Current Pharmaceutical Biotechnology - Volume 20, Issue 3, 2019

Background: Globally, people utilize plants as the main source of remedy to heal various ailments. Medicinal plants have been utilized to treat ailments since the invention of modern scientific systems of medicine. The common remedy of infectious diseases mainly depends on the inhibition capacity of compounds or killing potential. The issue may give a clue for the development of a novel antimicrobial agent. Methods: Currently, microorganisms which are resistant towards antibiotics are probably a matter of serious concern for the overall well-being of health. At the moment, new therapeutic targets aside from the microorganism wall-based activities are in progress. For instance, the autoinducer molecules produced by the quorum sensing system are used to control antibiotic resistance and biofilm formation. Results: This therapeutic target is well-studied worldwide, however, the scientific data are not updated and only current studies started to gain insight into its perspective as a target to struggle against infectious diseases. Microbial resistance against antimicrobial compounds is a topic of serious concern in recent time. Conclusion: Hence, this paper aims to confer a current overview of the novel compounds, quorum sensing, quorum quenching, biofilm formation in the development of antibiotic resistance and an update on their importance as a potential target for natural substances.

Background: Liver ailments are among the leading causes of death; they originate from viral infections, chronic alcoholism, and autoimmune illnesses, which may chronically be precursors of cirrhosis; furthermore, metabolic syndrome may worsen those hepatopathies or cause Non-alcoholic Fatty Liver Disease (NAFLD) that may advance to non-alcoholic steatohepatitis (NASH). Cirrhosis is the late-stage liver disease and can proceed to hepatocellular carcinoma (HCC). Pharmacological treatment options for liver diseases, cirrhosis, and HCC, are limited, expensive, and not wholly effective. The use of medicinal herbs and functional foods is growing around the world as natural resources of bioactive compounds that would set the basis for the development of new drugs. Review and Conclusion: Plant and food-derived sterols and triterpenoids (TTP) possess antioxidant, metabolic-regulating, immunomodulatory, and anti-inflammatory activities, as well as they are recognized as anticancer agents, suggesting their application strongly as an alternative therapy in some chronic diseases. Thus, it is interesting to review current reports about them as hepatoprotective agents, but also because they structurally resemble cholesterol, sexual hormones, corticosteroids and bile acids due to the presence of the steroid nucleus, so they all can share pharmacological properties through activating nuclear and membrane receptors. Therefore, sterols and TTP appear as a feasible option for the prevention and treatment of chronic metabolic-related liver diseases, cirrhosis, and HCC.

Background: Herpes simplex virus (HSV) and poliovirus (PV) are both agents of major concern in the public health system. It has been shown that Dimorphandra gardneriana galactomannans can be used as solubilizer vehicles in the manufacturing of medicine. Mangiferin is the major constituent of Mangifera indica and presents multiple medicinal and biological activities. Objective: This study assayed the effect of D. gardneriana galactomannan combined with mangiferin (DgGmM) against HSV-1 and PV-1. Methods: The DgGmM cytotoxicity was evaluated by the colorimetric MTT method and the antiviral activity by plaque reduction assay, immunofluorescence and polymerase chain reaction (PCR), in HEp-2 cells. Results: The DgGmM showed a 50% cytotoxic concentration (CC50) > 2000 μg/mL. The 50% inhibitory concentrations (IC50) for HSV-1 and PV-1 were, respectively, 287.5 μg/mL and 206.2 μg/mL, with selectivity indexes (SI) > 6.95 for the former and > 9.69 for the latter. The DgGmM time-ofaddition protocol for HSV-1 showed a maximum inhibition at 500 μg/mL, when added concomitantly to infection and at the time 1 h post-infection (pi). While for PV-1, for the same protocol, the greatest inhibition, was also observed concomitantly to infection at 500 μg/mL and at the times 4 h and 8 h pi. The inhibition was also demonstrated by the decrease of fluorescent cells and/or the inhibition of specific viral genome. Conclusion: These results suggested that the DgGmM inhibited HSV-1 and PV-1 replication, with low cytotoxicity and high selectivity and, therefore, represents a potential candidate for further studies on the control of herpes and polio infections.

Background: Red ginseng is a traditional medicine that has been used to treat numerous metabolic and inflammatory diseases. Probiotic administration has been established to have beneficial effects in non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to determine whether a combination of Korean red ginseng (KRG) and probiotics could synergistically reduce NAFLD and liver inflammation compared with the effects reported for each individual product. Method: db/db and C57BL/6 mice were fed a normal chow diet and high-fat diet (HFD), respectively, and were treated with KRG, probiotics, or both. Samples were examined for lipid content, kinase protein phosphorylation, and gene expression patterns. Results: KRG- and probiotic-treated HFD-fed mice exhibited a reduction in body weight and a decrease in inflammatory cytokine secretion compared with the non-treated control mice. The same treatment was less successful in improving NAFLD parameters in the db/db mice while the combination of both products did not enhance their therapeutic potential. Conclusion: The results of this study indicate that KRG and probiotics administration ameliorated NAFLD symptoms in a mouse model of dyslipidemia by reducing weight gain and liver inflammation. Coadministration of both products did not enhance their efficacy, and further research should be conducted to clarify their mechanisms of action.

Background: The presence of subvisible particles (SVPs) in parenteral formulations of biologics is a major challenge in the development of therapeutic protein formulations. Distinction between proteinaceous and non-proteinaceous SVPs is vital in monitoring formulation stability. Methods: The current compendial method based on light obscuration (LO) has limitations in the analysis of translucent/low refractive index particles. A number of attempts have been made to develop an unambiguous method to characterize SVPs, albeit with limited success. Results: Herein, we describe a robust method that characterizes and distinguishes both potentially proteinaceous and non-proteinaceous SVPs in protein formulations using Microflow imaging (MFI) in conjunction with the MVAS software (MFI View Analysis Suite), developed by ProteinSimple. The method utilizes two Intensity parameters and a morphological filter that successfully distinguishes proteinaceous SVPs from non-proteinaceous SVPs and mixed aggregates. Conclusion: The MFI generated raw data of a protein sample is processed through Lumetics LINK software that applies an in-house developed filter to separate proteinaceous from the rest of the particulates.

Background: The modern immunology is targeted to the detailed study of various immunopathological conditions at the molecular and cellular level, development of new methods for the prevention, diagnostics and treatment of contagious and non-contagious diseases of humans and animals. Methods: In the present work we took the rats with model of cyclophosphamide-induced immunodeficiency and studied the features of gender impact of the complex extract of immunocompetent organs (thymus, spleen and mesenteric lymph nodes) Sus scrofa and its separate fraction with molecular weight less than 30 kDa administered to male and female rats. Results: The impact of gender differences and tissue-specific biomolecules (30 kDa fraction) on hematological parameters (leukocytes, erythrocytes, platelets), functional activity of immune system (IL-2, IL-4, IL-6, complement system, IgG, IgM), biochemical parameters of hepatocytes functioning (activity of ALP and LDG), carbohydrate metabolism (glucose) and lipid metabolism (triglycerides). Conclusion: Decrease of ALP activity is caused by inhibition of bile formation in a liver after introduction of cytostatic agent, and in contrast to complex extract, the administration of fraction 30 kDa allows improving bile production in male rats.

Background: Neuropilins (NRPs) participate in many processes related to cancer development such as angiogenesis, lymphangiogenesis and metastasis. Although endometrial cancer is one of the most common gynecological cancers, it has not been studied in terms of NRPs expression. Objective: The aim of this study was to investigate the potential utility of NRPs as important factors in the diagnosis and treatment of endometrial cancer. Methods: Our study consisted of 45 women diagnosed with endometrial cancer at the following degrees of histological differentiation: G1, 17; G2, 15; G3, 13 cases. The control group included 15 women without neoplastic changes. The immunohistochemical reactions were evaluated using light microscopy. Results: We did not detect the expression of NRP-1 and NRP-2 in the control group. NRP-1 expression was found exclusively in cancer cells. It was higher in G2 and G3 and reached about 190% of G1. NRP-2 expression was observed in the endothelium and was similar across all three cancer grades. In cancer cells, NRP-2 expression increased with the degree of histological differentiation. Conclusion: NRP1 and NRP2 are candidates for complementary diagnostic molecular markers and promising new targets for molecular, personalized anticancer therapies.

Background: Drug combination is a new therapy to improve antibiotic deficiency treatment towards biofilm resistance. Objective: This study was conducted to determine the potential effect of sodium oleate to inhibit established biofilms of two strains, methylotrophic bacteria Methylophilus quaylei in combination with ampicillin. Minimum inhibitory concentration (MIC) of ampicillin was determined and added in combination with sodium oleate and examined on planktonic and established biofilms of two strains M. quaylei were characterized by different properties of cell surface hydrophobicity. Methods: The effect on biofilms was evaluated by the number of colony forming units (CFUs), crystal violet assay, light and scanning electron microscopy. Results: The study demonstrates that sodium oleate has a promoting activity against planktonic growth of M. quaylei strains and has a slight inhibitory effect on biofilm. Addition of sodium oleate enhances the bactericidal effect of ampicillin against biofilm cells. Combination of ampicillin 0.1 mg/ml (MIC) and sodium oleate 0.03 mg/ml showed a remarkable destruction effect on established biofilms. Discussion: Combination of ampicillin 0.1 mg/ml (MIC) and sodium oleate 0.03 mg/ml showed a remarkable destruction effect on established biofilms. Overall, results indicated that sodium oleate in combination with ampicillin enhances the inhibition of M. quaylei biofilms and this combination can be utilized for combating bacterial biofilm resistance. Conclusion: Overall, results indicated that sodium oleate in combination with ampicillin enhances the inhibition of M. quaylei biofilms and this combination can be utilized for combating bacterial biofilm resistance.