Florina Andrica

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.

Tibolone Decreases Lipoprotein(a) levels in Postmenopausal Women: A Systematic Review and Meta-Analysis of 12 studies with 1009 patients

INTRODUCTION Circulating lipoprotein (a) (Lp(a)) is a recognized risk factor for cardiovascular disease (CVD). Tibolone, a synthetic steroid, may lower Lp(a) levels; however, evidence of the effects of tibolone on Lp(a) still remain to be defined. Therefore, we investigated the effects of tibolone treatment on circulating Lp(a) levels in postmenopausal women. METHODS The search included PUBMED, Web of Science, Scopus, and Google Scholar (up to January 31st, 2015) to identify controlled clinical studies investigating the effects of oral tibolone treatment on Lp(a) levels in postmenopausal women. Random-effects meta-regression was performed using unrestricted maximum likelihood method for the association between calculated weighted mean difference (WMD) and potential moderators. RESULTS Meta-analysis of data from 12 trials (16 treatment arms) suggested a significant reduction of Lp(a) levels following tibolone treatment (WMD: -25.28%, 95% confidence interval [CI]: -36.50, -14.06; p < 0.001). This result was robust in the sensitivity analysis and its significance was not influenced after omitting each of the included studies from the meta-analysis. When the studies were categorized according to the tibolone dose, there were consistent significant reductions of Lp(a) in the subsets of studies with doses <2.5 mg/day (WMD: -17.00%, 95%CI: -30.22, -3.77; p < 0.012) and 2.5 mg/day (WMD: -29.18%, 95%CI: -45.02, -13.33; p < 0.001). Likewise, there were similar reductions in the subsets of trials with follow-up either <24 months (WMD: -26.79%, 95%CI: -38.40, -15.17; p < 0.001) or ≥24 months (WMD: -23.10%, 95%CI: -40.17, -6.03; p = 0.008). CONCLUSIONS This meta-analysis shows that oral tibolone treatment significantly lowers circulating Lp(a) levels in postmenopausal women. Further studies are warranted to explore the mechanism of this effect and the potential value and place of tibolone or its analogues in the treatment of elevated Lp(a) in individuals at risk of CVD.

Effects of Quercetin on Blood Pressure: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Background Quercetin, the most abundant dietary flavonol, has antioxidant effects in cardiovascular disease, but the evidence regarding its effects on blood pressure (BP) has not been conclusive. We assessed the impact of quercetin on BP through a systematic review and meta‐analysis of available randomized controlled trials. Methods and Results We searched PUBMED, Cochrane Library, Scopus, and EMBASE up to January 31, 2015 to identify placebo‐controlled randomized controlled trials investigating the effect of quercetin on BP. Meta‐analysis was performed using either a fixed‐effects or random‐effect model according to I2 statistic. Effect size was expressed as weighted mean difference (WMD) and 95% CI. Overall, the impact of quercetin on BP was reported in 7 trials comprising 9 treatment arms (587 patients). The results of the meta‐analysis showed significant reductions both in systolic BP (WMD: −3.04 mm Hg, 95% CI: −5.75, −0.33, P=0.028) and diastolic BP (WMD: −2.63 mm Hg, 95% CI: −3.26, −2.01, P<0.001) following supplementation with quercetin. When the studies were categorized according to the quercetin dose, there was a significant systolic BP and diastolic BP‐reducing effect in randomized controlled trials with doses ≥500 mg/day (WMD: −4.45 mm Hg, 95% CI: −7.70, −1.21, P=0.007 and −2.98 mm Hg, 95% CI: −3.64, −2.31, P<0.001, respectively), and lack of a significant effect for doses <500 mg/day (WMD: −1.59 mm Hg, 95% CI: −4.44, 1.25, P=0.273 and −0.24 mm Hg, 95% CI: −2.00, 1.52, P=0.788, respectively), but indirect comparison tests failed to significant differences between doses. Conclusions The results of the meta‐analysis showed a statistically significant effect of quercetin supplementation in the reduction of BP, possibly limited to, or greater with dosages of >500 mg/day. Further studies are necessary to investigate the clinical relevance of these results and the possibility of quercetin application as an add‐on to antihypertensive therapy.

Effect of sour tea (Hibiscus sabdariffa L.) on arterial hypertension: A systematic review and meta-analysis of randomized controlled trials

Background: Hibiscus sabdariffa L. is a tropical wild plant rich in organic acids, polyphenols, anthocyanins, polysaccharides, and volatile constituents that are beneficial for the cardiovascular system. Hibiscus sabdariffa beverages are commonly consumed to treat arterial hypertension, yet the evidence from randomized controlled trials (RCTs) has not been fully conclusive. Therefore, we aimed to assess the potential antihypertensive effects of H. sabdariffa through systematic review of literature and meta-analysis of available RCTs. Methods: The search included PUBMED, Cochrane Library, Scopus, and EMBASE (up to July 2014) to identify RCTs investigating the efficacy of H. sabdariffa supplementation on SBP and DBP values. Two independent reviewers extracted data on the study characteristics, methods, and outcomes. Quantitative data synthesis and meta-regression were performed using a fixed-effect model, and sensitivity analysis using leave-one-out method. Five RCTs (comprising seven treatment arms) were selected for the meta-analysis. In total, 390 participants were randomized, of whom 225 were allocated to the H. sabdariffa supplementation group and 165 to the control group in the selected studies. Results: Fixed-effect meta-regression indicated a significant effect of H. sabdariffa supplementation in lowering both SBP (weighed mean difference −7.58 mmHg, 95% confidence interval −9.69 to −5.46, P < 0.00001) and DBP (weighed mean difference −3.53 mmHg, 95% confidence interval −5.16 to −1.89, P < 0.0001). These effects were inversely associated with baseline BP values, and were robust in sensitivity analyses. Conclusion: This meta-analysis of RCTs showed a significant effect of H. sabdariffa in lowering both SBP and DBP. Further well designed trials are necessary to validate these results.

Impact of L-carnitine on plasma lipoprotein(a) concentrations: A systematic review and meta-analysis of randomized controlled trials

We aimed to assess the impact of L-carnitine on plasma Lp(a) concentrations through systematic review and meta-analysis of available RCTs. The literature search included selected databases up to 31st January 2015. Meta-analysis was performed using fixed-effects or random-effect model according to I2 statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). The meta-analysis showed a significant reduction of Lp(a) levels following L-carnitine supplementation (WMD: −8.82 mg/dL, 95% CI: −10.09, −7.55, p < 0.001). When the studies were categorized according to the route of administration, a significant reduction in plasma Lp(a) concentration was observed with oral (WMD: −9.00 mg/dL, 95% CI: −10.29, −7.72, p < 0.001) but not intravenous L-carnitine (WMD: −2.91 mg/dL, 95% CI: −10.22, 4.41, p = 0.436). The results of the meta-regression analysis showed that the pooled estimate is independent of L-carnitine dose (slope: −0.30; 95% CI: −4.19, 3.59; p = 0.878) and duration of therapy (slope: 0.18; 95% CI: −0.22, 0.59; p = 0.374). In conclusion, the meta-analysis suggests a significant Lp(a) lowering by oral L-carnitine supplementation. Taking into account the limited number of available Lp(a)-targeted drugs, L-carnitine might be an effective alternative to effectively reduce Lp(a). Prospective outcome trials will be required to fully elucidate the clinical value and safety of oral L-carnitine supplementation.

Cardiotoxicity of anthracycline therapy: current perspectives

Anthracyclines, especially doxorubicin and daunorubicin, are the drugs of first choice in the treatment of patients with hematologic malignancies, soft-tissue sarcomas, and solid tumors. Unfortunately, the use of anthracyclines is limited by their dose-dependent and cumulative cardiotoxicity. The molecular mechanism responsible for anthracycline-induced cardiotoxicity remains poorly understood, although experimental and clinical studies have shown that oxidative stress plays the main role. Hence, antioxidant agents, especially dexrazoxane, and also other drug classes (statins, β-blockers) proved to have a beneficial effect in protecting against anthracycline-induced cardiotoxicity. According to previous clinical trials, the major high-risk factors for anthracycline-induced cardiotoxicity are age, body weight, female gender, radiotherapy, and other diseases such as Down syndrome, familial dilated cardiomyopathy, diabetes and hypertension. Consequently, further studies are needed to elucidate the molecular pathogenesis of anthracycline-induced cardiotoxicity and also to discover new cardioprotective agents against anthracycline-induced cardiotoxicity.

New Insights Regarding the Potential Health Benefits of Isoflavones

Isoflavones are a class of plant secondary metabolites, with an estrogen‐like structure presenting a plethora of biological activities. The chapter discusses important facts about this class of phytoestrogens, from biosynthesis to the latest research about their health benefits. The following major points discussed are: biosynthesis, regulation, isolation, metabolism and bioavailability, isoflavones in diet and intake, and new insights regarding the therapeutic effect including cancer chemoprevention. The chapter ends with a mini review of own research of the anti‐inflammatory and chemopreventive activity of iso‐ flavonoid genistein alone and incorporated in modern pharmaceutical formulations. The chapter updates the interested researchers in the field with the latest progress regarding potential health benefits of isoflavones.

Silver-, gold-, and iron-based metallic nanoparticles: Biomedical applications as theranostic agents for cancer

Abstract Neoplastic disease, displaying an increasing frequency worldwide, causes a dramatic decline of life quality due to adverse effects of classical chemotherapy. The main obstacles frequently encountered in antitumor therapy may be partially overcome through the use of nanoparticulate systems with targeted delivery that may act as therapeutic and/or diagnostic agents. Nanoparticles (NPs) are colloidal systems of submicron sizes, highly heterogenic, and which, following conjugation with biomolecular ligands, may be used to target malignant tumors with high affinity and specificity. Recently, metallic NPs have become a topic of interest in the scientific literature due to their physicochemical properties and intrinsic biological activity. The present chapter aims to provide a systematic search of the main biomedical applications, as theranostic agents for cancer, of three types of metallic NPs, based on silver, gold and iron/iron oxide, also offering an insight on future perspectives. The paper does not claim to offer comprehensive data in any area, but rather to emphasize the most recent advances in the antitumor use of metallic NPs. The chapter also includes several reviews focused on the same topic in order to highlight the new aspects herein introduced.

IMPACT OF L-CARNITINE ON PLASMA LIPOPROTEIN(A) CONCENTRATIONS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

We aimed to assess the impact of L-carnitine on plasma Lp(a) concentrations through a systematic review of literature and meta-analysis of available randomized controlled trials (RCTs). The literature search included PUBMED, Cochrane Library, Scopus, and EMBASE up to 31 January 2015 to identify

THE EFFECT OF QUERCETIN ON BLOOD PRESSURE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Quercetin, the most abundant dietary flavonol, has antioxidant effects in cardiovascular disease, but the evidences regarding its effects on blood pressure (BP) have not been fully conclusive. We assessed the impact of quercetin on BP levels through systematic review and meta-analysis of available