Sci. Pharm., Volume 76, Issue 4 (December 2008) – 17 articles , Pages 567-798

In contrast to the huge variety of sesquiterpene lactones reported, only a limited number of flavonoids and phenolic acids are known from the genus Crepis. Compounds detected in the course of this investigation encompass flavonoids luteolin, luteolin 7-O-glucoside, luteolin 7-O-gentiobioside, luteolin 7-O-glucuronide, and luteolin 4’-O-glucoside and caffeic acid derivatives chlorogenic acid, 3,5-dicaffeoylquinic acid, caffeoyltartaric acid, and cichoric acid. The spectrum of compounds found in the flowering heads of plants of the genus Crepis are useful chemosystematic markers both to differentiate between species and to characterize the genus and help delimiting it from morphologically similar genera within the Cichorieae tribe of the Asteraceae family. Full article

This study presents the actions of risperidone (Risp) and haloperidol (Hal) on the behavioral effects elicited by ketamine (Ket) on open-field (OF), rota rod (RR) and tail suspension (TS) tests in mice. Male Swiss albino mice (25–30g) were used. Antipsychotics were administered alone (Risp: 0.1 or 0.2 mg/kg, ip; Hal: 0.1 and 0.2 mg/kg, ip) or thirty minutes before Ket (10 mg/Kg, ip). Ket increased (Ket: 63.3 ± 4.2) the locomotor activity compared to control, while neuroleptics decreased it (25.5 ± 4.2). Pretreatment with neuroleptics, in both doses, blocked hyperlocomotion caused by Ket. In RR, Ket decreased (Ket: 15 ± 4.1) the permanence time of the animals compared to control (Control: 59 ± 0.6), but this effect was not observed when neuroleptics were administered alone. Pretreatment with neuroleptics reverted the effect of Ket only in the RR. While Ket (17.3 ± 5.6) decreased the time of immobility in the tail suspension test compared to the control (80.2 ± 10.2), the pretreatment with neuroleptics reverted this mobility. The action of neuroleptics in this model made possible the blockade of the effects caused by acute administration of Ket. Thus, the mechanism of action of ketamine may involve the dopaminergic system. Full article

The blood-brain barrier (BBB) is a formidable obstacle for the delivery of therapeutic agents into the central nervous system. Hydroxysafflor yellow A (HSYA) has been shown to be effective in protecting cerebral ischemia. However, whether HSYA could cross the BBB has not been elucidated. In this work, the effect of cerebral ischemia/reperfusion injury on the BBB penetration for HSYA was investigated in normal, sham-operated and cerebral ischemia/reperfusion rats. The concentration of HSYA in homogenate of brain tissue was determined by reversed phase high performance liquid chromatography and the protein was assayed by Bradford assay. The results showed lower concentration of HSYA could be detected in normal rats at 10 to 60 min after HSYA administration. The HSYA concentration in ischemic hemisphere significantly increased, while there is no change in non-ischemic hemisphere. These results suggest that HSYA can penetrate the BBB with weak ability in physiologic condition, but cerebral ischemia/reperfusion injury increases HSYA penetration across BBB markedly.
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The purpose of present study was to prepare and characterize the complex between curcumin and soya lecithin, and to evaluate its hepatoprotective activity. The curcumin-soya lecithin complex was prepared by dissolving curcumin and soya lecithin in equimolar ratio in dichloromethane and heating at 60°C for 2 h. The curcumin-soya lecithin complex was characterized by DSC, FTIR and NMR spectroscopy. The prepared complex provided a 3-fold increase in solubility of curcumin. On evaluation of in vitro intestinal permeability of curcumin across the everted sheep gut sac, the complex was found to provide the higher intestinal permeation of curcumin. On in vivo evaluation of curcumin-soya lecithin complex in paracetamol-induced hepatotoxicity in mice, it was observed that the complexed curcumin afforded a significantly higher protection against paracetamol-induced rise in serum aspartate aminotransferase and alanine aminotransferase levels as compared to pure curcumin. Full article

Cilostazol is a potent phosphodiesterase inhibitor; its major effects are prevention of platelet aggregation and dilation of blood vessels via an increase in tissue cAMP levels. This study examined the effect of cilostazol on serum cAMP, type 1 plasminogen activator inhibitor and transforming growth factor-β1 in relation to alleviating cardiovascular complications. This was achieved in rats through administration of L-NAME (0.1 mg/ml) for two weeks, and then followed by i.p. single dose of streptozotocin (65mg/kg). Rats were classified to three groups; normal rats, control diabetic hypertensive rats and the third group was treated with cilostazol (1.8 mg daily, orally) for six weeks. Cilostazol improved serum cAMP level and increased plasma NO concentration leading to dilation of blood vessels. In addition, cilostazol has beneficial lipoprotein-modifying effect. Cilostazol treatment confirmed the positive correlation between plasma PAI-1 activity and serum TGF-β1 which is beneficial in reducing the hazards of cardiovascular complications. Thus, cilostazol therapy provides a broad spectrum of effects in alleviating cardiovascular complications induced in experimental animals. Full article

Objective: In this study, the effects of baicalin – a flavonoid purified from Scutellaria baicalensis. Georgi, Scutellaria L. – on alveolar bone resorption in rat experimental periodontitis were examined. Method: 12 Sprague-Dawley rats (SD rats) were randomly divided into four groups: Group A1, A2, B and C. Except for Group C – the control group–, Group A1, A2 and B were used to establish the rat periodontitis model by repeat injection of Lipopolysaccharide (LPS). At the same time, Group A1 and A2 were injected with baicalin of different concentration. 9 days later, the maxillae were extracted and analyzed using micro computerized tomography (micro-CT), followed by histological analysis. Result: Micro-CT images showed that alveolar bone resorption was severely induced around the molar by repeat injection of LPS. Treatment with high-dose baicalin (1.0 μg / ml) clearly recovered alveolar bone resorption, meanwhile, low-dose baicalin(0.1 μg / ml) showed a similar but weaker effect. Histological examination clarified that the number of osteoclast was dose dependently decreased by baicalin treatment. Conclusion: These findings suggest that baicalin may inhibit the alveolar bone loss in periodontitis effectively. Full article

This double blind randomised trial compared the clinical efficacy of Femineral^®, a proprietary herbal preparation containing highly soluble iron compounds, minerals, and vitamins, with Floradix^®, the most popular iron supplement in Scandinavia for patients with iron deficiency anaemia (IDA).
Fifty women of childbearing age and adolescent girls, all diagnosed with IDA, were randomised into two groups. One group (n = 26) was treated with Femineral (10 ml twice a day; 15 mg of iron supplement/day), while the second (n = 24) received Floradix^® (10 ml twice a day; 20 mg of iron supplement/day). The efficacy of 28 days of treatment in each group was evaluated by analysis of serum iron levels, blood haemoglobin and erythrocyte counts; by the mental performance of the patients on days one and 28; and by assessment of IDA symptoms, such as pale skin colour, fatigue, irritability, weakness, constipation, brittle nails, cold hands and feet, headache, blue tinge to sclera, and feeling of well being on days one, seven, 14 and 28.
The Femineral group showed significant improvements in blood haemoglobin levels and red cell counts after 28 days, while the Floradix group did not. The Femineral group showed better improvements in other IDA symptoms, such as impaired mental performance, pale skin colour, fatigue, irritability, weakness, constipation, brittle nails, cold hands and feet. Both groups showed significant improvements in serum iron levels at the end of the study. Such improvements correlate with the results of memory tests: the number of errors by both groups was significantly lower at the end of the study. There were no significant differences in memory tests between the two groups. Eight patients in the Floradix group and one in the Femineral group reported drowsiness. The Femineral group reported two other adverse events (nausea and vomiting). Femineral can be used safely in the treatment of iron deficiency anaemia. It is more efficient and safe than Floradix. Full article

Chemokines receptors have emerged as important drug targets for development of agents against the HIV/AIDS pandemic. With the purpose of designing new chemical entities with enhanced antagonistic potencies against the CCR5 chemokine receptor, the QSAR study carried out on 70 novel phenoxybenzyl derivatives as antagonists of CCR5 HIV co receptor is presented. The developed model was validated by standard QSAR parameters and through a detailed structural analysis on how it reproduces the quantitative differences observed in the experimentally known activity data. The model showed a good correlative and predictive ability having a cross validated correlation co-efficient (r²_cv) of 0.708 and a conventional correlation coefficient (r²) was found to be 0.805. The study revealed that the CCR5 antagonistic activity exhibited by the series is largely explained by steric factors of substituents emphasizing the role of size and shape of the inhibitors in making effective antagonist-CCR5 binding chemistry. A detailed investigation was made on the structural basis for the antiretroviral activity and the insights gleaned from the study could be usefully employed to design antagonists with a much more enhanced potency and selectivity. Full article

The cyclodextrins have a wide range of applications in different areas of drug delivery and pharmaceutical industry due to their complexation ability and other versatile characteristics. The most common pharmaceutical application of cyclodextrin is to enhance the solubility, stability, safety and bioavailability of drug molecules. The purpose of this review is to discuss and summarize some of the findings and applications of cyclodextrin (CD) and their derivatives in different areas of drug delivery. This article highlights the molecular structure, properties like complexation, solubility etc. of cyclodextrins and focuses on its use for parenteral, oral, ophthalmic and nasal drug delivery. Other routes including dermal, rectal, sublingual and pulmonary delivery are also briefly addressed. The objective of this contribution is to focus on the potential use of chemically modified cyclodextrins as high-performance drug carriers in drug delivery systems with emphasis on the more recent developments. Thus cyclodextrins, because of their continuing ability to find several novel applications in drug delivery, are expected to solve many problems associated with the delivery of different novel drugs through different delivery routes. Full article

The aim of this work was the chemical modification of pectins by limited acetylation of their free hydroxyl groups to yield high ester pectins and to investigate its swelling and erosion behavior along with the effect on the release pattern of drugs. Ibuprofen as a weakly acidic drug was formulated as tablets using chemically modified pectin and its impact on drug release was studied. Optimum concentrations of the modified pectin in such a system protect the tablet throughout the gastrointestinal tract (GIT) for 10–12 hrs. The pectin modified with acetylating agent was found to be promising to modify the release of drugs which are to be delivered throughout GIT. Drug dissolution studies were carried out in buffers of pH 1.2 and 6.8 and the system was designed based on the total GIT transit time concept. This article reviews physicochemical characterization of chemically modified pectins, correlation of the physicochemical characteristics with the drug release pattern of ibuprofen and the potential use of chemically modified pectin for modified release dosage forms. Full article

A new high-throughput liquid chromatographic tandem mass spectrometric (LC-MS/MS) assay for the quantification of valproic acid in human plasma was developed and validated. The separation was performed on a Zorbax SB-C18 column under isocratic conditions using a 48:52 (v/v) mixture of acetonitrile and 0.1% (v/v) acetic acid in water at 45 °C with a flow rate of 0.8 mL/min. The detection of valproic acid was performed in SIM mode (m/z 143.1). The human plasma samples (0.2 mL) were deproteinized with methanol and aliquots of 2 μL from supernatants obtained after centrifugation were directly injected into the chromatographic system. The method shows a good linearity (r > 0.9972), precision (CV > 7.8 %) and accuracy (bias > 5.7 %) over the range of 5-200 μg/mL plasma. Lower limit of quantification (LLOQ) was 5 μg/mL and the recovery was between 98-106 %. The method is not expensive, it needs a minimum time for plasma sample preparation and has a run-time of 2.4 min for instrument analysis (retention time of valproic acid was 1.8 min). The developed and validated high-throughput method is very simple, rapid and efficient, with wide applications in clinical level monitoring, pharmacokinetics and bioequivalence studies. Full article

Two unknown impurities were detected in stressed samples (by hydrochloric acid and hydrogen peroxide) of paroxetine hydrochloride hemihydrate (an active pharmaceutical ingredient – API) using a gradient reversed-phase high performance liquid chromatography (HPLC). These impurities were enriched and were present up to 30% in the degraded sample. The impurities were isolated from the degraded sample by column purification. Spectral data of the isolated impurities were collected. Based on the spectral data of two dimensional nuclear magnetic spectroscopy (2D-NMR) and mass spectrometry (MS) Impurity-1 and Impurity-2 were characterized as (3S,4R)-3-{[(6-chloro-1,3-benzodioxol-5-yl)oxy]methyl}-4-(4-fluorophenyl)piperidine and [(3S,4R)-4-(4-fluorophenyl)piperidin-3-yl]methanol respectively. Full article

The efficacy of polyion-complexes between charged liposomes and oppositely charged polymers for the oral delivery of therapeutic peptides and proteins has been reported previously. It was the aim of the current study, to investigate whether polyion-complexes between negatively charged liposomes and the cationic polymer poly(allylamine) (PALAM) can be formed. Furthermore, the protease inhibitory effect of PALAM, the drug-loading capacity of liposomal PALAM polyion-complexes as well as the toxicity of PALAM and liposomal PALAM polyion-complexes was evaluated. After mixing the negatively charged liposomes with a PALAM solution, the zeta-potential switched from a negative to a positive value, indicating the formation of the polyion-complexes. PALAM was capable of significantly inhibiting Trypsin, although this effect was not very pronounced. Drug-loading capacity using the hydrophilic marker fluorescein isothiocyanate-dextran (FD4) was determined to be 8.0 ± 1.5 %. Cytotoxicity tests using Caco-2 cells and MTS assay revealed that both, PALAM in solution as well as liposomal polyion-complexes displayed cell toxicity. Data gained within this study is believed to contribute to the development of PALAM based colloidal drug delivery systems. Full article

[⁶¹Cu]-N-(2-hydroxyacetophenone)glycinate ([⁶¹Cu]NHAG) was prepared using in house-made NHAG ligand and [⁶¹Cu]CuCl2 produced via the ^natZn(p,x)⁶¹Cu (180μA proton irradiation, 22MeV, 3.2h) and purified by a ion chromatography method. [⁶¹Cu]NHAG radiochemical purity was >98% and >99.9% by RTLC and HPLC methods respectively after purification by SPE. [⁶¹Cu]NHAG was administered into normal and tumor bearing mice followed by biodistribution studies up to 180 minutes. The best tumor accumulation was observed by animal sacrification after 120 min (tumor/muscle and tumor/blood ratios were 25.6 and 3.4 respectively). [⁶¹Cu]NHAG is a potential PET radiotracer for tumor imaging. Full article

A series of N-methyl/acetyl 5-(un)-substituted isatin-3-semicarbazones were screened for anticonvulsant and sedative-hypnotic activities. The results revealed that protection was obtained in all the screens i.e., Maximal electroshock, (MES) subcutaneous pentylene tetrazole (scPTZ) and subcutaneous strychnine (scSTY) screens. Three compounds (2a,2e and 2i) possessed anti-MES activity and all the compounds were less neurotoxic than phenytoin, carbamazepine and phenobarbital. All the compounds were completely non-toxic at 4h when compared to phenytoin, carbamazepine and phenobarbital, which were toxic at 100 and 300 mg/kg respectively. Compounds 2a, 2b, 2e, 2g and 2i emerged as the active compounds in oral MES screen. Selected compounds were evaluated for quantification studies in MES, scPTZ and neurotoxicity screens after i. p (2b, 2i) and oral administration (2a, 2g) in rats. Among all the compounds 2a, 2b and 2g emerged as broad-spectrum compounds as indicated by their protection in MES, scSTY and scPTZ screens. All the compounds except compound 2b showed significant sedative-hypnotic activity. Full article