Current Pharmaceutical Biotechnology - Volume 17, Issue 7, 2016

The combination of genetic background together with food excess and lack of exercise has become the cornerstone of metabolic disorders associated to lifestyle. The scenario is furthermore reinforced by their interaction with other environmental factors (stress, sleeping patterns, education, culture, rural versus urban locations, and xenobiotics, among others) inducing epigenetic changes in the exposed individuals. The immediate consequence is the development of further alterations like obesity and metabolic syndrome, and other adverse health conditions (type-2 diabetes, cardiovascular diseases, cancer, reproductive, immune and neurological disorders). Thus, having in mind the impact of the metabolic syndrome on the worldwide public health, the present review affords the relative roles and the interrelationships of nature (genetic predisposition to metabolic syndrome) and nurture (lifestyle and environmental effects causing epigenetic changes), on the establishment of the metabolic disorders in women; disorders that may evolve to metabolic syndrome prior or during pregnancy and may be transmitted to their descendants.

Intra-uterine growth retardation (IUGR) represents one of the major problems in perinatal medicine. IUGR is one of main causes of perinatal mortality and morbidity. A huge number and variety of established and possible causes of IUGR have been described. There are currently no data about effective treatment of this fetal condition. IUGR has been described to be strictly involved in fetal programming. Fetal programming is the general idea, which tells us how during development of the embryo and fetus significant physiological parameters can be shaped by environmental events. A link between the intra-uterine growth retardation and the risk of developing type 2 diabetes, obesity and cardiovascular disease postnatally has been well documented. The aim of this paper is to present an overview of the current knowledge of IUGR effects on development of hypertension and cardiovascular diseases, impact on insulin secretion and resistance, diabetes mellitus and metabolic syndrome. The influence of intrauterine growth retardation on predisposition to obesity and adipose dysfunction was also described.

The number of pregnant women affected by gestational diabetes mellitus (GDM) is increasing among Caucasians, and East Asians. GDM also increases the risk for later advent of type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease in both women and their offspring. The underlying mechanism of GDM is not fully elucidated. Incretins such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), have been suggested to have a role in maternal metabolism and weight as well as fetal growth. These hormones might be implicated in mechanisms that compensate for the increment in glycemia and insulin resistance seen during pregnancy, while other factors, such as heredity, environment and lifestyle, but also different race/ethnic background might also lead to the comorbid health problems. Some studies indicate that pregnancy is associated with a diminished GLP-1 response which is more prominently evident in women with GDM and normalizes after delivery. Postprandial GIP level seems to be unaffected by pregnancy, despite its increased level in GDM. On the other hand, the reduced incretin effect observed in GDM may represent a risk factor for obesity, T2DM and metabolic disorders even in the offspring of these women. Further investigations are needed to establish the exact role of incretins in pregnancy and gestational glucose intolerance.

Gestational diabetes mellitus (GDM) is traditionally defined as hyperglycemia first detected in pregnancy. The risk of GDM is much higher among obese women than in their lean counterparts. An excess of adipose tissue leads to immune and inflammatory responses of both white adipose tissue and the placenta, contributing to systemic inflammation. Although the significance of both obesity and inflammation is relatively well characterized in GDM, the molecular mechanisms involved are not fully defined and require further study. In recent years huge progress has been made in identifying the intracellular signaling pathways involved in the pathophysiology of GDM. However, currently available data regarding inflammation and obesity in women with GDM are still conflicting or incomplete. We discuss selected aspects of the problem and propose future directions for research in the hope of achieving a better understanding of the disease. In particular, this review highlights recent studies exploring molecular alterations related to insulin resistance, inflammation of the adipose tissue and the placenta, lipotoxicity or endotoxemia.

Maternal nutrition and lifestyle before and during pregnancy influence both mother and offspring’s health and can be correlated with the metabolic syndrome in later life. Findings from animal and human studies indicate that nutrition during pregnancy has an important role in microbiological, metabolic, physiologic and immunologic development and homeostasis. A low nutritional intake in early pregnancy may represent a risk for adverse effects during pregnancy as well as on birth outcome. It seems that dietary supplementation with probiotics in perinatal period may represent safe and practical approach in dealing with the most common adverse pregnancy outcomes such as obesity and gestational diabetes. The SPRING (Study of Probiotics in the prevention of Gestational diabetes) will give important answers about potential benefits of probiotics in pregnant women who are obese and overweight and otherwise at the high risk for complications during pregnancy. Fish oil supplementation during the last trimester of pregnancy showed no effects on plasma lipids and lipoproteins in offspring, as well as on their adiposity. The effect of hypercholesterolemia during pregnancy on both mothers and child needs to be further investigated as it could have a biological role. The guidelines for the eventual clinical approach currently do not exist. Potential benefits of nutraceuticals on several metabolic parameters have been suggested. Limited evidence does not allow to draw final conclusions on preventive health strategies and dietary patterns that should be promoted during pregnancy. Further prospective and intervention studies are needed to establish it. Healthy lifestyle and dietary advice with appropriate supplements usage should be considered.

Pre-eclampsia appears to be the main cause for the maternal and fetal morbidity and mortality. Pregnant women with pre-eclampsia are more likely to be threatened with conditions which potentially may be lethal, such as: disseminated intravascular coagulation, cerebral hemorrhage, liver and renal failure. Pregnancy complicated with pre-eclampsia is also associated with a greater risk for iatrogenic prematurity, intrauterine growth retardation, premature abruption of placenta, and even intrauterine fetal death. In the majority of cases the reasons for arterial hypertension among pregnant women remain obscure. For the past decades, there were many abortive attempts in the use of some microelements, vitamins or specific diets, such as polyunsaturated fatty acids, for the prophylaxis of pre-eclampsia. Recently, it has been shown that a prevention of pre-eclampsia with the use of a lowmolecular- weight heparins (LMWHs) and acetylsalicylic acid (ASA) could considerably reduce the frequency of preeclampsia. In this review, we present the studies concerning the applications of LMWHs and aspirin in the prophylaxis of pre-eclampsia and some important data about the mechanisms of anti-inflammatory actions of LMWHs and ASA.

The study of natural substances has increased in recent years in the search for compounds with pharmacological properties that can be used for the development of new drugs. The alkaloids, substances extracted natural sources, show promising pharmacological activities, including pharmacological activities for the treatment of neurodegenerative diseases such as Alzheimer's disease, whose treatment is based on the use of various drugs. Thus, the article aims to a technological prospecting of alkaloids that presented important properties in the treatment of neurodegenerative diseases, namely, antioxidant, anxiolytic, anti-inflammatory and antidepressant properties. A literature review was conducted in the databases PubMed, Science Direct, Scopus, Scielo and Google Academics using the following key words: alkaloids, pharmacology, neurodegenerative diseases, cholinesterase inhibitors, antidepressants, anti-inflammatories, antioxidant and anxiolytic. Articles, dissertations and theses published between 2003 and 2015 were selected. Several studies showed through in vitro of in vitro and/or in vivo methods that many alkaloids extracted from plants showed anticholinesterase, antioxidant, anxiolytic, anti-inflammatory and antidepressant properties in the treatment of symptoms and progression of certain diseases such as Alzheimer's disease.

Brain glioma has become a great threat to human health in decades. To maximize the therapeutic efficacy of brain glioma as well as minimize the side effects, drugs should be penetrated through the blood brain barrier (BBB) and then targeted to the brain carcinoma cells with effective concentration. A dual-ligand delivery strategy was employed to achieve both of these goals. Herein, both specific targeting ligand transferrin and cell-penetrating peptide TAT were conjugated onto liposomes (TF/TAT-LP) to develop a brain glioma dual-ligand delivery system. Synergistic combination of doxorubicin (DOX) and paclitaxel (PTX), compared with using them separately, could more efficiently suppress tumor aggravation. In vitro studies including cellular uptake and three-dimensional (3D) tumor spheroid penetration assays proved that TF/TAT-LP could target brain endothelial and carcinoma cells with deeply penetration through the endothelial monolayers and target to the core of the tumor spheroids. In vivo imaging proved that the TF/TAT-LP possesses the highest tumor distribution, which was also confirmed by fluorescent images of the brain section. Ultimately, the DOX and PTX-loaded TF/TAT-LP (TF/TAT-PTX/DOX-LP) shows the best anti-glioma effect with improvement of glioma bearing survival time. In conclusion, synergistic combination of doxorubicin and paclitaxel delivered by the TF/TAT-LP could efficiently target to the brain glioma with satisfying treatment efficiency, which may be a promising formulation for glioma therapy.

This paper studies the phytochemical analysis of the acetone extracts of the Ramalina fraxinea and Ramalina fastigiata lichens and the antioxidant, antimicrobial and antitumour activities of these species and their constituents. The phytochemical analysis of two Ramalina species was evaluated using HPLC-UV test. The depsides (evernic acid, obtusatic acid, sekikaic acid and atranorin), depsidones (protocetraric acid) and dibenzofurane (usnic acid) were identified from these lichens. Antioxidant activity was evaluated by DPPH assay, reducing power assay and by measuring the amounts of total phenolics in extracts. Antimicrobial activity was tested towards five bacterial and 10 fungal species, using broth microdilution method to determine the minimum inhibitory concentration. Cytotoxic activity was tested using MTT method on the human epithelial carcinoma (Hela), human lung carcinoma (A549) and human colon carcinoma (LS174) cells. As a result of the study, tested samples showed strong free radical scavenging activity with IC50 values within the range of 285.45-423.51 μg/mL. Absorbance for reducing power was found to be from 0.0043 to 0.1747. The total amount of phenol concentrations in extracts of Ramalina fraxinea and Ramalina fastigiata was 32.63 and 33.49 μg PE/mg, respectively. Methyl evernate showed the strongest antimicrobial properties with the least measured MIC value being 0.125 mg/mL. In addition, all samples exhibited strong anticancer activities against tested cells (IC50 values were between 24.63 and 161.37 μg/mL). These results indicate that lichen appears to be a possible natural biopharmaceutical.