Antiulcerogenic, Anti-Secretory and Cytoprotective Effects of Piper Cubeba (L.) on Experimental Ulcer Models in Rat

This paper evaluated anti-gastric ulcer and anti-secretory effects of a popular spice Piper cubeba L, (Family: Piperaceae) in rats. The gastric ulcer protective potential of an aqueous suspension of Piper cubeba (PCS) was evaluated against different acute gastric ulcer models in rats induced by pyloric ligation (Shay), hypothermic restraint stress, indomethacin and by necrotizing agents (80% ethanol, 0.2 M NaOH and 25% NaCl) induced gastric mucosal injury. Piper cubeba aqueous suspension (PCS) at the doses 250 and 500 mg/kg body weight administered orally (intraperitoneally in Shay rat model) showed a dose-dependent ulcer protective effects in all the above models. Besides, the PCS offered protection against ethanol-induced depletion of gastric wall mucus (GWM); replenished the reduced non-protein sulfhydryls (NP‑SH) concentration and significantly replenished malondialdehyde (MDA) contents in the gastric tissue. Ethanol induced histopathological lesions of the stomach wall characterized by mucosal hemorrhages and edema was reversed by Piper cubeba aqueous suspension treatment. Pretreatment of rats with Piper cubeba provided significant protection of gastric mucosa through its antioxidant capacity and/or by attenuating the offensive and by enhancing the defensive factor

Humoral and cellular immune responses to modified hepatitis B plasmid DNA vaccine in mice

Purpose: To evaluate the immunogenicity and types of immune response of a quality-controlled modified recombinant hepatitis B surface antigen (HBsAg) plasmid encoding HBsAg in mice.Methods: The characterized plasmid DNA was used in the immunization of Balb/c mice. Three groups of mice were intramuscularly injected with three different concentrations (50, 25 and 10 μg/100 μL) of the modified plasmid. Humoral immune response was monitored by enzyme-linked immunosorbent assay (ELISA), while cellular immune response was investigated by analysis of spleen cytokine profile (TNFα, IFN γ and IL2) as well as CD69 expression level in CD4 and CD8 positive cells.Results: In general, the activated CD4 cells showing intracellular cytokines were higher than CD8 positive population of cells (p < 0.05). These findings indicate that the vaccine induced both a humoral and cellular immunity. Cytokine profile also showed high levels of TNFα, IFN γ and IL2 and CD69 expression in the group of animals immunized at a dose of 10 μg when compared to control group (p < 0.05).Conclusion: A 10 μg dose intramuscular injection of the modified DNA-based vaccine encoding HBsAg in mice induces both high humoral and cellular immune responses.Keywords: Hepatitis B virus, Plasmid DNA, Vaccine, Spleen cytokines, Humoral and cellular immune response

Evaluation of Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for Poorly Water-Soluble Talinolol: Preparation, in vitro and in vivo Assessment

ObjectiveThe aim of this study was to investigate the in vitro and in vivo performance of self-nanoemulsifying drug delivery systems (SNEDDSs) of talinolol (TAL), a poorly water-soluble drug.MethodsSelf-nanoemulsifying drug delivery systems of TAL were prepared using various oils, non-ionic surfactants and/or water-soluble co-solvents and assessed visually/by droplet size measurement. Equilibrium solubility of TAL in the anhydrous and diluted SNEDDS was conducted to achieve the maximum drug loading. The in vitro dissolution experiments and human red blood cells (RBCs) toxicity test, ex vivo gut permeation studies, and bioavailability of SNEDDS in rats were studied to compare the representative formulations with marketed product Cordanum® 50 mg and raw drug.ResultsThe results from the characterization and solubility studies showed that SNEDDS formulations were stable with lower droplet sizes and higher TAL solubility. From the dissolution studies, it was found that the developed SNEDDS provided significantly higher rate of TAL release (>97% in 2.0 h) compared to raw TAL and marketed product Cordanum®. The RBC lysis test suggested negligible toxicity of the formulation to the cells. The ex vivo permeability assessment and in vivo pharmacokinetics study of a selected SNEDDS formulation (F6) showed about four-fold increase in permeability and 1.58-fold enhanced oral bioavailability of TAL in comparison to pure drug, respectively.ConclusionTalinolol loaded SNEDDS formulations could be a potential oral pharmaceutical product with high drug-loading capacity, improved drug dissolution, increased gut permeation, reduced/no human RBC toxicity, and enhanced oral bioavailability

Levocarnitine Improves AlCl3-Induced Spatial Working Memory Impairment in Swiss albino Mice

Background: Aluminum, a neurotoxic substance, causes oxidative stress induced-neurodegenerative diseases. Several lines of evidence suggest that levocarnitine has an antioxidant effect and also plays an important role in beta-oxidation of fatty acids. However, the role of levocarnitine in aluminum-induced neurotoxicity has not been well documented. Here we aimed to investigate the effect of levocarnitine on aluminum chloride (AlCl3)-induced oxidative stress and memory dysfunction.Methods: Male Swiss albino mice (n = 30) were treated with either control (saline) or AlCl3 or AlCl3 plus levocarnitine or levocarnitine or astaxanthin plus AlCl3 or astaxanthin alone. The spatial working memory was determined by radial arm maze (RAM). In addition, we measured the lipid peroxidation (MDA), glutathione (GSH), advanced oxidation of protein products (AOPP), nitric oxide (NO) and activity of superoxide dismutase (SOD) in the various brain regions including prefrontal cortex (PFC), striatum (ST), parietal cortex (PC), hippocampus (HIP) hypothalamus (HT) and cerebellum (CB). We used astaxanthin as a standard antioxidant to compare the antioxidant activity of levocarnitine.Results: The RAM data showed that AlCl3 treatment (50 mg/kg) for 2 weeks resulted in a significant deficit in spatial learning in mice. Moreover, aluminum exposure significantly (p < 0.05) increased the level of oxidative stress markers such as MDA, GSH, AOPP and NO in the various brain regions compared to the controls. In addition, combined administration of levocarnitine and AlCl3 significantly (p < 0.05) lowered the MDA, AOPP, GSH and NO levels in mice.Conclusion: Our results demonstrate that levocarnitine could serve as a potential therapeutic agent in the treatment of oxidative stress associated diseases as well as in memory impairment

Design and synthesis of multi-functional small-molecule based inhibitors of amyloid-β aggregation: Molecular modeling and in vitro evaluation.

Amyloid-β1-42 (Aβ42) peptide aggregate formation in the brain plays a crucial role in the onset and progression of Alzheimer's disease. According to published research, the Aβ monomer's amino acid residues KLVFF (16-20) self-associate to create antiparallel β-sheet fibrils. Small compounds can prevent self-assembly and destroy Aβ fibrils by attaching to the Aβ16-20 regions of Aβ42. To enhance biological characteristics and binding affinity to the amyloid beta peptide, β-sheet breaker small molecules can be developed and modified with various scaffolds. In the current study, a novel series of 2,3-disubstitutedbenzofuran derivatives was designed and created by fusing the benzofuran core of a known iron chelator, neuroprotective, and neurorestorative agent, like VK-28, with a motif found in the structure of a known muscarinic inhibitor and amyloid binding agent, like SKF-64346. Measurements of the binding affinity and in vitro aggregation inhibition of the Aβ42 peptide were made using the thioflavin T (ThT) test. Using AutoDock 4.2 software, molecular docking studies of the synthesized compounds were performed on the monomer and fibril structures of amyloid beta peptide. The compounds 8a-8g exhibited strong binding energy and affinity to Aβ fibrils as well as a 50%-67% reduction of the growth of Aβ aggregation. Finally, the positive traits of our recently synthesized compounds make them excellent candidates for additional in vivo testing as a "β-sheet breaking agent.

Antioxidant, Antibacterial, and Anticancer Activity of Ultrasonic Nanoemulsion of <i>Cinnamomum Cassia</i> L. Essential Oil

Cinnamomum cassia (C. assia) has long been used in traditional holistic medicine for its medicinal properties. It is used as an antioxidant, antibacterial, anti-inflammatory and anticancer agent. Cinnamon, in particular, the essential oil of C. cassia, has significant biological properties. Despite this, the volatility, stability, and insolubility of C. cassia essential oil (CEO) remain the main disadvantages that limit its application, ultimately affecting its pharmacological efficacy. To find a solution to this problem, we developed the CEO nanoemulsion (CEO-NE). For lipophilic compounds, insoluble nanoemulsion-based formulations are a popular delivery strategy. In this research work, a highly stable dosage form named CEO-NE was successfully developed using polysorbate 80 and water. The findings show that the synthesized CEO has a uniform shape with a PDI of 0.380 and an adequate particle size of 221.8 nm. The antioxidant outcomes show excellent results for CEO-NE compared to CEO against DPPH and hydrogen peroxide. The obtained antibacterial activity of CEO-NE was more efficient than that of CEO against Klebsiella pneumonia (MTCC 8911) with 0.025% and 0.05%, respectively. The CEO-NE preparation was tested against an alveolar lung adenocarcinoma cell line (A549) with an IC50 of 50.21 µg/mL for CEO and 18.05 µg/mL for CEO-NE, respectively. These results are encouraging for future translational studies on CEO-NE use in lung cancer therapy due to its excellent antioxidant, antibacterial, and killing kinetic properties

Herbal Fennel Essential Oil Nanogel: Formulation, Characterization and Antibacterial Activity against Staphylococcus aureus

Antimicrobial resistance (AMR) is one of the greatest threats to humanity in the world. Antibiotic-resistant bacteria spread easily in communities and hospitals. Staphylococcus aureus (S. aureus) is a serious human infectious agent with threatening broad-spectrum resistance to many commonly used antibiotics. To prevent the spread of pathogenic microorganisms, alternative strategies based on nature have been developed. Essential oils (EOs) are derived from numerous plant parts and have been described as antibacterial agents against S. aureus. Fennel essential oils were selected as antibacterial agents encapsulated in nanoparticles of polylactic acid and glycolic acid (PLGA). The optimum size of the formulation after loading with the active ingredient was 123.19 &plusmn; 6.1595 nm with a zeta potential of 0.051 &plusmn; 0.002 (23 &plusmn; 1.15 mV). The results of the encapsulation efficiency analysis showed high encapsulation of EOs, i.e., 66.4 &plusmn; 3.127. To obtain promising carrier materials for the delivery of fennel EOs, they were incorporated in the form of nanogels. The newly developed fennel oils in PLGANPs nanogels have good drug release and MIC against S. aureus. These results indicate the potential of this novel delivery system for antimicrobial therapy

Metabolomic and elemental analysis of camel and bovine urine by GC–MS and ICP–MS

Recent studies from the author’s laboratory indicated that camel urine possesses antiplatelet activity and anti-cancer activity which is not present in bovine urine. The objective of this study is to compare the volatile and elemental components of bovine and camel urine using GC–MS and ICP–MS analysis. We are interested to know the component that performs these biological activities. The freeze dried urine was dissolved in dichloromethane and then derivatization process followed by using BSTFA for GC–MS analysis. Thirty different compounds were analyzed by the derivatization process in full scan mode. For ICP–MS analysis twenty eight important elements were analyzed in both bovine and camel urine. The results of GC–MS and ICP–MS analysis showed marked difference in the urinary metabolites. GC–MS evaluation of camel urine finds a lot of products of metabolism like benzene propanoic acid derivatives, fatty acid derivatives, amino acid derivatives, sugars, prostaglandins and canavanine. Several research reports reveal the metabolomics studies on camel urine but none of them completely reported the pharmacology related metabolomics. The present data of GC–MS suggest and support the previous studies and activities related to camel urine

Development and validation of bioanalytical UHPLC-UV method for simultaneous analysis of unchanged fenofibrate and its metabolite fenofibric acid in rat plasma: Application to pharmacokinetics

A simple, precise, selective and fast ultra-high performance liquid chromatography (UHPLC-UV) method has been developed and validated for the simultaneous determination of a lipid regulating agent fenofibrate and its metabolite fenofibric acid in rat plasma. The chromatographic separation was carried out on a reversed-phase Acquity® BEH C18 column using methanol–water (65:35, v/v) as the mobile phase. The isocratic flow was 0.3 ml/min with rapid run time of 2.5 min and UV detection was at 284 nm. The method was validated over a concentration range of 100–10000 ng/ml (r2 ⩾ 0.9993). The selectivity, specificity, recovery, accuracy and precision were validated for determination of fenofibrate/fenofibric acid in rat plasma. The lower limits of detection and quantitation of the method were 30 and 90 ng/ml for fenofibrate and 40 and 100 ng/ml for fenofibric acid, respectively. The within and between-day coefficients of variation were less than 5%. The validated method has been successfully applied to measure the plasma concentrations in pharmacokinetics study of fenofibrate in an animal model to illustrate the scope and application of the method