Research in Pharmaceutical Sciences
Volume:8 Issue: 4, Nov 2013

Terbutaline sulfate exhibits extensive first pass metabolism and a short elimination half life which makes frequent oral administration of the drug inevitable. A novel buccoadhesive controlled delivery system of the drug can easily overcome the problem. A two-layered core tablet composed of a fast release layer made of mannitol, lactose, PEG and the drug attached to a sustained release layer composed of drug, varying ratios of HPMC, Carbomer 934 (CP), and lactose capped with a buccoadhesive cup coated with an impermeable backing layer was developed. Buccoadhesive cup initially optimized for bioadhesion strength using HPMC and CP with various ratios. Drug transport through buccal membrane indicated a high permeability coefficient (0.00105 cm/sec). All tablets were acceptable with regard to drug contents, thickness, weight variations, hardness and drug content uniformity. The CP:HPMC 2:1 mixture showed the best mucoadhesion properties and was selected as excipient for the cup layer. Swelling index was higher for formulations containing greater amount of lactose and lower percentage of polymers. Fast release layer released its entire content within 15 min while sustained release layer lasted for 12 h. Drug release controlled by a combination of diffusion and chain relaxation mechanism.

Tyrosinase is a multifunctional oxidase that is widely distributed in nature. It is a key enzyme in melanin biosynthesis and is involved in determining the color of mammalian skin and hair. In addition it is responsible for the undesirable enzymatic browning that occurs in plant-derived foods, limiting the shelf -life of fresh-cut products with the resultant economic loss. In recent years there has been considerable interest to study the inhibitory activity of tyrosinase and a number of inhibitory compounds derived from natural sources or partly/fully synthetic have been described. However, the current conventional methods to control tyrosinase action are inadequate. Considering the significant industrial and economic impact of the inhibitors of tyrosinase, this study was set to seek new potent inhibitors of this enzyme. A series of 3-hydroxypyridine-4-one derivatives were prepared in high yield and evaluated for their inhibitory activity on tyrosinase enzyme using dopachrome method. Our results show that all synthesized compounds have inhibitory effect on tyrosinase activity for the oxidation of L-DOPA. Among compounds studied those containing two free hydroxyl group (ie Va and V''a) were more potent than their analogues with one hydroxyl group (ie Vb and V''b). Also substitution of a methyl group on position N1 of the hydroxypyridinone ring seems to confer more inhibitory potency.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease of unknown etiology. Recent investigations have demonstrated that the impaired immune response is a common characteristic feature of IPF. Unfortunately, no definitive and effective drug treatment is available that could improve or at least inhibit the progressive course of this fatal disease. That is why one of the main priorities of pulmonary fibrosis investigations is to identify novel and effective molecular targets for preventive and therapeutic interventions. caffeic acid phenethyl ester (CAPE) is one of the most interesting bioactive compounds extracted from bee propolis. It has been shown that CAPE has an antioxidant activity and modulatory impact on immune system. Accordingly, the aim of the present study was to investigate the regulatory effects of CAPE on the levels of type I collagen (COL-1) and Interferon-gamma (IFN-γ) in bleomycin (BLM)-induced pulmonary fibrosis. Immunohistochemistry procedure was employed to assess the effects of CAPE on lung tissue. In this study, male Sprague-Dawley rats were divided into 5 groups (n=8) included 1: Positive control group: bleomycin (BLM). 2: Negative (saline) control group. 3, 4: Treatment groups of 1 and 2: BLM+CAPE (5 and 10 μmol/kg/day, respectively). (5: Sham group: CAPE (10 μmol/kg/day). BLM application resulted in significant changes in the level of studied parameters as compared to the controls. CAPE could decrease type I collagen concentration, modulate IFN-γ level, increase the animals’ body weight and decrease the lung index dose-dependently, compared with model group. In conclusion, CAPE may provide a novel therapeutic target for treating pulmonary fibrosis.

Swertia species are widespread in Eastern and Southern Asian countries and used in traditional medicine as anti-pyretic, analgesic, gastro and liver tonic. Among different species, only Swertia longifolia grows in Iran. In this investigation, antioxidant, cytotoxic and acetylcholinesterase inhibitory activities of S. longifolia have been studied. Aerial parts and roots of the plant were collected, dried and extracted with methanol 80% (total extract). Different extracts of the plant were obtained using hexane, chloroform, ethyl acetate, methanol, methanol:water (1:1) and water, respectively. Cytotoxic activity was determined by MTT assay on MDBK, HepG2, MCF7, HT29 and A549 cell lines. Antioxidant activity was measured by 2,2-diphenyl-1-picryl hydrazyl (DPPH) free radicals and acetylcholinesterase inhibitory (AChEI) effect was evaluated based on Ellman’s method in 96-well microplates.The results showed no cytotoxicity of the plant extracts on MDBK, HepG2, MCF7, HT29 and A549 cell lines up to 100 mg/ml. All samples showed radical scavenging activity but methanol extract of aerial parts and ethyl acetate extract of the roots showed the highest effects.Total extract of the roots showed higher AChEI activity than the aerial parts. Among different extracts, chloroform and ethyl acetate extracts of the roots and chloroform and methanol:water extracts of the aerial parts were more potent in AChEI assay. It is concluded that aerial parts and roots of the plant are rich in antioxidant agents with no cytotoxicity on selected cell lines up to 100 mg/ml. Moreover, since antioxidant and AChEI activity of compounds play an important role in the treatment of Alzheimer’s disorder, this plant might be a potential candidate for isolation of antioxidant and AChEI compounds which could be used as supportive treatment of Alzheimer’s disease.

Considering the emergence of antibiotic resistance, scientists are interested in using new antimicrobial agents in the treatment of infectious diseases including infections of the enteric systems. Lactic acid bacteria have the great potential to produce antimicrobial compounds that inhibit and control pathogenic bacteria. The aim of this study was to determine the anti-bacterial and anti-adherence properties of Lactobacillus delbrueckii subsp bulgaricus against Escherichia coli. The antibacterial activity of L. delbrueckii was investigated using disc diffusion and spot on lawn methods. In vitro anti-adhesion effect of L. delbrueckii against E. coli was examined using Caco-2 cells. In anti-adhesion assay, three competition conditions including competitive inhibition, adhesion inhibition, and displacement were examined. In spot on lawn method the zone of growth inhibition of E. coli by L. delbrueckii was 21.1 mm. The cell free supernatant of L. delbrueckii showed a good antibacterial activity against E. coli which was mainly related to lactic acid produced by L. delbrueckii. When two bacteria added simultaneously (competitive inhibition) degree of inhibition of E. coli binding by L. delbrueckii was 77%. In adhesion inhibition assay, L. delbrueckii was able to exclude E. coli adherence by around 43.5%. Displacement assay showed that L. delbrueckii had strong displacement ability toward E. coli and reduction of E. coli attachment by bound L. delbrueckii was 81.3%. The results suggest that L. delbrueckii may be able to inhibit E. coli infection in the gut; however more studies including in vivo studies need to be performed.

Herbal based remedies are used worldwide to treat psychiatric disorders. The aim of this study was to analyse the essential oil composition of Achillea Wilhemsii C. Koch (Asteraceae) and to evaluate its anxiolytic effects in the elevated plus maze (EPM) model of anxiety in rat. Gas chromatography/mass spectrometry (GC/MS) analysis of the essential oil showed that the main compounds of the oil were p-ocimen (23%), 1, 8-cineole (20.8%) and carvone (19.13%). The EPM results showed that 1 mg/kg (i.p.) of the oil significantly (P<0.05) increased the percentage of the time spent and the number of entries in the open arms of the maze while it did not change the total number of entries in the maze arms. These effects were not reversed with 2 mg/kg flumazenil and 5 mg/kg naloxone. We concluded that a minimum dose of 1 mg/kg of the oil has anxiolytic effects which are not probably mediated through GABA and opioid receptors.

Rosa damascena flower is widely used for gastrointestinal (GI) disorders. However, its pharmacological action on isolated ileum has not been studied. In this research, the effect of extract of flower petals of R. damascena Mill. growing in Kashan, Iran, on ileum motility was investigated. Hydroalcoholic extract was prepared by percolation method. A section of rat ileum was suspended in an organ bath containing Tyrode’s solution. The tissue was stimulated with electrical field stimulation (EFS), KCl and acetylcholine (ACh). The tissue was kept under 1g tension at 37°C and continuously gassed with O2. Effect of the R. damascena extract was studied on ileum contractions induced by EFS, KCl and ACh and compared with that of atropine. R. damascena extract (10-100 mg/ml) induced a contraction in rat isolated ileum while at 1mg bath concentration it had relaxant effect on rat ileum. Hydroalcoholic extract of R. damascena (1-8 mg/ml) concentration dependently inhibited ileum contraction induced by KCl (IC50=3.3 ± 0.9 mg/ml), ACh (IC50=1.4 ± 0.1 mg/ml) and EFS (IC50=1.5 ± 0.3 mg/ml). The vehicle had no significant effect on ileum contractions. From this experiment it was concluded that R. damascena extract at microgram concentrations had stimulatory effect on ileum smooth muscle. However, at milligram concentrations, it shows an inhibitory effect. This is most likely due to presence of different components in the extract. The stimulatory effect of the extract confirms its benefits for the treatment of constipation. Therefore, separation and identification of active components is recommended.

Accurate quantum chemical computations based on density functional theory (DFT) were performed on the series of 2-(4-(naphthalen-2-yl)-1,2,3-thiadiazol-5-ylthio)-N-acetamide (TTA) derivatives. The local reactivity of the acetamide derivatives as anti-HIV drugs were studied in terms of Fukui functions in the framework of DFT. The results based on the basis set superposition error (BSSE) corrections showed that the mechanism of bond formation between the acetamide derivatives and tyrosine as a biological molecule occurs mainly through nitrogen atoms. The intramolecular interaction energies between the acetamide derivatives and tyrosine were calculated and the nature of the intermolecular interaction was revealed by natural bond orbital charge (NBO) analysis. The results suggest that acetamide derivatives with bromophenyl and nitrophenyl substitutions are the most potent as anti-HIV drugs.

Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) developed as a selective inhibitor of cyclooxygenase-2 (COX-2) for the treatment of rheumatoid arthritis disease. Recently some other mechanisms have been identified for anti cancer activity of these agents including induction of apoptosis, inhibition of tumor vascularization, stimulation of antitumor immune responses and inhibition of cellular protein synthesis. The cytotoxic effects of four synthesisized analogues of celecoxib (coded as D, E, F and G) were evaluated against Hela, MDA-MB-231, A-2780-s and HT-29 cancer cells, using MTT assay; Also their induction of apoptosis using DNA fragmentation analysis were studied. MTT assay showed that cell survival percent of COX-2 positive cell lines (HT-29, MDA-MB-231 and Hela; p≤0.05) were decreased significantly after exposure to the tested COX-2 inhibitors while little effect was observed on the COX-2 negative cell line (A-2780-s). Results also showed that A-2780-s and Hela were the most resistant and the most sensitive cell lines to these compounds, respectively. Moreover, in DNA fragmentation assay, induction of apoptosis was confirmed by electrophoretic pattern of separated DNA fragments in Hela cell line. Compounds E and G in comparison with D and F exerted more cytotoxic effect on COX-2 positive cell lines (Hela, HT-29 and MDA-MB-231). This could be due to the hydrophobic substituent (Cl, CH3) located at the para position of phenyl ring leading to more lipophilicity and cell uptake. In addition, these COX-2 inhibitors induced apoptosis on Hela cell-line, which could be considered as one of the cytotoxic mechanisms of these compounds as potential anti cancer agents.