expression and induction of double strand breaks.

Pomegranate extract (PE) inhibits the proliferation of breast cancer cells and stimulates apoptosis in MCF-7 breast cancer cells. While PE is a potent antioxidant, the present studies were conducted to examine the mechanisms of action of PE beyond antioxidation by studying cellular and molecular mechanisms underlying breast tumorigenesis. PE inhibited cell growth by inducing cell cycle arrest in G2 /M followed by the induction of apoptosis. In contrast, antioxidants N-acetylcysteine and Trolox did not affect cell growth at doses containing equivalent antioxidant capacity as PE, suggesting that growth inhibition by PE cannot solely be attributed to its high antioxidant potential. DNA microarray analysis revealed that PE downregulated genes associated with mitosis, chromosome organization, RNA processing, DNA replication and DNA repair, and upregulated genes involved in regulation of apoptosis and cell proliferation. Both microarray and quantitative RT-PCR indicated that PE downregulated important genes involved in DNA double strand break (DSB) repair by homologous recombination (HR), such as MRE11, RAD50, NBS1, RAD51, BRCA1, BRCA2, and BRCC3. Downregulation of HR genes correlated with increased levels of their predicted microRNAs (miRNAs), miR-183 (predicted target RAD50) and miR-24 (predicted target BRCA1), suggesting that PE may regulate miRNAs involved in DNA repair processes. Further, PE treatment increased the frequency of DSBs. These data suggest that PE downregulates HR which sensitizes cells to DSBs, growth inhibition and apoptosis. Because HR represents a novel target for cancer therapy, downregulation of HR by PE may be exploited for sensitization of tumors to anticancer drugs.

Short communication: effect of pomegranate-residue supplement on Cryptosporidium parvum oocyst shedding in neonatal calves.

Cryptosporidium parvum is considered one of the most common enteropathogens, responsible for the high incidence of diarrhea and deleterious implications on immunity and health in neonatal calves. The pomegranate is well known for its health-promoting properties. Two experiments were designed to test the antiparasitical and antidiarrheal effects of concentrated pomegranate extract (CPE) supplement in milk in neonatal Holstein calves. Forty-one calves were randomly divided into control (n=20) and treatment (n=21) groups. For the first experiment, the treatment group was supplemented with 3.75% CPE in the daily milk ration, between 3 and 14 d of age, whereas the control group received only milk. Fecal samples were collected between d 5 and 13 to quantify Cryptosporidium oocysts, and the duration and intensity of diarrhea were evaluated. Reduced fecal oocyst count and diarrhea intensity and duration were revealed in the 3.75% CPE calves. No difference was noted in average daily gain between groups. In a second experiment, which was designed to test the effect of a lower CPE concentration (0.6% of daily milk allocation), no effects on fecal oocyst count and average daily gain were observed. However, compared with control, the lower CPE group was characterized by a shorter duration of diarrhea and higher weight gain among males at 14 d of age. These results suggest that the CPE supplement-to-calf milk ratio may potentially alleviate intestinal morbidity caused by Cryptosporidium.

Pomegranate extract inhibits the bone metastatic growth of human prostate cancer cells and enhances the in vivo efficacy of docetaxel chemotherapy.

BACKGROUND: Docetaxel treatment is the only first-line chemotherapy with a survival benefit in metastatic castration-resistant prostate cancer (PCa). Nonetheless, most patients become docetaxel resistant and inevitably progress with no cure. In this study, we investigated the potential of pomegranate extract (PE) in targeting metastatic castration-resistant PCa and improving docetaxel chemotherapy. METHODS: The in vitro and in vivo effect of POMx, a PE formula currently approved for clinical trials, in metastatic castration-resistant PCa cells was evaluated in experimental models. RESULTS: We demonstrated that POMx exhibited potent in vitro cytotoxicity in metastatic castration-resistant PCa cells. Mechanistic studies identified survivin as a novel molecular target that may mediate the anti-cancer activity of POMx, presumably through the inhibition of signal transducer and activator of transcription 3. The in vivo administration of POMx treatment effectively inhibited survivin, induced apoptosis, retarded C4-2 tumor growth in skeleton and significantly enhanced the efficacy of docetaxel in athymic nude mice. CONCLUSION: These results provide the first preclinical evidence that POMx may be effective in treating metastatic castration-resistant PCa and enhancing the efficacy of docetaxel chemotherapy. Prostate © 2013 Wiley Periodicals, Inc.

Characterization, Antimicrobial Activity, and Antioxidant Efficacy of a Pomegranate Peel Solution Against Persistent Root Canal Pathogens.

BACKGROUND: The limitations of dental irrigation solutions reinforce the need to explore novel bioactive compounds that are safer and biodegradable. This study aimed to prepare a 10% pomegranate peel solution (Punica granatum extract - PGE) and evaluate its antimicrobial and antioxidant effects for root canal treatment. METHODS: Lyophilized extracts (1g/10 mL) from pomegranate peels were prepared, and the punicalagin content was assessed by ultra-performance liquid chromatography using pure punicalagin (standard). The antimicrobial activity was tested against common persistent root canal pathogens by the agar diffusion method, minimum inhibitory concentration (MIC), and minimum bactericidal/fungicide concentration (MCB/MFC). The antioxidant activity (%AA) was assessed by the DPPH radical scavenging method. Data were analyzed by ANOVA and Tukey's test (α = 0.05). RESULTS: The total phenolic content of the PGEextract was 6.55 µg/mL. Differences were found among the inhibition zone of PGE (23.32 ± 3.65), 1% NaOCl (30.76 ± 4.73), and 50% ethanol (without inhibition) (p < 0.05). The MIC values of PGE ranged between 6.25 and 75 mg/ml, and PGE was effective against the tested pathogens. PGE had antioxidant potential (IC50 = 3.52 µg/mL); however, the mean values were inferior to that of the quercetin (positive control) (IC50 = 0.95 µg/mL). The DPPH scavenging effect (%AA) of PGE (70.98 ± 2.3) had no difference from the positive control (72.94 ± 2.1) (p = 0.253). CONCLUSION: The PGE extract was successfully biosynthesized and exhibited antimicrobial and antioxidant activity, suggesting its potential use as an adjuvant therapy during root canal treatment.

Pomegranate Extract Administration Reverses Loss of Motor Coordination and Prevents Oxidative Stress in Cerebellum of Aging Mice.

The cerebellum is responsible for complex motor functions, like maintaining balance and stance, coordination of voluntary movements, motor learning, and cognitive tasks. During aging, most of these functions deteriorate, which results in falls and accidents. The aim of this work was to elucidate the effect of a standardized pomegranate extract during four months of supplementation in elderly mice to prevent frailty and improve the oxidative state. Male C57Bl/6J eighteen-month-old mice were evaluated for frailty using the "Valencia Score" at pre-supplementation and post-supplementation periods. We analyzed lipid peroxidation in the cerebellum and brain cortex and the glutathione redox status in peripheral blood. In addition, a set of aging-related genes in cerebellum and apoptosis biomarkers was measured via real-time polymerase chain reaction (RT-PCR). Our results showed that pomegranate extract supplementation improved the motor skills of C57Bl/6J aged mice in motor coordination, neuromuscular function, and monthly weight loss, but no changes in grip strength and endurance were found. Furthermore, pomegranate extract reversed the increase in malondialdehyde due to aging in the cerebellum and increased the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio in the blood. Finally, aging and apoptosis biomarkers improved in aged mice supplemented with pomegranate extract in the cerebellum but not in the cerebral cortex.