A new labdane diterpenoid, in vitro and in silico cytotoxicity, and protease inhibitory effects of phytochemicals from Juniperus polycarposK. Koch leaves.

Cytotoxicity-guided purification of Juniperus polycarpos K. Koch leaves (Cupressaceae) led to the isolation of a new labdane diterpenoid, 3-(acetyloxy)-acetylisocupressic acid (1), together with isocupressic acid (2), 3,4-dimethoxycinnamoyl alcohol (3) and deoxypodophyllotoxin (4). The chemical structures of 1-4 were established by detailed 1D and 2D NMR, HRFAB-MS and LRESI-MS, as well as by comparing the spectral data with those reported in the literature. Compound 1 was ineffective against HepG2 cells and protease enzyme, while 2 showed potent cytotoxicity against HepG2 cells (IC50 of 3.73 µg/mL) compared to cisplatin (IC50 of 12.65 µg/mL). Computational analyses with CDK1 protein (a prominent protein in the cell cycle of HepG2 cells) revealed the binding affinity of 2 (-31.86 kcal/mol) was better than 1 (-19.70 kcal/mol) because the acetoxy groups did not allow binding deeply to the ATP binding site. Compounds 2 and 4 moderately inhibited the protease activity (IC50 = 52.7 and 63.0 µg/mL, respectively). Further in vitro and in vivo studies on the plant are strongly recommended.

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.

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

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.

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

BACKGROUND AND AIM: 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). CONCLUSION: Overall, the results demonstrated that pomegranate consumption benefits glycemic indices in adults. However, further research with long-term interventions is required. PROSPERO REGISTRATION CODE: CRD42023422780.

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.

Allium hooshidaryae (Alliaceae); Chemical compositions, biological and ethnomedicine uses.

ETHNOPHARMACOLOGICAL RELEVANCE: Allium hooshidaryae (sect. Pseudoprason) is a wild plant in northwestern Iran. The plant is traditionally used, besides as spice, also for its medicinal properties. AIM OF THE STUDY: Due to the shortcoming evidence in scientific research and the importance of this plant in folk medicine, this study aims to assess the chemical compositions and biological activities, which have no longer reported to date. MATERIALS AND METHODS: The bulbs of A. hooshidaryae were collected from West Azerbaijan, Iran. The plant essential oil was obtained by hydrodistillation using Clevenger-type apparatus according to the European pharmacopeia. The plant hydromethanolic extract was obtained using maceration method. The volatile oil compositions of A. hooshidaryae bulbs were evaluated by use of combined gas chromatography/flame ionization detector (GC/FID) and gas chromatography/mass spectrometry (GC/MS) techniques. Furthermore, different biological activities of the yielded essential oil and hydromethanolic extract were in vitro evaluated. The antibacterial and antifungal activities were assessed using disc diffusion assay, tube dilution assay, minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), and minimal fungicidal concentration (MFC). The cytotoxic activities were assayed by reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) toward two human cancerous cell lines (MOLT-4 and MCF-7). Antioxidant activity was investigated using 2,2-diphenyl-1-picrylhydrazyl (DPPH•) radical scavenging assay. RESULTS: GC/FID and GC/MS analyses allowed detecting 62 components in the A. hooshidaryae essential oil representing the 91.87% of the total oil. The volatile compounds were identified by comparison of the relative retention indices (RRI), mass spectra with those in NIST08/NIH and Wiley (257 and 7 L) libraries and co-elution with authentic samples where available. Surprisingly, the most abundant compound was obtained as menthol (19.0%) followed by carvacrol (10.1%), menthone (6.4%), methyl (methylthiomethyl) disulfide (4.2%), dimethyl disulfide (3.8%), and thymol (3.8%). Contrary to the other Allium species enriched by sulfur compounds, just three compounds accounting for 10.7% of the total oil were obtained as the sulfur-sulfur bond containing components (Dimethyl disulfide, Methyl (methylthio) methyl disulfide, Bis-methylthiomethyl disulfide). The hydromethanolic extract of A. hooshidaryae showed higher anti-radical (IC50DPPH of 9.81 µg/mL) and cytotoxic (for MOLT-4 and MCF-7, IC50s were 76.3 and 128.6 µg/mL, respectively) activities rather than that of the obtained essential oil (IC50 DPPH of 39.9 µg/mL; IC50 MOLT-4 of 109.2 µg/mL, and IC50 MCF-7 of 297.5 µg/mL). While, the essential oil exhibited the anti-Staphylococcus aurous and anti-Escherichia coli activities approximately the same as Chloramphenicol (positive control). The MIC values were 31.25 and 62.5 µg/mL and the disk inhibition zone values were 23 and 21 mm, respectively. In addition, Candida albicans had moderate sensitivity (MFC of 62.5 µg/mL) for the essential oil. CONCLUSIONS: The hydromethanolic extract of A. hooshidaryae shows the potency to be used for food protection in addition to further cytotoxic investigations. Associated with antimicrobial abilities of both A. hooshidaryae products, the compatible results was observed with the traditional claim having being not investigated to date. These findings will facilitate the development of A. hooshidaryae for further deep investigations.

In vivo anti-inflammatory properties of aerial parts of Nasturtium officinale.

CONTEXT: Nasturtium officinale R. Br. (watercress) has long been used in Iranian folk medicine to treat hypertension, hyperglycemia, and renal colic. Moreover, anticancer, antioxidant, and hepatoprotective properties of N. officinale have been reported. OBJECTIVE: In this study, anti-inflammatory activity of the hydro-alcoholic extract from aerial parts of N. officinale was investigated. MATERIALS AND METHODS: Oral administration of the hydro-alcoholic extract of N. officinale (250, 500 and 750 mg kg(-1)) was investigated on two well-characterized animal models of inflammation, including carrageenan- or formalin-induced paw edema in rats. Then, the topical anti-inflammatory effect of N. officinale (2 and 5 mg/ear) was studied on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema. Finally, biopsy of the paw or ear was performed for pathological evaluation. RESULTS: Acute toxicity tests of N. officinale in rats established an oral LD50 of >5 g kg(-1). The extract of watercress (250, 500 and 750 mg kg(-1)) significantly inhibited carrageenan-induced paw edema 1, 2, 3 and 4 h after carrageenan challenge (p < 0.001). The extract (500 mg kg(-1)) also showed considerable activity against formalin-evoked paw edema over a period of 24 h (p < 0.001). Furthermore, topical application of N. officinale (5 mg/ear) reduced TPA-induced ear edema (p < 0.05). Histopathologically, the extract decreased swelling and the tissue damage induced by carrageenan or TPA. DISCUSSION AND CONCLUSION: Our findings indicate potent anti-inflammatory activity of N. officinale in systemic and topical application and propose its potential as an anti-inflammatory agent for treatment of inflammatory conditions.