Bulletin of Faculty of Pharmacy, Cairo University最新文献

Background

Oxidized low density lipoprotein (oxLDL), anti-oxLDL antibodies (oxLDL Ab) and lipoprotein-associated phospholipase A2 (Lp-PLA2) are the sequel of lipoprotein oxidation and were not studied contemporarily in obese adolescents with and without type 1 diabetes (T1DM).

Subjects and methods

The current study enrolled seventy-five adolescents with T1DM who were selected as having hyperglycemia and seventy-five matched control subjects. Both the diabetic and the control groups were further divided into obese, normal weight and underweight subgroups according to body mass index (BMI). The following tests were performed: fasting plasma glucose (FG) glycated hemoglobin (HbA1c), insulin, apolipoprotein AI (apo AI), apolipoprotein B (apo B), oxLDL, oxLDL Ab and Lp-PLA2 mass. The diabetic subgroups were selected as having hyperglycemia.

Results

Obese diabetic subgroup had higher insulin level and HOMA value than underweight and normal weight diabetic subgroups. oxLDL, oxLDL Ab and Lp-PLA2 showed higher concentrations in patients with T1DM than in control subjects (118.48 ± 23.7, 1231.8 ± 940 and 401.26 ± 97.2 vs. 58.1 ± 17.9, 424.9 ± 290.0 and 315.7 ± 70; p < 0.001).. In patients with T1DM, direct correlations were found between oxLDL, oxLDL Ab and Lp-PLA2 and cardiometabolic markers represented by apo B/apo AI ratio, FG and BMI.

Conclusion

The current data provide evidence that oxLDL, its retroactive enzyme and antibody are present in circulation early in childhood when primed by obesity and hyperglycemia in T1DM and suggests that they could be useful markers for cardiovascular diseases (CVD).

Liver diseases represent one of major health burdens worldwide, both oxidative stress and inflammation play crucial roles in the development of liver diseases. Resveratrol (RSV), a naturally occurring compound, has recently been shown to exert anti-oxidative and anti-inflammatory actions. This work aimed to investigate the prophylactic effect of RSV against CCl₄-induced hepatotoxicity in experimental rats in terms of inflammatory interleukins and histopathological changes. Twenty-four adult male rats were divided into three equal groups: group A: Negative control, received oral vehicle, group B: Positive control, received oral vehicle for 6 days and on 6^th day injected with single dose of CCl₄, and group C: RSV-treated group, received oral RSV (25 mg/kg/day) for 6 days and on 6^th day injected with single dose of CCl₄. 24 h after induction of hepatotoxicity by CCl₄, all rats were sacrificed; liver was excised for histopathological studies and blood samples were collected. ALT, AST, ALP, total bilirubin, IL-1β, IL-6, and IL-10 were determined in plasma while total GSH, MDA, GPx, and SOD were assayed in liver homogenate. Plasma levels of ALT, AST, ALP, total-bilirubin, IL-1β, and IL-6 were significantly increased 24 h after induction of hepatotoxicity by CCl₄ while IL-10 decreased. Pretreatment of rats with RSV prevented these changes. The histopathological changes were less obvious in livers of RSV-treated rats in comparative to positive control. In conclusion, RSV has a prophylactic effect against hepatotoxicity induced by CCl₄ through decreasing the inflammatory interleukins level.

Drug discovery include drug designing and development, is a multifarious and expensive endeavor, where least number of drugs that pass the clinical trials makes it to market. Software based drug discovery and development methods have major role in the development of bioactive compounds for over last three decades. Novel software based methods such as molecular modeling, structure-based drug design, structure-based virtual screening, ligand interaction and molecular dynamics are considered to be powerful tool for investigation of pharmacokinetic and pharmacodynamic properties of drug, and structural activity relationship between ligand and its target. Computational approaches such as docking confer interaction of small molecules with structural macromolecules and thereby hit identification and lead optimization. These methods are faster, and accurately provide valuable insights of experimental findings and mechanisms of action. In addition, appropriate implementation of these techniques could lead to a reduction in cost of drug designing and development. Currently in biomedicine sciences these software are exhibiting imperative role in the different phases of drug discovery. The review discusses working principle and successful applications of most commonly used software for drug designing and development.

In present study HPTLC method was developed and validated for the determination of friedelin in Putranjiva roxburghii Wall (family: Euphorbiaceae) leaf, bark extract and in polyherbal formulations. Analysis of samples were performed on TLC aluminium precoated plate (60 F₂₅₄) by using mobile phase toluene: chloroform (9:1 v/v). Plate was derivatized with vanillin sulphuric acid and scanned at 580 nm. Developed method found to give compact spot for friedelin at R_f value 0.43 ± 0.01. The method was validated using International Council for Harmonization (ICH) guidelines including linearity, precision, accuracy, and robustness. Friedelin was found to be present in leaf extract of Putranjiva roxburghii Wall (0.003% w/w), in bark (0.04% w/w), formulation 1 (0.002% w/w) and formulation 2 (0.035% w/w). A good linearity relationship was found to be (100–500 ng spot⁻¹) with correlation coefficient (r²) value of 0.9892 for friedelin. Limit of detection and limit of quantitation was found to be 32.15, 97.44 ng/band respectively for friedelin. The developed method was found to be accurate and precise with 0.78%, 0.9% (%RSD) for interday and intraday precision. Accuracy of the method was performed by recovery studies at three different concentration levels and the average percentage recovery was found to be 98.55% for friedelin. The proposed method for the quantitation of friedelin was found to be simple, specific, accurate and robust in Putranjiva roxburghii Wall and polyherbal formulations.

Cancer is the second leading cause of death world-wide. One of the most important medical practices of the 21st century is the chemoprevention of cancer. For a long history, it has been accepted that plants could prevent and exert suitable anti-carcinogenic effects for multiple types of cancers. Seriphidium herba-alba family Asteraceae has been used in the folk medicine by many cultures for treatment of various ailments since ancient times. In the current research we were aimed to evaluate the cancer chemopreventive activity of two crude extracts of S. herba-alba, methylene chloride extract and methanol extract on two cell lines: Human breast cancer cells (MCF-7) and human hepatocellular carcinoma cells (Hep-G2). Assessment of cytotoxicity using methyl thiazole tetrazolium (MTT assay) indicated that both extracts exhibit poor cytotoxicity with half maximal inhibitory concentration (IC₅₀) >20 µg/mL. Assessment of glutathione-S-transferases (GSTs) activity (spectrophotometrically) showed statistically significant enhancement of enzyme activity after treatment with three different doses of methylene chloride extract and glutathione (GSH) concentrations were decreased. Analysis of cell mode of death by Ethidium bromide/Acridine orange (EB/AO) staining revealed that the dominant mode of death in MCF-7 cells was apoptosis. Assessment of vascular endothelial growth factor (VEGF) and platelets derived growth factor (PDGF_BB) using ELISA showed that VEGF and PDGF_BB levels were statistically significant decreased. In Conclusion: both extracts may be cancer chemopreventive agents since they had tumor anti-initiating, and anti-promoting activity.

Three ion selective electrodes were developed for the quantification of Tiemonium methylsulphate (TIM). Two of these sensors involve the construction of water insoluble ion-association complexes; namely sensor1 TIM-phosphotungstate (TIM-PT) and sensor 2 TIM-Reinecke (TIM-R). Molecular recognition elements have extensive applications in electrochemical sensors with a significant potential for future development thus a third electrode utilizing molecularly imprinted polymer was constructed; sensor 3 TIM-MIP. The proposed sensors showed fast, stable Nernstian responses of 56.4, 56.1and 57.5 mV/decade for sensors 1, 2 and 3, respectively, across a relatively wide TIM concentration range (1 × 10⁻⁴ to 1 × 10⁻² mol L⁻¹ for sensors 1 and 2 and 1 × 10^–5 to 1 × 10^–2 mol L⁻¹ for sensor 3) in the pH range of 2–7. Sensor 1 and sensor 2 can be used for five weeks while sensor 3 for 65 days without a significant change in sensitivity. The suggested method was used to determine TIM in dosage forms. No measurable difference was obtained when the result statistically compared with respect to accuracy and precision with reported HPLC method.

Ficus dalhousiae stem bark is used to treat cancer and hyperlipidemia in folklore practices. F. dalhousiae stem bark methanolic extract (250 and 500 mg/kg b. wt.) was evaluated for antihyperlipidemic activity in Triton WR-1339 and high fat diet-induced hyperlipidemic rats. F. dalhousiae extract significantly (P ⩽ 0.005) alter the serum TC, TG, LDL-C and HDL-C levels to near normal in Triton WR-1339 and high fat diet-induced hyperlipidemic rats. The liver total cholesterol and triglycerides were also significantly reduced after treatment with 250 and 500 mg/kg of F. dalhousiae. The result of this study indicates that F. dalhousiae has a significant potential to use as a natural antihyperlipidemic agent.

Objective

The objective of the present investigation was to evaluate the hypoglycemic potential of Berberis aristata and Tamarindus indica using various in vitro techniques.

Methods

The selected plant extracts were studied for their effects on glucose adsorption capacity, in vitro glucose diffusion, in vitro amylolysis kinetics and glucose transport across the yeast cells.

Results

It was observed that both the plant extracts adsorbed glucose and the adsorption of glucose increased remarkably with an increase in glucose concentration. No significant (p ⩽ 0.05) differences were observed between the adsorption capacities of B. aristata and T. indica. The results of amylolysis kinetic experimental model exhibited that the rate of glucose diffusion was increased with time from 30 to 180 min and both the plant extracts demonstrated significant inhibitory effects on movement of glucose into external solution across dialysis membrane as compared to control. It was observed that the plant extracts also promoted glucose uptake by the yeast cells. Enhancement of glucose uptake was dependent on both the sample and glucose concentration. B. aristata extract exhibited significantly higher (p ⩽ 0.05) activity than the extract of T. indica at all concentrations.

Conclusion

The results of the study verified the hypoglycemic activity of the extracts of B. aristata and T. indica. However, the observed effects need to be confirmed using different in vivo models and clinical trials for their effective utilization as therapeutic agents.

Quercetin is a well-known flavonoid, has low bioavailability. Quercetin nanoparticles (NQC) enhance its bioavailability. NQC were not explored for their potential therapeutic activities in Alzheimer’s disease (AD). Hence, the present study was performed to evaluate the protective effect of NQC in comparison to free quercetin against scopolamine induced spatial memory impairments.

NQC prepared by anti solvent precipitation method. Quercetin, NQC (30 mg/kg p.o.) and rivastigmine (2 mg/kg i.p.) as a reference drug were administered for 8 consecutive days. At the end of the treatment period memory impairments were induced by a single injection of scopolamine (20 mg/kg; i.p.). Conditioned avoidance and rectangular-maze tests were conducted 30 min thereafter then rats were sacrificed and brain homogenates were used for the estimation of glutathione (GSH), catalase and malondialdehyde (MDA) contents together with acetyl cholinesterase (AchE) activity. In addition, histopathologic studies were also performed.

The size of NQC was observed below 300 nm. NQC significantly reduced the transfer latency and conditioned avoidance response compared to scopolamine treated group (p < 0.05). Pretreatment with NQC showed a significant (p < 0.05) decrease in MDA, AchE levels and increase in brain catalase and GSH levels to be similar to that observed in the rivastigmine group.

In all the behavioral, biochemical and histological experiments, the rats treated with NQC showed additional distinguished results compared to quercetin group indicating that a preventive strategy against the progression of AD. This approach of quercetin nanoparticles provides the potential therapeutic application in human neurodegenerative disease in future.

The objective of this study is to enhance the dissolution properties of leflunomide, a class BCS-II drug by incorporating the self emulsifying (SE) form of the drug onto liquisolid systems in the form of tablets. Different formulae were prepared by dissolving leflunomide in PEG300 then forming SE systems using tween 80 as surfactant and either sesame oil and paraffin oil then adsorbing on powder excipients to form SE liquisolid powders. The prepared powders showed adequate flowability. The drug and excipients showed compatibility by analysis with DSC, XRD and FTIR. After compression, all tablets showed adequate weight variation, friability and disintegration time with disintegration time ranging between 8.45 ± 0.16 min and 10.7 ± 0.29 min. All liquisolid tablets exhibited higher in vitro dissolution in distilled water compared to physical mixture and the commercial tablets (Arthfree®) with formula containing sesame oil and highest amount of solvent (TS04) exhibiting the highest dissolution profile and it did not change by the change in the pH of the dissolution medium. The tablets showed stability during a 6 months accelerated stability study according to appearance, drug content, disintegration time and dissolution profile. Thus it can be concluded that combining self emulsifying drug delivery technique and liquisolid technology can be a promising tool to enhance the dissolution profile of leflunomide in vitro.