The effects of pomegranate consumption on blood pressure in adults: A systematic review and meta-analysis.

Considering the main component of cardiovascular disease and due to the high prevalence of hypertension, controlling blood pressure is required in individuals with various health conditions. Randomized clinical trials (RCTs) which studied the effects of pomegranate consumption on blood pressure have shown inconsistent findings. As a result, we intended to assess the effects of pomegranate consumption on systolic (SBP) and diastolic (DBP) blood pressure in adults. Systematic literature searches up to January 2024 were carried out using electronic databases, including PubMed, Web of Science, and Scopus, to identify eligible RCTs assessing the effects of pomegranate on blood pressure as an outcome. All the individuals who took part in our research were adults who consumed pomegranate in different forms as part of the study intervention. Heterogeneity tests of the selected trials were performed using the I2 statistic. Random effects models were assessed based on the heterogeneity tests, and pooled data were determined as the weighted mean difference (WMD) with a 95% confidence interval (CI). Of 2315 records, 22 eligible RCTs were included in the current study. Our meta-analysis of the pooled findings showed that pomegranate consumption significantly reduced SBP (WMD: -7.87 mmHg; 95% CI: -10.34 to -5.39; p < 0.001) and DBP (WMD: -3.23 mmHg; 95% CI: -5.37 to -1.09; p = 0.003). Individuals with baseline SBP > 130 mmHg had a significantly greater reduction in SBP compared to individuals with baseline SBP < 130 mmHg. Also, there was a high level of heterogeneity among studies (SBP: I2 = 90.0% and DBP: I2 = 91.8%). Overall, the results demonstrated that pomegranate consumption lowered SBP and DBP in adults. Although our results suggest that pomegranate juice may be effective in reducing blood pressure in the pooled data, further high-quality studies are needed to demonstrate the clinical efficacy of pomegranate consumption.

Effects of crocin on inflammatory biomarkers and mental health status in patients with multiple sclerosis: A randomized, double-blinded clinical trial.

BACKGROUND: Multiple sclerosis (MS), as a demyelinating disease correlated with inflammation and oxidative stress, affects the central nervous system and causes a wide range of complications, including psychiatric disorders. Considering the anti-inflammatory and antioxidant properties associated with the bioactive components of saffron, such as crocin (trans-crocetin bis(ß-d-gentiobiosyl) ester), and their potential impact on ameliorating psychiatric symptoms, our study aimed to investigate the effect of crocin on biomarkers of inflammation, oxidative stress, and mental health, e.g., depression and anxiety in individuals with MS. METHOD: Patients with MS were randomized into two groups, taking either 15 mg crocin tablets twice a day (n = 25; 30 mg/day) or placebo tablets (n = 25) for 8 weeks. The valid and reliable Beck depression and anxiety scale questionnaire was recorded, and fasting blood samples were collected to measure biomarkers, including high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and nitric oxide (NO) at baseline and week 8 following the intervention. RESULTS: The data analysis using ANCOVA showed that supplementation with crocin for 8 weeks significantly lowered hs-CRP levels (p-value= 0.01). In addition, within-group comparisons showed crocin significantly decreased anxiety (p-value= 0.01). However, crocin did not affect serum MDA and NO after 8 weeks of intervention. CONCLUSION: Our findings suggest that crocin may keep promise in attenuating inflammation, evidenced by reducing hs-CRP in patients with MS. However, supplementation for 8 weeks may not be sufficient to improve mental health, and future clinical studies with higher sample sizes and various doses and durations are recommended.

The effects of pomegranate consumption on liver function enzymes in adults: A systematic review and meta-analysis.

BACKGROUND: We performed a systematic review and meta-analysis of all published clinical trial studies to provide a more accurate estimation of pomegranate effects on liver enzymes in different clinical conditions. METHODS: A systematic literature search was carried out using electronic databases, including PubMed, Web of Science, and Scopus, up to March 2023 to identify eligible randomized clinical trials (RCTs) evaluating the effect of pomegranate consumption on liver function enzymes. Heterogeneity tests of the selected trials were performed using the I2 statistic. Random effects models were assessed based on the heterogeneity tests, and pooled data were determined as the weighted mean difference with a 95% confidence interval. RESULTS: Out of 3811 records, 9 eligible RCTs were included in the current study. However, there are limitations in the included studies, which can be mentioned in the dose, duration, and type of interventions that are different among the studies, as well as the small number of included studies. All this causes heterogeneity among studies and this heterogeneity limits the consistency of the results. Our meta-analysis showed that pomegranate intake had a significant effect on lowering aspartate aminotransferase (AST) levels in long-term intervention (> 8 weeks), obese (BMI≥30) individuals, or patients with metabolic disorders. Furthermore, results showed a significant decrease in alanine aminotransferase (ALT) levels in the long-term intervention (> 8 weeks) or in patients with metabolic disorders following the pomegranate intake. Combined results from the random-effects model indicated a significant reduction in gamma-glutamyl transferase (GGT) levels (WMD: -5.43 IU/L 95% CI: -7.78 to -3.08; p < 0.001;) following the pomegranate intake. The results of Egger's test mentioned a significant publication bias for the trials examining the effect of pomegranate intake on AST (p = 0.007) and ALT (p = 0.036). CONCLUSION: Our results suggest that long-term pomegranate intake may be effective in ameliorating liver enzymes in adults with obesity and metabolic disorders who are more likely to have elevated baseline liver enzymes due to some degree of liver injury or tissue damage. However, some studies failed to conduct independent biochemical characterization of the product used, including the presence and quantity of polyphenols, antioxidants, and proanthocyanidins.

The effects of pomegranate consumption on inflammatory and oxidative stress biomarkers in adults: a systematic review and meta-analysis.

BACKGROUND: Several studies have shown the effects of pomegranate on oxidative stress and inflammation biomarkers, while some studies showed no effects of pomegranate on these biomarkers. Therefore, we aimed to evaluate the effects of pomegranate consumption on C-reactive protein (CRP), interlukin-6 (IL-6), tumor necrosis factor α (TNF-α), total antioxidant capacity (TAC), and malondialdehyde (MDA) in adults. METHODS: A systematic literature search was performed using databases, including PubMed, Web of Science, and Scopus, up to May 2023 to identify eligible randomized controlled trials (RCTs). Heterogeneity tests of the included trials were performed using the I2 statistic. Random effects models were assessed based on the heterogeneity tests, and pooled data were determined as the weighted mean difference with a 95% confidence interval. RESULTS: Of 3811 records, 33 eligible RCTs were included in the current study. Our meta-analysis of the pooled findings showed that pomegranate consumption significantly reduced CRP (WMD: -0.50 mg/l; 95% CI -0.79 to -0.20; p = 0.001), IL-6 (WMD: -1.24 ng/L 95% CI -1.95 to -0.54; p = 0.001), TNF-α (WMD: -1.96 pg/ml 95%CI -2.75 to -1.18; p < 0.001), and MDA (WMD: -0.34 nmol/ml 95%CI -0.42 to -0.25; p < 0.001). Pooled analysis of 13 trials revealed that pomegranate consumption led to a significant increase in TAC (WMD: 0.26 mmol/L 95%CI 0.03 to 0.49; p = 0.025). CONCLUSION: Overall, the results demonstrated that pomegranate consumption has beneficial effects on oxidative stress and inflammatory biomarkers in adults. Therefore, pomegranate can be consumed as an effective dietary approach to attenuate oxidative stress and inflammation in patients with cardiovascular diseases. PROSPERO REGISTRATION CODE: CRD42023406684.

Saliva insulin tracks plasma insulin across the day following high-carbohydrate and low-carbohydrate meals.

Non-invasive monitoring of insulin could hold promise to identify those with, or at risk for developing, insulin resistance. We aimed to examine saliva insulin responses across the day following high- and low-carbohydrate meals and evaluate whether changes in saliva insulin might accurately reflect changes in plasma insulin. In two randomized crossover studies, young normal weight men (NW; n = 8; Study 1) and adults with overweight/obesity (OO; n = 8; Study 2) completed two 9-h experimental trials in which the participants consumed isocaloric mixed high-carbohydrate (HC) or low-carbohydrate (LC) meals at 0, 3, and 6 h. Plasma and saliva samples were collected at fasted baseline and every 30 min for a total of 19 samples across 9 h. Overall, findings revealed a similar trend for postprandial saliva and plasma insulin responses regardless of the time of the day with a ∼30-45 min lag between saliva and plasma insulin responses. In both NW and OO groups, saliva and plasma insulin area under the curve (AUC) and incremental AUC were significantly higher in HC condition as compared to LC condition (all P ≤ 0.002). Nine-hour plasma and saliva insulin total AUCs were strongly and very strongly correlated in both HC (r = 0.68; P = 0.007) and LC (r = 0.84, P < 0.001) conditions, respectively. Saliva insulin is proportionate to and appears to reasonably track plasma insulin across the day with a ∼30-45 min delay. Saliva insulin shows promise as a non-invasive method to discern between low and high plasma insulin and may have utility in predicting the degree of insulin resistance (NCT03374436).

A Green Approach for the Biosynthesis of Gold Nanoparticles Using Cuminum cyminum L. Seed and Its Application for Pain Management in Rats.

Background: This study investigated the antinociceptive effect of cumin and its biosynthesized gold nanoparticles (AuNPs). Methods: Cumin extract (E) and cumin-AuNPs (GN) were prepared and administered intraperitoneally at the concentrations of 200, 500, and 1000 mg/ml to 27 male rats. Ultraviolet-visible spectroscopy and atomic force microscopy were applied for AuNPs synthesis confirmation. The nociceptive behavior was assessed, and IL-6 serum levels were measured. Results: Cumin-AuNPs showed a peak absorption of 515 nm, and a size of about 40 nm. Three different concentrations of extract had no significant effect on acute and chronic nociceptive behavior. GN + E200 (46.00 ± 10.59) showed a significant acute anti-nociceptive effect compared to the control (98.66 ± 4.91; p = 0.029) and SS300 (98.33 ± 20.30; p = 0.029) groups. Also, GN + E500 (42.00 ± 11.84) significantly reduced acute nociceptive behavior compared to the control (98.66 ± 4.91; p = 0.019), SS300 (98.33 ± 20.30; p = 0.020), and GN + E1000 (91.00 ± 26.00; p = 0.040) groups. IL-6 serum levels reduced significantly in GN + E500 (24.65 ± 10.38; p = 0.002) and SS300 (33.08 ± 1.68; p = 0.039) compared to the controls (46.24 ± 3.02). Chronic nociceptive behavior was significantly lower in the SS300 (255.33 ± 26.30) compared to E200 (477.00 ± 47.29; p = 0.021), E500 (496.25 ± 46.29; p = 0.013), and GN + E500 (437.00 ± 118.03; p = 0.032) groups. Conclusion: Our findings suggest the potential effects of cumin-AuNPs on formalin-induced nociceptive behavior, which is independent of IL-6serum levels.

Metabolic Effect of Breaking Up Prolonged Sitting with Stair Climbing Exercise Snacks.

PURPOSE: Prolonged sitting is associated with cardiometabolic complications. The study purpose was to investigate whether breaking up prolonged sitting with brief stair climbing exercise "snacks" could lower postprandial insulin, glucose, and free fatty acids responses. METHODS: In two separate randomized crossover studies, 12 young healthy-weight men (study 1) and 11 adults with overweight/obesity (OW; study 2) completed two experimental conditions: i) sedentary (SED; 9-h sitting) and ii) stair climbing snacks (SS; 8 × 15-30 s once per hour). The same high-glycemic index meals were consumed at 0, 3, and 6 h at each condition. The primary outcome was total insulin area under the curve (AUC) across 9 h. RESULTS: In healthy-weight men, there were no significant differences between SS and SED for total (9-h) insulin AUC (P = 0.24, d = 0.4), total glucose AUC (P = 0.17, d = 0.48), total nonesterified fatty acid (NEFA) AUC (P = 0.22, d = 0.4), or total triglyceride AUC (P = 0.72). In adults with OW, total insulin AUC (-16.5%, P = 0.036, d = 0.94) and total NEFA AUC (-21%, P = 0.016, d = 1.2) were significantly lower in SS versus SED. No differences were found for total glucose and triglyceride AUC (all, P > 0.31) in participants with OW. CONCLUSIONS: Breaking up 9 h of prolonged sitting with hourly brief stair climbing exercise snacks lowered postprandial insulin and NEFA levels in adults with overweight/obesity.

Increased mitochondrial content and function by resveratrol and select flavonoids protects against benzo[a]pyrene-induced bioenergetic dysfunction and ROS generation in a cell model of neoplastic transformation.

Dietary polyphenols act in cancer prevention and may inhibit carcinogenesis. A possible mitochondrial mechanism for carcinogen-induced neoplastic transformation and chemoprevention by polyphenols, however, is largely unexplored. Using the Bhas 42 cell model of carcinogen-induced neoplastic transformation, we investigated benzo[a]pyrene (B[a]P) along with different polyphenols for their effects on mitochondrial content and function, and on mitochondrial and intracellular ROS generation. Bhas 42 cells were either co-treated with 5 µM polyphenol starting 2 h before exposure to 4 µM B[a]P for 24 or 72 h, or pre-treated with polyphenol for 24 h and removed prior to B[a]P exposure. Exposure to B[a]P decreased mitochondrial content (by 46% after 24 h and 30% after 72 h), decreased mitochondrial membrane potential and cellular ATP, and increased generation of mitochondrial superoxide and intracellular ROS. Polyphenol co-treatments protected against the decreased mitochondrial content, with resveratrol being the most effective (increasing the mitochondrial content after 72 h by 75%). Measurements after 24 h of mRNA for mitochondria-related proteins and of SIRT1 enzyme activity suggested an involvement of increased mitochondrial biogenesis in the polyphenol effects. The polyphenol co-treatments also ameliorated B[a]P-induced deficits in mitochondrial function (most strongly resveratrol), and increases in generation of mitochondrial superoxide and intracellular ROS. Notably, 24 h pre-treatments with polyphenols strongly suppressed subsequent B[a]P-induced increases, after 24 and 72 h, in mitochondrial superoxide and intracellular ROS generation, with resveratrol being the most effective. In conclusion, the results support a mechanism for B[a]P carcinogenesis involving impaired mitochondrial function and increased mitochondria-derived ROS, that can be ameliorated by dietary polyphenols. The evidence supports an increase in mitochondrial biogenesis behind the strong chemoprevention by resveratrol, and a mitochondrial antioxidant effect in chemoprevention by quercetin.

Phenolic Breakdown Products of Cyanidin and Quercetin Contribute to Protection against Mitochondrial Impairment and Reactive Oxygen Species Generation in an In Vitro Model of Hepatocyte Steatosis.

A question in cell culture and dietary studies on protection by flavonoids against conditions such as hepatocyte steatosis is whether effects might be due to phenolic breakdown/digestion products. In HepG2 hepatocytes, treatment with quercetin, cyanidin, or their phenolic breakdown/digestion products (protocatechuic acid, 2,4,6-trihydroxybenzaldehyde, and caffeic acid), starting 2 h prior to oleic acid for 24 h, protected similarly against increases in intracellular lipid and reactive oxygen species and decreased mitochondrial membrane potential. Cyanidin or the phenolic products also protected against decreased mitochondrial content. After preincubation for only 1 h (to limit spontaneous degradation) and removal prior to oleic acid, only the phenolic products protected against decreased mitochondrial content, and without adding oleic acid, only protocatechuic acid and caffeic acid, and less so cyanidin, induced mitochondrial content. The results suggest that phenolic breakdown/digestion products of cyanidin and quercetin contribute to the protective effects in vitro, and perhaps in vivo.

Dietary Polyphenols Protect Against Oleic Acid-Induced Steatosis in an in Vitro Model of NAFLD by Modulating Lipid Metabolism and Improving Mitochondrial Function.

In this study, we aimed to determine the relative effectiveness of common dietary polyphenols or the isoquinoline alkaloid berberine in protecting against molecular mechanisms underlying non-alcoholic fatty liver disease (NAFLD) involving changes to cellular lipid metabolism and bioenergetics. In a model of steatosis using HepG2 hepatocytes, exposure of the cells to 1.5 mM oleic acid (OA) for 24 h caused steatosis and distorted cell morphology, induced the expression of mRNA for enzymes that are involved in lipogenesis and fatty acid oxidation (FAS and CPT1A), and impaired indices of aerobic energy metabolism (PPARγ mRNA expression, mitochondrial membrane potential (MMP), and galactose-supported ATP production). Co-treatment with 10 µM of selected polyphenols all strongly protected against the steatosis and changes in cell morphology. All polyphenols, except cyanidin, inhibited the effects on FAS and PPARγ and further increased CPT1A1 expression, suggesting a shift toward increased ß-oxidation. Resveratrol, quercetin, catechin, and cyanidin, however not kuromanin or berberine, ameliorated the decreases in MMP and galactose-derived ATP. Berberine was unique in worsening the decrease in galactose-derived ATP. In further investigations of the mechanisms involved, resveratrol, catechin, and berberine increased SIRT1 enzyme activity and p-AMPKαThr172 protein, which are involved in mitochondrial biogenesis. In conclusion, selected polyphenols all protected against steatosis with similar effectiveness, however through different mechanisms that increased aerobic lipid metabolism and mitochondrial function.

Polyphenol inhibition of benzo[a]pyrene-induced oxidative stress and neoplastic transformation in an in vitro model of carcinogenesis.

While dietary polyphenols are widely recognized for cancer-preventing characteristics, the relative effectiveness and mechanisms of action of different polyphenols is not clear. In the present study, we investigated the protective effects of six different polyphenols against benzo[a]pyrene (B[a]P)-induced oxidative stress and neoplastic transformation in the Bhas 42 cell carcinogenesis assay. All of the polyphenols completely prevented the increased intracellular ROS generation by B[a]P at 12 h, and most inhibited after 3 days. B[a]P increased mitochondrial superoxide generation at 12 h, which was inhibited by the anthocyanins and berberine. B[a]P increased expression of genes related to oxidative stress and inflammation (Nrf2, UCP2, and TNF-α) after 24 h. Polyphenols strongly inhibited the increase in TNF-α and also several polyphenols inhibited the increase in UCP2. At 21 days after 72 h treatment, B[a]P produced a large increase in the number of neoplastic colonies. This transformation was inhibited by most polyphenols, and strongly by resveratrol. In summary, all tested polyphenols were able to inhibit B[a]P-induced increases in markers of oxidative stress and inflammation, and to inhibit cellular transformation, with resveratrol being notable for the strongest preventive effect on cell transformation. The results support a role for dietary polyphenols in protecting against B[a]P-induced carcinogenesis.

Comparison of dietary polyphenols for protection against molecular mechanisms underlying nonalcoholic fatty liver disease in a cell model of steatosis.

SCOPE: Dietary polyphenols have shown promise in protecting the liver against nonalcoholic fatty liver disease. The relative effectiveness and mechanisms of different polyphenols however is mostly unknown. METHODS AND RESULTS: In a model of steatosis using HepG2 hepatocytes, we evaluated the protective effects of different classes of polyphenols and the contributing mechanisms. The treatment of the cells with oleic acid increased reactive oxygen species (ROS) generation and expression of tumor necrosis factor alpha (TNF-α), decreased expression of uncoupling protein 2, and decreased mitochondrial content and markers of biogenesis. The treatment with 1-10 µM polyphenols (resveratrol, quercetin, catechin, cyanidin, kuromanin, and berberine), as well as phenolic degradation products (caffeic acid, protocatechuic acid, and 2,4,6-trihydroxybenzaldehyde), all protected by more than 50% against the oleic acid induced increase in ROS. In other mechanisms involved, the polyphenols except anthocyanins strongly prevented or reversed the effect on mitochondrial content/biogenesis, increased expression of manganese superoxide dismutase, and prevented the large increase in TNF-α expression. Most polyphenols also prevented the decrease in uncoupling protein 2. The anthocyanins were unique in decreasing ROS generation without inducing mitochondrial biogenesis or manganese superoxide dismutase expression. CONCLUSION: While different polyphenols similarly decreased cellular ROS in this model of steatosis, they differed in their ability to suppress TNF-α expression and induce mitochondrial biogenesis and content.

Green Tea (Camellia sinensis) Supplementation to Diabetic Rats Improves Serum and Hepatic Oxidative Stress Markers.

Diabetes is one of the most common metabolic disorders and is interrelated to oxidative stress-induced diseases. According to the role of dietary antioxidants in control and prevention of diabetes, this study was aimed to evaluate the effect of green tea extract on serum glucose levels and serum and hepatic total antioxidant capacity (TAC) and lipid (MDA) in diabetic rats. Experimental diabetes in rats was induced by intraperitoneal injection of streptozotocin (55 mg/Kg). Alcoholic extract of green tea (100, 200 mg/Kg) was given by oral gavage to normal and diabetic rats for 4 weeks. Finally, serum glucose and serum and hepatic levels of MDA and TAC were measured and analyzed statistically. Data showed that green tea extract at dose of 200 mg/Kg significantly decreased the serum glucose levels, serum and hepatic MDA concentration and increased the total antioxidant capacity in diabetic rats (p < 0.05). Green tea supplementation also increased hepatic TAC in normal rats (p < 0.05). The antihyperglycemic and antioxidative features of green tea make it an attractive candidate for the prophylactic treatment of diabetes, although further investigation is needed to determine exact dose and duration of supplementation.

Effect of green tea extract on body weight, serum glucose and lipid profile in streptozotocin-induced diabetic rats. A dose response study.

OBJECTIVE: To examine the effect of green tea extract on body weight, serum levels of glucose, and lipids in streptozotocin-induced diabetic rats. METHODS: This experimental study was carried out in the Diabetes Research Center, Ahvaz University of Medical Sciences, Ahvaz, Iran from January 2011 to March 2011. Forty-eight male wistar rats (200-250 g) were divided randomly into 6 groups. Diabetes was induced by a single intraperitoneal injection of stereptozotocin (55 mg/kg). The experimental groups received alcohol extract of green tea leaves (100 mg/kg and 200 mg/kg) for 4 weeks and the body weight of animals were measured every day. Finally, blood samples were collected and analyzed for glucose and lipid profile levels. RESULTS: Administration of green tea extract caused a significant decrease in serum glucose and total cholesterol levels and significantly improved the body weight loss in diabetic rats treated with 200 mg/kg green tea in comparison to diabetic control group. No significant changes were observed in triglyceride (p=0.04), low-density-lipoprotein cholesterol (p=0.000), and high-density-lipoprotein cholesterol levels (p=0.01) following intervention. CONCLUSION: It appears that green tea extract had both antihyperglycemic and hypocholesterolmic effects in diabetic rats, although further work is needed to determine their mechanism.

Effect of daidzein-low-calorie diet on body weight, serum levels of glucose, resistin, and high sensitive C-reactive protein in high fat, high calorie diet induced rats.

OBJECTIVE: To assess the effect of restricting calories with or without daidzein on weight, serum levels of glucose, and inflammatory markers in obese rats. METHODS: This experimental study was carried out in Jundishapur University, Ahvaz, Iran, from September 2010 to January 2011. Obesity was induced in 30 male Wistar rats (140-160, 6-8 weeks age) after 6 weeks by feeding them a high-fat diet. Then, the rats were divided into 3 groups: obese rats treated with low-calorie diet containing 50 mg/kg daidzein (n=10); obese rats treated with low-calorie diet containing dimethyl sulfoxide (n=10); and obese rats that were given ad libitum access to food as the control group (n=10). After 4 weeks, blood samples were collected in order to analyze the levels of glucose, resistin, and high sensitive C-reactive protein (CRP). RESULTS: Restriction of calories resulted in decreased blood glucose (p=0.002), and decreased levels of high sensitive CRP (p=0.000), but had no significant effect on resistin level. Daidzein administration had no significant effect on body weight, serum glucose, levels of resistin, and high sensitive CRP. CONCLUSION: Calorie restriction significantly affected body weight, serum glucose, low-grade inflammation biomarkers, and masked the effect of daidzein.