Curcumin Therapeutic Modulation of the Wnt Signaling Pathway.

Curcumin, isolated from the rhizome of Curcuma longa, is one of the most extensively studied phytochemicals. This natural compound has a variety of pharmacological effects including antioxidant, anti-inflammatory, anti-tumor, cardio-protective, hepato-protective and anti-diabetic. Wnt signaling pathway, one of the potential targets of curcumin through upregulation and/or downregulation, plays a significant role in many diseases, even in embryogenesis and development of various organs and systems. In order to exert an anti-tumor activity in the organism, curcumin seems to inhibit the Wnt pathway. The downstream mediators of Wnt signaling pathway such as c-Myc and cyclin D1 are also modified by curcumin. This review demonstrates how curcumin influences the Wnt signaling pathway and is beneficial for the treatment of neurological disorders (Alzheimer's and Parkinson's diseases), cancers (melanoma, lung cancer, breast cancer, colon cancer, endothelial carcinoma, gastric carcinoma and hepatocellular carcinoma) and other diseases, such as diabetes mellitus or bone disorders.

The impact of argan oil on plasma lipids in humans: Systematic review and meta-analysis of randomized controlled trials.

The study aims to investigate the effect of argan oil on plasma lipid concentrations through a systematic review of the literature and a meta-analysis of available randomized controlled trials. Randomized controlled trials that investigated the impact of at least 2 weeks of supplementation with argan oil on plasma/serum concentrations of at least 1 of the main lipid parameters were eligible for inclusion. Effect size was expressed as the weighted mean difference (WMD) and 95% confidence interval (95% CI). Meta-analysis of data from 5 eligible trials with 292 participants showed a significant reduction in plasma concentrations of total cholesterol (WMD: -16.85 mg/dl, 95% CI [-25.10, -8.60], p < .001), low-density lipoprotein cholesterol (WMD: -11.67 mg/dl, 95% CI [-17.32, -6.01], p < .001), and triglycerides (WMD: -13.69 mg/dl, 95% CI [-25.80, -1.58], p = .027) after supplementation with argan oil compared with control treatment, and plasma concentrations of high-density lipoprotein cholesterol (WMD: 4.14 mg/dl, 95% CI [0.86, 7.41], p = .013) were found to be increased. Argan oil supplementation reduces total cholesterol, low-density lipoprotein cholesterol, and triglycerides and increases high-density lipoprotein cholesterol levels. Additionally, larger clinical trials are needed to assess the impact of argan oil supplementation on other indices of cardiometabolic risk and on the risk of cardiovascular outcomes.

The effects of cinnamon supplementation on blood lipid concentrations: A systematic review and meta-analysis.

BACKGROUND: Cinnamon is a rich botanical source of polyphenols, whose positive effects on blood lipid concentrations have been hypothesized, but have not been conclusively studied. OBJECTIVE: The objective of the study was to systematically review and evaluate the effect of administration of cinnamon on blood lipid concentrations. METHODS: We assessed 13 randomized controlled trials with 750 participants investigating the effect of cinnamon supplementation on blood lipid concentrations. A meta-analysis was performed using random effect models, with weighted mean differences (WMDs; with 95% confidence interval [CI]) for endpoints calculated using a random effects model. RESULTS: No statistically significant effect of cinnamon was observed on blood low-density lipoprotein cholesterol (LDL-C; WMD: -0.16 mmol/L [-6.19 mg/dL], 95% CI: -0.35, 0.03 [-13.53, 1.16], P = .10) and high-density lipoprotein cholesterol (HDL-C; WMD: 0.05 mmol/L [1.92 mg/dL], 95% CI: -0.03, 0.12 [-0.03, 4.64], P = .21) concentrations. However, a statistically significant reduction in blood triglycerides (WMD: -0.27 mmol/L [-23.91 mg/dL], 95% CI: -0.39, -0.14 [-34.54, -12.40], P < .01) and total cholesterol concentrations (WMD: -0.36 mmol/L [-13.92 mg/dL], 95% CI: -0.63, -0.09 [-24.36, -3.48], P < .01) was observed. HDL-C was significantly elevated after the omission of 1 study (WMD: 0.04 mmol/L [1.54 mg/dL], 95% CI: 0.03, 0.06 [1.16, 2.32], P < .01) during our sensitivity analysis. A meta-regression analysis was conducted, and no significant association was found between changes in lipid parameters and cinnamon dose. In contrast, changes in blood levels of total cholesterol (slope: 0.09; 95% CI: 0.02, 0.16; P < .01), LDL-C (slope: 0.05; 95% CI: 0.001, 0.10; P = .05) and triglycerides (slope: 0.06; 95% CI: 0.04, 0.09; P < .01) were significantly and positively associated with the duration of supplementation. No statistically significant association was found between blood HDL-C changes and duration of supplementation. CONCLUSION: Cinnamon supplementation significantly reduced blood triglycerides and total cholesterol concentrations without any significant effect on LDL-C and HDL-C.

Effects of tibolone on fibrinogen and antithrombin III: A systematic review and meta-analysis of controlled trials.

Tibolone is a synthetic steroid with estrogenic, androgenic and progestogenic activity, but the evidence regarding its effects on fibrinogen and antithrombin III (ATIII) has not been conclusive. We assessed the impact of tibolone on fibrinogen and ATIII through a systematic review and meta-analysis of available randomized controlled trials (RCTs). The search included PUBMED, Web of Science, Scopus, and Google Scholar (up to January 31st, 2016) to identify controlled clinical studies investigating the effects of oral tibolone treatment on fibrinogen and ATIII. Overall, the impact of tibolone on plasma fibrinogen concentrations was reported in 10 trials comprising 11 treatment arms. Meta-analysis did not suggest a significant reduction of fibrinogen levels following treatment with tibolone (WMD: -5.38%, 95% CI: -11.92, +1.16, p=0.107). This result was robust in the sensitivity analysis and not influenced after omitting each of the included studies from meta-analysis. When the studies were categorized according to the duration of treatment, there was no effect in the subsets of trials lasting either <12months (WMD: -7.64%, 95% CI: -16.58, +1.29, p=0.094) or ≥12months (WMD: -0.62%, 95% CI: -8.40, +7.17, p=0.876). With regard to ATIII, there was no change following treatment with tibolone (WMD: +0.74%, 95% CI: -1.44, +2.93, p=0.505) and this effect was robust in sensitivity analysis. There was no differential effect of tibolone on plasma ATIII concentrations in trials with either <12months (WMD: +2.26%, 95% CI: -3.14, +7.66, p=0.411) or≥12months (WMD: +0.06%, 95% CI: -1.16, +1.28, p=0.926) duration. Consistent with the results of subgroup analysis, meta-regression did not suggest any significant association between the changes in plasma concentrations of fibrinogen (slope: +0.40; 95% CI: -0.39, +1.19; p=0.317) and ATIII (slope: -0.17; 95% CI: -0.54, +0.20; p=0.374) with duration of treatment. In conclusion, meta-analysis did not suggest a significant reduction of fibrinogen and ATIII levels following treatment with tibolone.

The effect of statins on cardiovascular outcomes by smoking status: A systematic review and meta-analysis of randomized controlled trials.

Smoking is an important risk factor for cardiovascular disease (CVD) morbidity and mortality. The impact of statin therapy on CVD risk by smoking status has not been fully investigated. Therefore we assessed the impact of statin therapy on CVD outcomes by smoking status through a systematic review of the literature and meta-analysis of available randomized controlled trials (RCTs). The literature search included EMBASE, ProQuest, CINAHL and PUBMED databases to 30 January 2016 to identify RCTs that investigated the effect of statin therapy on cumulative incidence of major CVD endpoints (e.g. non-fatal myocardial infarction, revascularization, unstable angina, and stroke). Relative risks (RR) ratios were calculated from the number of events in different treatment groups for both smokers and non-smokers. Finally 11 trials with 89,604 individuals were included. The number of smokers and non-smokers in the statin groups of the analyzed studies was 8826 and 36,090, respectively. The RR for major CV events was 0.73 (95% confidence interval [CI]: 0.67-0.81; p<0.001) in nonsmokers and 0.72 (95%CI: 0.64-0.81; p<0.001) in smokers. Moderate to high heterogeneity was observed both in non-smokers (I2=77.1%, p<0.001) and in smokers (I2=51.6%, p=0.024) groups. Smokers seemed to benefit slightly more from statins than non-smokers according to the number needed to treat (NNT) analysis (23.5 vs 26.8) based on RRs applied to the control event rates. The number of avoided events per 1000 individuals was 42.5 (95%CI: 28.9-54.6) in smokers and 37.3 (95%CI: 27.2-46.4) in non-smokers. In conclusion, this meta-analysis suggests that the effect of statins on CVD is similar for smokers and non-smokers, but in terms of NNTs and number of avoided events, smokers seem to benefit more although non-significantly.

The Effects of Tamoxifen on Plasma Lipoprotein(a) Concentrations: Systematic Review and Meta-Analysis.

INTRODUCTION: Tamoxifen is a selective estrogen receptor modulator widely used in the treatment of breast cancer. Tamoxifen therapy is associated with lower circulating low-density lipoprotein cholesterol and increased triglycerides, but its effects on other lipids are less well studied. AIMS: We aimed to investigate the effect of tamoxifen on circulating concentrations of lipoprotein(a) [Lp(a)] through a meta-analysis of available randomized controlled trials (RCTs) and observational studies. METHODS: This study was registered in the PROSPERO database (CRD42016036890). Scopus, MEDLINE and EMBASE were searched from inception until 22 March 2016 to identify studies investigating the effect of tamoxifen on Lp(a) values in humans. Meta-analysis was performed using an inverse variance-weighted, random-effects model with standardized mean difference (SMD) as the effect size estimate. RESULTS: Meta-analysis of five studies with 215 participants suggested a statistically significant reduction of Lp(a) levels following tamoxifen treatment (SMD -0.41, 95% confidence interval -0.68 to -0.14, p = 0.003). This effect was robust in the sensitivity analysis. CONCLUSIONS: Meta-analysis suggested a statistically significant reduction of Lp(a) levels following tamoxifen treatment. Further well-designed trials are required to validate these results.

Lipid-modifying effects of krill oil in humans: systematic review and meta-analysis of randomized controlled trials.

Context: Some experimental and clinical trials have shown that krill oil, extracted from small red crustaceans, might be an effective lipid-modifying agent, but the evidence is not conclusive. Objective: The effect of krill oil supplements on plasma lipid concentrations was assessed through a systematic review of the literature and a meta-analysis of available randomized controlled trials. Data sources: PubMed and Scopus were searched up to March 25, 2016, to identify RCTs investigating the effect of krill oil supplements on plasma lipids. Study selection: Randomized controlled trials that investigated the impact of at least 2 weeks of supplementation with krill oil on plasma/serum concentrations of at least one of the main lipid parameters (ie, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglycerides) and that reported sufficient information on plasma/serum lipid levels at baseline and at the end of study in both krill oil and control groups were eligible for inclusion. Data extraction: Two reviewers independently extracted the following data: first author's name, year of publication, study location, study design, number of participants in the krill oil and control groups, dosage of krill oil, type of control allocation, treatment duration, demographic characteristics of study participants, and baseline and follow-up plasma concentrations of lipids. Effect size was expressed as the weighted mean difference (WMD) and 95% confidence interval (95%CI). Results: Meta-analysis of data from 7 eligible trials (14 treatment arms) with 662 participants showed a significant reduction in plasma concentrations of low-density lipoprotein cholesterol (WMD, -15.52 mg/dL; 95%CI, -28.43 to -2.61; P = 0.018) and triglycerides (WMD, -14.03 mg/dL; 95%CI, -21.38 to -6.67; P < 0.001) following supplementation with krill oil. A significant elevation in plasma concentrations of high-density lipoprotein cholesterol was also observed (WMD, 6.65 mg/dL; 95%CI, 2.30 to 10.99; P = 0.003), while a reduction in plasma concentrations of total cholesterol did not reach statistical significance (WMD, -7.50 mg/dL; 95%CI, -17.94 to 2.93; P = 0.159). Conclusion: Krill oil supplementation can reduce low-density lipoprotein cholesterol and triglycerides. Additional clinical studies with more participants are needed to assess the impact of krill oil supplementation on other indices of cardiometabolic risk and on the risk of cardiovascular outcomes.

The potential role of mitochondrial ATP synthase inhibitory factor 1 (IF1) in coronary heart disease: a literature review.

Cardiovascular disease (CVD) is the leading cause of death worldwide, and so the search for innovative and accurate biomarkers for guiding prevention, diagnosis, and treatment is a valuable clinical and economic endeavor. Due to a recent findings that the serum concentration of mitochondrial ATP synthase inhibitory factor 1 (IF1) is an independent prognostic factor in patients with coronary heart disease (CHD), we reviewed the role of this protein in myocardial ischemic preconditioning, its correlation to plasma high density lipoprotein (HDL), the predictive potential in patients with CHD, and its interplay with angiogenesis. IF1 has been positively correlated with plasma HDL-cholesterol, and is independently negatively associated with all-cause and CV mortality in patients with CHD. However, this conclusion is prevalently based on limited data, and more research is needed to draw definitive conclusions. IF1 seems to play an additional role in increasing cell vulnerability in oncologic diseases but may also function as modest inhibitor of angiogenesis in physiological conditions. It has been also explored that IF1 may rather act as a modulator of other molecules more significantly involved in angiogenesis, especially apolipoprotein A1 on which the largest effect could be observed. In conclusion, more research is needed to characterize the role of IF1 in patients with CHD.

Effects of pentoxifylline on inflammatory markers and blood pressure: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Pentoxifylline is a xanthine derivative with potential cardiovascular benefits. AIM: To evaluate the impact of pentoxifylline on blood pressure (BP) and plasma TNF-α, C-reactive protein (CRP) and IL-6 through a systematic review and meta-analysis of randomized controlled trials. METHODS: The protocol was registered (PROSPERO: CRD42016035988). The search included PUBMED, ProQuest, Scopus and EMBASE until 1 September 2015 to identify trials reporting BP or inflammatory markers during pentoxifylline therapy. Quantitative data synthesis was performed using a random-effects model, with weighted mean difference (WDF) and 95% confidence intervals (CIs) as summary statistics. RESULTS: Fifteen studies (16 treatment arms) were found to be eligible for inclusion. Meta-analysis did not suggest any effect of pentoxifylline on either SBP or DBP. Pentoxifylline treatment was associated with a significant reduction in plasma concentrations of TNF-α (WDF: -1.03 pg/ml, 95% CI: -1.54, -0.51; P < 0.001, 11 treatment arms) and CRP (WDF: -1.39 mg/l, 95% CI: -2.68, -0.10; P = 0.034, five treatment arms). No alteration in plasma IL-6 concentration was observed. The impact of pentoxifylline on plasma TNF-α levels was found to be positively associated with treatment duration (slope: 0.031; 95% CI: 0.004, 0.057; P = 0.023) but independent of pentoxifylline dose (slope: -0.0003; 95% CI: -0.002, 0.001; P = 0.687). CONCLUSION: Pentoxifylline did not alter BP or plasma IL-6 concentration, but significantly reduced circulating TNF-α and CRP concentrations.

Effects of supplementation with pomegranate juice on plasma C-reactive protein concentrations: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Pomegranate juice (PJ) has a high content of antioxidants and bioactive polyphenols, being widely used for its antioxidant, anti-inflammatory and chemopreventive effects. PURPOSE: The objective of this meta-analysis consisted in investigating the impact of PJ on plasma C-reactive protein (CRP) concentrations. METHODS: The search included SCOPUS, Medline and two Iranian bibliographic databases namely MagIran and Scientific Information Database (from inception to December 09, 2014) to identify prospective trials for investigating the impact of pomegranate preparations on serum concentrations of CRP. Two independent reviewers extracted data on study characteristics, methods and outcomes. RESULTS: Among 427 participants in the selected studies, 216 were allocated to PJ groups, and 211 to control group. Meta-analysis of data from 5 eligible randomized controlled trials (RCTs) arms did not provide compelling evidence as to a significant CRP-lowering effect of supplementation with pomegranate juice (WMD: -0.22 mg/l, 95% CI: -0.45, 0.01, p = 0.061). The impact of pomegranate juice on plasma CRP levels was found to be independent of duration of supplementation (slope: 0.003; 95% CI: -0.005, 0.011; p = 0.444). CONCLUSION: In conclusion, this meta-analysis of data from 5 prospective trials did not indicate a significant effect of PJ on plasma CRP levels, and this effect was independent of duration of supplementation.

Polyphenols-rich natural products for treatment of diabetes.

Currently, experimental and clinical evidences showed that polyphenols-rich natural products, like nutraceuticals and food supplements, may offer unique treatment modalities in type 2 diabetes mellitus (DM), due to their biological properties. Natural products modulate the carbohydrate metabolism by various mechanisms, such as restoring beta-cells integrity and physiology, enhancing insulin releasing activity, and the glucose using. Sea buckthorn berries, red grapes, bilberries, chokeberries and popular drinks like cocoa, coffee and green tea are all rich in polyphenols and may decrease the insulin response, offer in g a natural alternative of treatment in diabetes. Therefore, researches are now focused on potential efficacies of different types of polyphenols, including flavonoids, phenolic acids, lignans, anthocyans and stilbenes. Animal and human studies showed that polyphenols modulate carbohydrate and lipid metabolism, decrease glycemia and insulin resistance, increase lipid metabolism and optimize oxidative stress and inflammatory processes. It is important to understand the proper dose and duration of supplementation with polyphenols-rich extracts in order to guide effective therapeutic interventions in diabetic patients.