Pharmaceutical Sciences
Volume:26 Issue: 4, Dec 2020

One of the most known species of the genus Vaccinium (Ericaceae) is Vaccinium vitis-idaea L. or lingonberry. Leaves are included in the State Pharmacopoeia of the Russian Federation (XIV-th edition) and the State Pharmacopoeia of the Republic of Belarus (II-nd edition). The aim of this review is an analysis of data about a chemical content and types of pharmacological activities of Vaccinium vitis-idaea L. to discuss the tendency of future investigations on this plant. The main parts of works describe researches of chemical contents of fruits as medicinal and edible plant material. The majority of researches describe results of in vitro experiments. A significant interest is the study of the neuroprotective activity of the Vaccinium vitis-idaea extracts as well as their anti-cytokine and antiapoptotic properties and metabolic effects. The main biologically active compounds are phenologlycosides, tannins, proanthocyanes, saponins etc. These results will be of great significance for the development of new drugs from this plant and use along with the fruits of other parts of the plant.

Bortezomib (BTZ) as a specific proteasome inhibitor is used to inhibit proliferation and migration of tumor cell in variety of cancers. Targeted delivery of this drug not only would minimize its unwanted side effects but also might improve its efficacy. This purpose could be gotten through different pathways but using efficient carriers may be the best one without using any additional ingredients/ materials. Some polymer based nanoparticles with specific functional groups have the ability to interact with boronic acid moiety in BTZ. This reaction might play an important role not only in cancer targeting therapy but also in loading and release properties of this drug. Novel modification such as making multifunctional or pH-sensitive nanocarriers, may also improve anticancer effect of BTZ. This review might have remarkable effect on researchers’ consideration about other possible interactions between BTZ and polymeric nanocarriers that might have great effect on its remedy pathway. It has the ability to brought bright ideas to their minds for novel amendments about other drugs and delivery systems.

Euphorbia prostrata constitutes a herbal medication widely used to cure numerous inflammatory diseases occurring either alone or in conjunction with other herbal formulations. The research conducted was devised with the aim of determining the effect of Euphorbia prostrata hydroalcoholic leaf extract on paw swelling, joint destruction, and the formation of inflammation-producing cytokines in animal models of rheumatoid arthritis.

Hydroalcoholic Euphorbia prostrata extract and a reference drug (indomethacin 3mg/kg), were both administered orally on a daily basis at varying doses; low (50 mg/kg), medium (100 mg/kg), and high (200 mg/kg) for a period of 21 days. Other parameters affecting the functional components of bone include joint diameter measurements and histopathological investigations. Immunohistochemical analysis of Interleukin (IL-1, IL-6) and Nuclear Factor(NF-κB)in ankle joint tissue was performed.

The research findings indicated that a significant (p<0.05) dose-dependent reduction in inflammation results from the administering of Euphorbia prostrata at varying doses. A 200mg/kg dose of Euphorbia prostrata with a significance of p<0.001 produced a marked reduction in both inflammation and joint dysfunction. It was concluded, therefore, that such a dose attenuates paw oedema and inflammation, while also reversing bone damage through the inhibition of activated pro-inflammatory mediators and, specifically, NF-κB-mediated production of cytokines.

The research presented here concludes that Euphorbia prostrata hydroalcoholic extract can be potentially employed in the treatment and management of rheumatoid arthritis since it reduces symptoms of inflammation, inhibits macrophage activity and modulates IL-1, IL-6 and NF-κB.

As one of the major complications of diabetes, cardiovascular disease might result in early death in people with diabetes. miR-126 and 210 expressions undergo alterations in cardiac disease and cause heart failure.

Animals were divided into the 5 groups of control (Con), diabetes (Dia), diabeticcrocin (Dia-Cro), diabetic-voluntary exercise (Dia-Exe), and diabetic-crocin-voluntary exercise (Dia-Cro-Exe). Type 2 diabetes was induced by the use of a high-fat diet (4 weeks) and injection of streptozotocin (STZ) (i.p, 35 mg/kg). Animals received crocin orally (50 mg/kg), and voluntary exercise was performed alone or together for 8 weeks. QRT–PCR method was used to determine the levels of miR-210 and miR-126 in cardiac tissue.

The levels of miR-210 and miR-126 in the cardiac tissue augmented in both the crocin and voluntary exercise groups in comparison with the non-treated group (p<0.001). The use of combination therapy with exercise and crocin magnified their effects on miR-210 and miR-126 levels (p<0.001). Moreover, MiR-210 levels were lower in the crocin group compared to the exercise group (p<0.001).

The results indicated that voluntary exercise combined with crocin might provide a novel therapeutic plan for cardiovascular disease through increasing miR-210 and miR-126 expression.

Depression associated with aggression can lead to violent behaviors. The present study was aimed to determine how sertraline, a standard medication for depression treatment, can efficiently decrease aggression and affect psychophysiological parameters in patients with depression.

Patients with depression and aggression were included in a six-week trial with sertraline (50 100 mg/day). Depression diagnosis was confirmed by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, Text Revision (DSM-IV-TR). Depression severity before and after treatment was assessed using Beck Depression Inventory (BDI). Aggression was evaluated by Spielberger’s State-Trait Anger Expression Inventory-2 (STAXIII). The BDI and STAXI-II were finally applied to evaluate the effectiveness of treatment. For each patient, peripheral and central psychophysiological parameters were recorded using peripheral biofeedback apparatus and electroencephalogram in the initial and final stages of treatment. These recordings were attempted to assess variations of the autonomic nervous system and electrocortical activity in response to treatment.

Depressive and aggressive symptoms decreased significantly over the six-week treatment period, as measured by BDI and STAXI-II. Significant changes in some of the peripheral and central psychophysiological variables were observed. Sensorimotor rhythm (SMR)/theta ratio (p=0.01) have decreased during a task, delta (p=0.02) and theta (p=0.008) wave activity and theta/alpha ratio (p=0.01) have increased during task, and theta/beta ratio has increased during both rest and task (p=0.02 for both). Among peripheral psychophysiological variables, skin conductance during task decreased significantly (p=0.03).

Several numbers of psychophysiological parameters were influenced significantly after successful pharmacotherapy of aggressiveness in patients with depression.

Recombinant anti-vascular endothelial growth factor (VEGF) monoclonal antibodies and Fc-fusion proteins have been widely used for the effective treatment of retinal neovascular diseases. In this regard, VEGFR-Fc fusions, which act as strong VEGF inhibitors, have been approved for the treatment of age-related macular degeneration (AMD) and diabetic macular edema (DME). Production of monoclonal antibodies and Fc-fusion proteins relies on mammalian host systems such as Chinese hamster ovary (CHO) cells. Application of genomic regulatory elements including scaffold/matrix attachment regions (SAR/MARs) can profoundly affect recombinant protein expression in CHO cells.

To construct the VEGFR-Fc expression vectors, the enhanced green fluorescent protein (EGFP) gene was replaced by the VEGFR-Fc coding sequence in pEGFP-SAR-puro and pEGFP-puro vectors. Recombinant plasmids were transfected to CHO-K1 cells using TurboFect transfection reagent. VEGFR-Fc expression was evaluated in transiently transfected cells as well as stable cell pools and clones using an enzyme-linked immunosorbent assay (ELISA).

IFN-SAR showed no significant effect on transient expression of VEGFR-Fc during 72 h of culture. However, a 2.2-fold enhancement in VEGFR-Fc fusion protein titer was observed in IFN-SAR containing stable cell pools. Further evaluation of the VEGFR-Fc expression level in single-cell clones also indicated that clones with the highest VEGFR-Fc expression belonged to the pools transfected with IFN-SAR construct.

Our results indicate that the incorporation of IFN-SAR in expression vector can increase the expression of VEGFR-Fc in stable cell pools as well as single-cell clones. In contrast, transient expression of the fusion protein was not affected by IFN-SAR. More studies are needed to investigate the mechanism underlying this effect, including the analysis of mRNA expression and gene copy number in stable cell pools as well as clonal cells.

Active pharmaceutical ingredients face a challenge in manufacturing due to adverse physicomechanical properties. Desloratadine (DES) form I exhibits poor mechanical behavior through the formation of capping during the tableting process. Salt formation from DES and benzoic acid (BA) has been observed to resolve poor mechanical properties. However, the ability to withstand heat from the manufacturing process should be implemented in DES and DES-BA salt. The aim of this study was to determine the differences between thermal treatment results on DES and DES-BA salt and whether it causes them to undergo polymorphic transformation.

Salt was crystallized between DES and BA using the solvent evaporation method. DES and DES-BA salt were heated at 110°C, 159°C (melting point of DES), 181°C (melting point of DES-BA), and 190°C. Following this, characterization was performed using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and solubility testing.

Polymorphic transformation caused by heat occurred in DES, but not in DES-BA salt. The transformation of DES was induced by the effect of heating, which changed polymorph I to a mixture of polymorph I and III at 110°C, to polymorph II at 159°C, and to a mixture of polymorph I, II, and III at 190°C. Under 190oC, DES-BA is still stable and did not undergo a polymorphic transformation. However, at 190oC, decomposition started to occur, which implied decreased solubility, which did not occur in DES.

The heating process did not cause DES-BA salt to undergo a polymorphic transformation. However, it caused decomposition at 190oC. DES underwent a polymorphic transformation when exposed to the same condition without decomposition. This provided information to always pay attention to temperature during manufacturing processes that include DES or DES-BA salt to avoid physicochemical changes.

This study reports on the development of a controlled-release isoniazid (INH) drug delivery system using poly-є-caprolactone (PCL) functionalized magnetite-nanoparticles (MNPs), as a theoretical potential tool for tuberculosis (TB) chemotherapy.

The magnetite Fe3O4 core was fabricated by the co-precipitation method and coated with PCL by emulsion polymerization. INH was loaded onto the PCL-MNP surface to shape an INH-PCL-MNP nanocomposite. Deposing the INH on the nanocomposite surface was demonstrated through the molecular dynamics simulations. To investigate the stability of the polymer, the root-mean-square deviation (RMSD) and the radius of gyration (Rg) were calculated. The composite was characterized by Scanning electron microscopy (SEM) and X-Ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Mycobacterium tuberculosis was used to assess the antimicrobial activity of the nanoparticles. The drug loading efficiency, drug content, and in-vitro release behavior of the INH-PCL-MNPs were evaluated by UV–Vis spectrophotometry.

RMSD of PCL show that the structure of polymer after 40 ns is stable. INH molecules interested to spend more time close to the polymer. Rg of PCL indicated that PCL folded and radius of gyration changed near 1nm. The drug loading efficiency and drug content of the NPs were 720±46 mg/g and 69.3±3.8 (%), respectively. The compound showed a strong level of activity in-vitro. The amount of drug release at all times was above the minimum inhibitory concentration (MIC) (6 μg/ml).

INH-PCL-MNP nanocomposite have been effectively used as a potential tool to treat TB infections and a magnetic drug carrier system.

Repaglinide (REP) is an antihyperglycemic drug having low bioavailability due to its extensive first-pass metabolism. The present study aimed to develop and pharmacokinetic investigte the thiolated chitosan (TC) based buccal tablets of REP for improved bioavailability.

TC was prepared by conjugation of L-cysteine with chitosan. The amount of free thiol groups present in TC was determined by UV-spectrophotometry using Ellman’s reagent. TC based REP buccal tablets were prepared by two layers co-compression method and characterized for in vitro and ex vivo parameters. The in vivo performance of prepared REP buccal tablets was assessed by the pharmacokinetic study in New Zealand white rabbits.

The prepared TC resulted in 87%w/w yield with 52.3±3.2 μM free thiol functional groups per 10 mg of TC. The prepared formulations have good flow nature and compressibility, acceptable thickness (2.02 to 2.1 mm), weight (60.11 to 61.06 mg), surface pH (6.59 to 6.81) and drug content (98.92 to 101.08 %w/w). The presence of TC significantly improved the mucoadhesion strength, sustained the in vitro release and enhanced the ex vivo permeation of REP buccal tablets. The shelf life of REP buccal tablets was found to be 15.07 months in accelerated storage conditions. The prepared REP buccal tablets (V5) have area under the curve (712.22±15.91 ng/mL/h) and mean residence time (4.66±0.25 h) was 1.89 and 1.83 folds higher than oral bolus respectively.

TC based REP buccal tablets are capable of controlled transbuccal release of REP for a prolonged time and have better bioavailability than oral bolus.

Deep eutectic solvents (DESs) exist a wide variety of potential and existing applications. Based on the fact that the choline chloride (ChCl) is a complex B vitamin and widely used as food additive, the choline-based DESs are generically regarded as being harmless and non-toxic. In this regard, the low aqueous solubility of celecoxib (CLX) have been increased by use of DESs as neoteric class of solvents at T = (298.15 to 313.15) K.

DESs were prepared by combination of the ChCl/EG, U and G with the molar ratios: 1:2 and ChCl/MA with 1:1. The shake flask method was used to measure the solubility of CLX in the aqueous DESs solutions at different temperatures.

The solubility of the CLX increased with increasing the weight fraction of DESs. The observed solubility data was subjected to evaluate the relative performance of a number of models including Apelblat, Yalkowsky and Jouyban–Acree models for their correlation efficacy. Moreover, the apparent dissolution enthalpy, entropy and Gibbs free energy were obtained from the experimental solubility values.

It was found that the solubility data was satisfactorily fitted using the mentioned models at different temperatures. The dissolution process of CLX in the studied solvent mixtures within investigated temperature range was endothermic, and the driving mechanism is the positive entropy.

Application of natural-based herbal medicine is on a growing trend in some countries and people prefer to use plant-originated drugs rather than chemical-based ones. The present study describes an interesting sample preparation method for extraction and determination of cyproheptadine in herbal supplements as appetizing stimulant by using carbon nitride nanosheets as dispersive solid phase extraction method coupled with HPLCUV.

Various techniques used for characterization of adsorbent such as: Infrared spectroscopy (IR), scanning electron microscopy (SEM), Zeta potential analysis and powder X-ray diffraction (XRD). Optimization of the important extraction parameters were conducted by one parameter-at-a time method. Next, method validation was carried out.

The optimized cyproheptadine extraction parameters were introduced and under optimized conditions the method presented a good linearity in the concentration range of 300-2000 ng/g. The limit of detection (LOD) was 100 ng/g for the introduced method.

Quantitative analysis of fifteen real samples (Tablets or capsules) by proposed method confirmed the illegal presence of cyproheptadine in herbal appetizing stimulants supplements of the markets.

A bioassay-guided fractionation technique was used to evaluate the active constituents of the perennial plant L. officinale W.D.J. Koch (Apiaceae) against multidrug resistant (MDR) Mycobacterium tuberculosis.

Column chromatography was used to isolation of compounds from L. officinale and spectroscopic methods including 1D and 2D NMR (Nuclear magnetic resonance) and HRMS (high resolution mass spectrometry) were used to identification of the isolated compounds. Also, to evaluate antibacterial activity, minimum inhibitory concentration (MIC) was carried out by broth micro-dilution method. Finally, molecular docking (MD) was performed using the Schrödinger package to evaluate interactions between the active compounds and InhA protein.

Phytochemical analysis of the ethyl acetate extract of the plant roots led to isolation of bergapten (1), isogosferol (2), oxypeucedanin (3), oxypeucedanin hydrate (4), imperatorin (5), ferulic acid (6) and falcarindiol (7). Falcarindiol and oxypeucedanin indicated a moderate activity on MDR M. tuberculosis with MIC values of = 32 and 64 μg/mL, respectively. Antibacterial activity of falcarindiol was also observed against S. aureus and methicillin-resistant S. aureus strains with the MIC values of 7.8 and 15.6 μg/mL, respectively. The results of docking analysis showed a good affinity of oxypeucedanin (3) and falcarindiol (7) to InhA enzyme with docking score values of -7.764 and -7.703 kcal/mol, respectively.

Finally, 7 compounds were isolated from L. officinale that compounds 2-6 report for the first time from this plant. On the basis of the molecular docking (MD) study, oxypeucedanin (3) and falcarindiol (7) as active compounds against M. tuberculosis may be proposed as potential inhibitors of 2-trans-enoyl-ACP reductase (InhA), a key enzyme involved in the biosynthesis of the mycobacterial cell wall. Moreover, antibacterial activity of falcarindiol against methicillin-resistant S. aureus (MRSA) was remarkable.

Recent evidence presented the significant role of the microRNA-193 (miR-193) family in biological processes by the contribution of specific targeting, which mainly display as a tumor suppressor in various cancers. In the present study, we evaluated the effect of miR-193a-5p replacement on some metastasis gene expression in metastatic breast cancer (BC) cells.

For this purpose, firstly, the quantitative real-time polymerase chain reaction (qRTPCR) was used to detect the miR-193a-5p expression in the MDA-MB-231 BC cell line. Subsequently, miR-193a-5p was transfected into the cells, and the expression levels of ROCK1 (Rho‑associated, coiled‑coil containing protein kinase 1), CXCR4 (Chemokine Receptor-4), CD44, and vimentin genes were evaluated by qRT-PCR.

The expression level of miR-193a-5p strongly reduced in MDA-MB-231 cells. Interestingly, the ROCK1 (P < 0. 001), CD44 (P < 0.0001), CXCR4 (P < 0. 001) and vimentin (P < 0. 001) expression levels significantly decreased following miR-193a-5p transfection in MDA-MB-231 BC cells.

To conclude, it seems that miR-193a-5p restoration can attenuate the metastatic behavior of BC cells in vitro through decreased expression level of metastasis-related genes and may constitute an effective novel therapeutic strategy in miRNA-replacement therapy and treatment of metastatic breast adenocarcinoma in the future.