Current Drug Metabolism - Volume 18, Issue 1, 2017

Background: The investigation of the cellular components, their interactions and related functions constitute the major conditions in order to understand the cell as an integrated system. More specifically, the Protein-Protein Interactions and the obtained networks are very important in the majority of biological functions and processes, while most of the proteins appear to activate their functionalities through their interaction. Methods: Our in depth review analysis, include Sixty-five peer-reviewed research and review studies from several bibliographic databases. The most significant components were fully described, filtered, combined and analyzed in order to provide documented proofs on the Protein-Protein Interaction Network' applications in biomedicine. Results: The Protein-Protein Interaction Network' alignment and mapping give the opportunity of further knowledge extraction concerning the evolutionary relationships between the species through conserved pathways and protein complexes. Additionally, Protein-Protein Interaction Network information has been demonstrated to be able to predict functionally orthologous proteins within sequence homology clusters. Our review analysis concluded that, while Protein- Protein Interaction was used to be characterized just by their large and plain interacting surfaces, they were considered inapplicable for drug discovery studies for a long time. Conclusion: The present review explores multiple technologies implicated in Protein-Protein Interaction Networks, implicating their potential role in drug discovery mechanisms.

Background: Sponges are rich source of bioactive natural products synthesized by the symbiotic bacteria belonging to different phyla. Due to a competition for space and nutrients the marine bacteria associated with sponges could produce more antibiotic substances. To explore the proactive potential of marine microbes extensive research has been done. These bioactive metabolites have some unique properties that are pharmaceutically important. Methods: For this review, we have performed a non-systematic search of the available literature though various online search engines. This review provides an insight that how majority of active metabolites have been identified from marine invertebrates of which sponges predominate. Results: Sponges harbor abundant and diverse microorganisms, which are the sources of a range of marine bioactive metabolites. From sponges and their associated microorganisms, approximately 5,300 different natural compounds are known. Current research on sponge-microbe interaction and their active metabolites has become a focal point for many researchers. Various active metabolites derived from sponges are now known to be produced by their symbiotic microflora. Conclusion: In this review, we attempt to report the latest studies regarding capability of bacteria from sponges as producers of bioactive metabolite. Moreover, these sponge associated bacteria are an important source of different enzymes of industrial significance. In present review, we will address some novel approaches for discovering marine metabolites from bacteria that have the greatest potential to be used in clinical treatments.

In clinical studies, drugs with hydrophobic characteristic usually reflect low bioavailability, poor drug absorption, and inability to achieve the therapeutic concentration in blood. The production of poor solubility drugs, in abundance, by pharmaceutical industries calls for an urgent need to find the alternatives for resolving the above mentioned shortcomings. Poor water solubility drugs loaded with polymeric micelle seem to be the best alternative to enhance drugs solubility and bioavailability. Polymeric micelle, formed by self-assembled of amphiphilic block copolymers in aqueous environment, functioned as solubilizing agent for hydrophobic drug. This review discusses the fundamentals of polymeric micelle as drug carrier through representative literature, and demonstrates some applications in various clinical trials. The structure, characteristic, and formation of polymeric micelle have been discussed firstly. Next, this manuscript focuses on the potential of polymeric micelles as drug vehicle in oral, transdermal routes, and anti-cancer agent. Several results from previous studies have been reproduced in this review in order to prove the efficacy of the micelles in delivering hydrophobic drugs. Lastly, future strategies to broaden the application of polymeric micelles in pharmaceutical industries have been highlighted.

Background: Lung cancer is one of the most fatal chronic diseases in the field of respiratory medicine. The purpose of this paper is to address the side effects of conventional treatment strategies and to report the findings of till date drug nanocarriers researches performed for lung cancer therapy. This review also highlights the outstanding results of several researches employing pulmonary delivery system of nano-based drug formulations suitable for lung cancer. Objective: Summarizing the advances made in the field of nanotechnology-based lung cancer management. Methods: We systematically searched for research literature using a well-framed review question and presented data in the tabular forms for readers’ convenience. Results: Sixty-four papers were included in the review, the majority of which represent latest researches in the field of nanoparticle-based drug delivery for lung cancer therapy. Conventional treatment strategies for lung cancer lack specificity and are limited by undesirable toxicities in normal cells, as well as a high rate of recurrence. Intervention of nanotechnology has revolutionized the therapy of lung cancer upto a great extent by overcoming the current constraints in conventional therapies. Pulmonary delivery of nano-based drug formulations has resulted in potentially more effective and advanced lung cancer therapy. Conclusion: Several nanoscale drug delivery systems for lung cancer treatment are at present in clinical trials and some of them already exist in commercially available forms in the marketplace. However, although nanoscale drug carriers for lung cancer treatment have demonstrated stupendous therapeutic potential at both preclinical and clinical trials, but there are still many limitations to be solved.

Background: Menopause-derived estrogen deprivation and related endocrine factors are linked to some symptoms typical of middle-aged women, such as hot flashes, aches, joint pain, stiffness, depressed mood, bone degeneration, nutritional dysfunction, or difficulty to maintain body mass. Clinical approaches to these problems often involve hormone replacement therapy and other modalities of therapeutic intervention. However, the well-known side effects associated with other pharmacological alternatives have led physicians and patients to pursue new strategies to alleviate these symptoms. As a physiological state, the first recommended option is a natural and healthy therapy, alone or in combination with pharmacotherapy in severe cases. Among other natural alternatives, E-MHK-0103, a nutraceutical lipoprotein extracted from Mytilus galloprovincialis, was found to have beneficial properties. Methods: We reviewed numerous high-impact references to show the controversies over the current treatments used to alleviate menopausal symptoms, and presented the results obtained with E-MHK-0103 as a good natural alternative. Results: E-MHK-0103 showed positive effects on hot flashes, mood swings, joint pain and bone stability, associated with its glucosamine-related anti-inflammatory effect and its high content of vitamins, minerals, iron and other substances, such as selenium and vitamin E. A significant increase in serum growth hormone, mediated by the hepatic secretion of insulin growth factor-1, and a slight decrease in bone alkaline phosphatase, calcium and β-crosslaps concentrations contribute to its beneficial impact on bone turnover. E-MHK-0103 also showed a powerful antioxidant effect and an increase in iron stores, of particular importance in women with low basal ferritin levels. Conclusion: The findings of this review confirm the efficiency of natural therapies in menopause symptoms, and EMHK- 0103 as a healthy choice for inclusion into clinical practice.

Parkinson’s disease (PD) is characterized by neurodegeneration and a progressive functional impairment of the midbrain nigral dopaminergic neurons. The cause remains unknown; however, several pathological processes and central factors, such as protein aggregation, mitochondrial dysfunction, iron accumulation, neuroinflammation and oxidative stress, have been reported. The current treatment method primarily targets symptoms by using anti-Parkinson drugs such as levodopa, carbidopa, dopamine (DA) agonists, monoamine oxidase type B inhibitors and anticholinergics to replace DA. When drug therapy is not satisfactory, surgical treatments are recommended. Unfortunately, the existing conventional strategies that target PD are associated with numerous side effects and possess an economic burden. Therefore, novel therapeutic approaches that regulate the pathways leading to neuronal death and dysfunction are necessary. For many years, nature has provided the primary resource for the discovery of potential therapeutic agents. Remarkably, many natural products from medicinal plants, fruits and vegetables have been demonstrated to be efficacious anti-Parkinson agents. These products possess neuroprotective properties as a result of not only their wellrecognized anti-oxidative and anti-inflammatory activities but also their inhibitory roles regarding iron accumulation, protein misfolding and the maintenance of proteasomal degradation, as well as mitochondrial homeostasis. The aim of this review is to report the available anti-Parkinson agents based on natural products and delineate their therapeutic actions, which act on various pathways. Overall, this review emphasizes the types of natural products that are potential future resources in the treatment of PD as novel regimens or supplementary agents.

Cerebrovascular disease (CD) and metabolic syndrome (MetS) are two devastating health dilemma that continues to be a potential contributor to disability and mortality in human population all across the world. Scientific data clearly shows several mechanistic similarities between these two co-existing and interlinked conditions. The linkage exacerbates ongoing patho-physiological condition towards more lethal events. In view of the presence of modifiable risk factors in both CD and MetS, their management holds potential therapeutic value. Hence, developing common treatment strategies for these diseases could involve common molecular agents. In this communication, we have summarized some of the common pathological conditions viz. abdominal obesity, insulin resistance, dyslipidemia, hypertension, and endothelial dysfunction that further deteriorate existing homeostasis in CD and MetS. Based on our article, it is advocated that substantial improvements in novel multi-targeted drug discovery could provide the effective treatment methods in order to avoid the fatal complications related with CD and MetS.

Background: Antibiotic resistance is a global problem that presents significant risk to human health. Driven by selective pressure of antimicrobial agents, spontaneous mutation, recombination and horizontal gene transfer events, inappropriate antibiotic prescribing and use outside healthcare settings has increased their impact on healthcare system. Increasing risk for human health lead us to study resistance development mechanisms, associated factors that increase dissemination of resistance genes along with information of imperative measures necessary to curtail the growing menace. Methods: In this article, we emphasized on the state of knowledge regarding imprudent use of antibiotics that act as promoters of resistance development. For this, literature based search for articles and entries related to antimicrobial resistance was done. With ample of data available, selected was performed for the epidemiological and clinical based study to curtail the facts present in these data sets so as to get accurate and important information. Results: Resistance mediated by different determinants such as TEM, SHV, OXA and CTX-M, methods of mobilization that increase spread across species and as such failure to available treatment regimens was studied. Addition to detection methods, information of the inhibitors and natural substance useful in mitigating the effect of multidrug resistance was included to strategies the policies and plans for restricting their spread. Conclusion: As intervention to this growing problem, modified use of antimicrobial agents, employment of different formulations of herbs along with public health interventions in restricting antibiotic use, are believed to be of great help in restricting their dissemination and as such spread to non-pathogenic bacterial isolates.

Objective: The efficacy and safety of flibanserin in the treatment of Hypoactive Sexual Desire Disorder (HSDD) is controversial. We reviewed existing evidence on the efficacy and safety of flibanserin in treating HSDD, and performed a meta-analysis of reported effects. Method: Literature search was performed in PubMed, Scopus, and Cochrane library to find all trials on the efficacy of flibanserin in HSDD. Meta-analysis was performed using fixed- and random-effects models. Egger’s test and "trim and fill" methods were used for the assessment of publication bias and imputation of potentially missing studies, respectively. Results: Among 105 studies that were initially found, only ten related documents (six published and four nonpublished studies) were included in the final analysis, comprising 8345 subjects (6113 and 2232 subjects in the flibanserin and placebo groups, respectively). Incomplete outcome data bias was probable in the included studies. Most studies had an acceptable validity and quality. There was no significant difference between flibanserin and placebo groups in most of the HSDD-assessed indices. Our results showed that although SSE, DSDS, FSFID and FSFI are significantly improved with flibanserin, this change did not reach statistical significance compared with placebo. For FSDSR-item 13 score and FSDSR total score, no significant difference was observed between flibanserin and placebo. The most common side effect of flibanserin was somnolence. The most common causes of heterogeneity were black ethnicity, duration of therapy, age of participants and duration of marital relationship. Conclusion: the efficacy of flibanserin in women with HSDD was not found to be significantly different compared with placebo. Additional trials are required to clarify the efficacy of flibanserin for the treatment of HSDD.