BACKGROUND: Mouthwashes based on medicinal plants have demonstrated benefits in controlling plaque and inflammation, acting positively on the oral hygiene of patients with gingivitis. In traditional medicine, Punica granatum L. has been used to treat oral diseases in countries in Europe, Asia, North America, and Africa.
OBJECTIVE: The present study aimed to conduct a comprehensive review on the dental applications of Punica granatum L. for the treatment of gingivitis, including ethnomedicinal uses, analysis of randomized clinical trials, antibacterial activity against Porphyromonas gingivalis, mechanisms of action of phytochemicals isolated from this plant, and preclinical toxicity.
METHODS: The literature was retrieved from Google Scholar, PubMed®, SciELO, and ScienceDirect®, since the first report published on the topic in 2001 until March 2024.
RESULTS: Several clinical trials have demonstrated that mouthwashes containing P. granatum have equal or better efficacy than chlorhexidine in treating patients with gingivitis, confirming the indications for use of this plant by traditional communities. However, reports on the in vitro antibacterial activity of extracts from the fruits of this plant have not shown clinical relevance against the pathogen P. gingivalis. The ellagitannin punicalagin isolated from P. granatum has shown potential against several strains of Gram-positive and Gram-negative bacteria, but, to date, this compound has not yet been tested against P. gingivalis. It is likely that the mechanisms of action of flavonoids, such as quercetin, are involved in the inhibition of the activities of the RgpA, RgpB, and Kgp proteases of P. gingivalis.
CONCLUSIONS: In summary, natural products obtained from P. granatum do not present toxic side effects and can be considered as possible substitutes of commercial products recommended for the treatment of gingivitis and other oral diseases.

Nonalcoholic fatty liver disease (NAFLD) is a disorder in which excess fat accumulates in hepatocytes and can lead to serious complications. Oxidative stress is one of the leading causes of NAFLD. Pomegranates are considered antioxidant-rich fruit. This systematic review study was aimed to investigate the impact of pomegranate on NAFLD. PubMed, Scopus, and Google Scholar databases/search engines (from inception up to July 2023) were searched for interventional studies (human and animal) that examined the effects of supplementation with different parts of pomegranate including fruits, peels, seeds, or flower on NAFLD outcomes. A total of 222 articles were retrieved following the initial search. After excluding duplicates, the title and abstract of 114 articles were screened. Afterward, irrelevant articles were removed and the full texts of the remaining 27 articles were reviewed. Eventually, 19 articles (16 animal and three human interventional studies) that met the inclusion criteria, published between 2009 and 2023, were included in this systematic review. Our study indicates the potential beneficial effects of different parts of pomegranate on the improvement of NAFLD. However, given that the majority of the included articles were animal studies, further investigations in the form of human clinical trials are warranted to suggest a clinical indication of such interventions.

BACKGROUND: Pomegranate \'Punica granatum\' offers multiple health benefits, including managing hypertension, dyslipidemia, hyperglycemia, insulin resistance, and enhancing wound healing and infection resistance, thanks to its potent antioxidant and anti-inflammatory properties. It has been symbolized by life, health, femininity, fecundity, and spirituality.
OBJECTIVE: Although laboratory and animal studies have been conducted on the healing effects of pomegranate, there needs to be a comprehensive review on its anti-oxidative and anti-inflammatory effects in chronic disorders. We aim to provide a comprehensive review of these effects based on in-vitro, in-vivo, and clinical studies conducted in managing various disorders.
METHODS: A comprehensive search of in-vitro, in-vivo, and clinical findings of pomegranate and its derivatives focusing on the highly qualified original studies and systematic reviews are carried out in valid international web databases, including Web of Science, PubMed, Scopus, and Cochrane Library.
RESULTS: Relevant studies have demonstrated that pomegranate and its derivatives can modulate the expression and activity of several genes, enzymes, and receptors through influencing oxidative stress and inflammation pathways. Different parts of pomegranate; roots, bark, blossoms, fruits, and leaves contain various bioactive compounds, such as polyphenols, flavonoids, anthocyanins, and ellagitannins, that have preventive and therapeutic effects against many disorders such as cardiovascular diseases, diabetes, neurological diseases, and cancers without any serious adverse effects.
CONCLUSIONS: Most recent scientific evidence indicates that all parts of the pomegranate can be helpful in treating a wide range of chronic disorders due to its anti-oxidative and anti-inflammatory activities. Since the safety of pomegranate fruit, juice, and extracts is established, further investigations can be designed by targeting its active antioxidant and anti-inflammatory constituents to discover new drugs.

Pomegranate juice (PJ) has a possible anti-inflammatory effect because of its polyphenol content and antioxidants. However, the anti-inflammatory effect of PJ in randomized controlled trials (RCTs) has not been consistent. A previous meta-analysis conducted in 2016 reported a nonsignificant lowering effect of PJ on C-reactive protein (CRP) levels. This systematic review and meta-analysis aim to update the pooled effect size of PJ supplementation on CRP levels in RCT studies. PubMed, Scopus, and Web of Science databases were comprehensively searched until July 2023. Eligible studies were found by screening, their relevant data was extracted, and a risk of bias assessment was performed. The pooled effect size was calculated using a random effect model as the weighted mean difference (WMD) with a 95% confidence interval. This systematic review included 11 studies with 13 effect sizes and 696 participants. Meta-analysis showed that PJ supplementation led to a significant decrease in CRP levels compared to control groups (WMD: -2.55 mg/L; 95%CI: -3.44 to -1.66; p < 0.001). Subgroup analysis demonstrated the significant reduction effect of PJ on CRP levels in studies conducted on the both sexes or only females as well as Iranian population, individuals with 40 years≤, type 2 diabetes, polycystic ovary syndrome, or trials that intervened with PJ dosage of <250 ml/day. Meta-regression and dose-response analysis reported a nonsignificant linear and nonlinear relationship between intervention characteristics (duration and dose of PJ) and CRP changes. The current meta-analysis revealed that PJ supplemantation has a beneficial effect in improving CRP levels. It is recommended to understand this effect better, and find the optimal dose and duration of PJ supplementation to reduce CRP levels in the blood, and repeat meta-analysis after related RCTs are available. For the final proof of these effects, more detailed human studies are needed.

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.

Evidence supports the potential application of polyphenols as agents against obesity. Pomegranate is one of the fruits that possess a high content of polyphenols. This systematic review and meta-analysis of randomized controlled trials (RCTs) sought to evaluate the effects of pomegranate consumption on obesity indices, including body mass index (BMI), body weight, waist circumference (WC), fat mass (FM), body fat percentage (BFP), and fat-free mass (FFM) in adults. Relevant RCTs were obtained by searching databases, including PubMed, SCOPUS, and Web of Science, up to May 2023. Heterogeneity tests of the included trials were performed using the I 2 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. Pooled analysis of 28 trials revealed that pomegranate consumption led to a significant reduction in body weight (WMD: -1.97, 95% CI: -2.91, -1.03, p < .05), and a significant decrease in BMI (WMD: -0.48, 95% CI: -0.76, -0.20, p < .05) in comparison with the control group. However, there were no significant effects on WC, FM, FFM, and BFP in comparison with the control group. Pomegranate consumption may yield a beneficial effect on body weight and BMI in adults. However, there were no significant effects on WC, FM, FFM, and BFP, by pomegranate consumption. Also, pomegranate consumption can reduce body weight, BMI, WC, and BFP in obese adults. Long-term trials with different doses of pomegranate are needed.

OBJECTIVE: Epidemiologic studies have shown that type 2 diabetes (T2D) is more prevalent worldwide; therefore, improving glycemic indices to prevent or control T2D is vital. Randomized controlled trials (RCTs) on the effects of pomegranate consumption on glycemic indices have shown inconsistent results. Therefore, we aim to evaluate the impact of pomegranate consumption on fasting blood glucose (FBG), fasting insulin, hemoglobin A1c (HbA1c), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) in adults.
METHODS: A systematic literature search was performed using electronic databases, including PubMed, Web of Science, and Scopus, up to May 2023 to identify eligible RCTs evaluating the effect of pomegranate consumption on glycemic indices. 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 1999 records, 32 eligible RCTs were included in the current study. Our meta-analysis of the pooled findings showed that pomegranate consumption significantly reduced FBG (WMD: -2.22 mg/dL; 95 % CI: -3.95 to -0.50; p = 0.012), fasting insulin (WMD: -1.06 μU/ml; 95%CI: -1.79 to -0.33; p = 0.004), HbA1c (WMD: -0.22 %; 95% CI: -0.43 to -0.01; p = 0.037), and HOMA-IR (WMD: -0.30; 95%CI: -0.61 to -0.00; p = 0.046).
CONCLUSIONS: Overall, the results demonstrated that pomegranate consumption benefits glycemic indices in adults. However, further research with long-term interventions is required.
UNASSIGNED: CRD42023422780.

Neurodegenerative complications, like Alzheimer\'s disease (AD) exert adverse effects i.e. psychological and physiological in the central nervous system. The synthetic drugs used for these complications have negative effects on body health and therefore natural remedies are a good and targeted approach to counter such complications. Alternatively, fruits and a variety of biochemicals which are an important source of diet, can be used for remedial purposes. Due to the antioxidant properties of polyphenolic compounds, several companies utilize this property to advertise polyphenol-rich beverages. Pomegranate (Punica granatum L.), is one such fruit that is well known for its medical usage due to its antioxidant properties. In the cuurent study a literature search survey was performed on traditional uses, phytochemicals on pomegranate and their medical applications especaily in neurodegenerative deasese using electronic data bases like PubMed, Google Scholar, Scopus, Science Direct Wikipedia and Springer Nature. Based on previous preclinical and clinical studies, pomegranate juice, extracts, and its bioactive constituents have shown many mitigating properties, including suppression of inflammatory cell signaling, reduction in expression of genes associated with oxidative stress as well as pro-inflammatory cytokines in neurons, decreased production of inflammatory and oxidative stress biomarkers and increased expression of endothelial nitric oxide synthase. It also decreases the expression of soluble amyloid protein procurer β (sAPPβ), β-secretase and carboxyl terminal fragment β (CTFβ). Similarly, during an in-vivo study on APP/PS1 mice, pomegranate supplementation has been shown to impart cognitive aid by the protection of neurons and triggering neurogenesis through anti-inflammatory signaling pathway. In conclusion, pomegranate supplementation can be a promising source of protection against Alzheimer\'s disease.

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).
CONCLUSIONS: 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.

Pomegranate is widely used to preserve human health and help prevent many kinds of diseases. This study aims to review and assess the effects of pomegranate on women\'s health during and after menopause. PubMed, Web of science, Cochrane, Scopus, and Google Scholar were searched up to the end of 2022 with no language or study type restriction. All types of clinical research studies (randomized clinical trial [RCT], pre-post, case report, and case series) were included. The Cochrane RoB 2.0 tool was used for quality assessment of RCTs. A summary of intervention\'s effects for each study was provided by calculating standardized mean differences and accompanying 95% confidence interval using random effect model. Weighted mean differences and heterogeneity between studies were assessed using Hedges\'s method and Cochran\'s Q test, respectively. Pomegranate can significantly improve hot flashes severity and menopause symptoms and decrease FSH. It significantly improves high-density lipoprotein but not low-density lipoprotein, body mass index, and weight. Most of our results are inconclusive, and the small sample sizes and the lack of blinding and randomization have led to an increased risk of bias. Pomegranate can decrease menopause symptoms, but more well-designed studies, with bigger sample sizes are needed to establish its other clinical benefits for menopausal women.