Cytotoxic and antimicrobial activities of alkaloids from tabernaemontana corymbosa

The investigations were made based on the fact that alkaloids from Apocynaceae family are potential for medicinal purposes. The aim of the study was to explore the potential cytotoxic and antimicrobial activities of alkaloids extracted from T. corymbosa and to provide scientific basis for further studies of T. corymbosa. The alkaloids were extracted from stembarks of Tabernaemontana corymbosa using maceration and acid-base extraction methods. Then, the extracts were tested for their cytotoxic and antimicrobial activities. The cytotoxic activity was studied in vitro using human non-small lung carcinoma (A549) and human cervical carcinoma (C33A). The cells were exposed to three crude alkaloid extracts of T. corymbosa. The cytotoxic effects of these crude alkaloid extracts were evaluated by MTT assay. In antimicrobial activity study, the crude alkaloid extracts of T. corymbosa were tested against four bacterial and two fungi species by using disc diffusion method. Bacillus cereus ATCC11778, Pseudomonas aeruginosa ATCC27853, Staphylococcus aureus ATCC25923, Escherichia coli ATCC35218, Cryptococcus neoformans ATCC90112 and Candida albicans ATCC10231 were used in the study. Cytotoxicity study showed that only crude B alkaloids exhibited cytotoxic effect against A549 and C33A cancer cells, giving an IC50 as low as 7.81 μg/mL and 3.91 μg/mL, respectively. In antimicrobial activity, the zones of inhibition against the tested bacteria were found in the range of 7.00 to 14.75 mm, along with their MIC and MBC/MFC values ranging from 0.37-1.11 mg/mL and 3.33-10.00 mg/mL, respectively. Those results suggest that T. corymbosa contains alkaloids that active as cytotoxic and antimicrobial agents

The efficiency of convergence rate for IMSS2-5D procedure

A new iterative procedure is formulated in this paper known as the interval midpoint symmetric single-step IMSS2-5D procedure. In this paper, we consider this new procedure in order to describe the rate of convergence of the IMSS2-5D procedure. It is analytically proven that the IMSS2-5D procedure has a higher convergence rate than ISS2 and ISS2-5D, verifying the rate of convergence to be at least 12. Hence, computational time is reduced since this procedure is more efficient for bounding simple zeros simultaneously. Hence, it would be effective to use this procedure in determining the zeros of polynomial simultaneously

Comparative assessment of plasmid DNA delivery by encapsulation within or adsorbed on poly (D, L-lactide-co-glycolide) nanoparticles

Purpose: To compare the gene delivery effectiveness of plasmid DNA (pDNA) encapsulated within poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles with that adsorbed on PLGA nanoparticles. Methods: PLGA nanoparticles were prepared using solvent-evaporation method. To encapsulate pDNA within the particles, it was first complexed with cetyltrimethylammonium bromide (CTAB) and then added to the oil phase during the synthesis. For the adsorption, PLGA nanoparticles were first modified with either CTAB or chitosan and then pDNA was adsorbed on the particle surface by electrostatic interaction. Results: Nanoparticles encapsulating pDNA exhibited better plasmid loading and protection with significantly lower burst release (p < 0.05) compared to that of the nanoparticles with adsorbed plasmid. Cell uptake of chitosan-modified nanoparticles by murine neuroblastoma (N2a) cells was significantly (p < 0.05) higher than that of chitosan-free nanoparticles. Nanoparticles encapsulating pDNA showed higher transfection efficiency (p < 0.05) in N2a cells. Conclusion: Encapsulation of pDNA within PLGA nanoparticles presents a potential strategy for gene delivery that is superior to pDNA adsorbed on the nanoparticle surface. In addition, encapsulation keeps the particle surface free for further modifications such as the addition of targeting ligands

Method development and validation using UV spectrophotometry for Nigella sativa oil microparticles quantification

Nigella sativa oil (NSO) has been exploited for medical purposes for many generations. The fabrication of microparticles containing NSO intended for sustained release was done to be used in treating osteomyelitis. Method in quantifying NSO using UV-spectroscopy was developed and validated. Linearity shown a good correlation coefficient with the values higher than 0.995, both for actual and different analysts. The LOD and LOQ values were recorded to be 2.89 μg/mL and 8.75 μg/mL respectively. In addition, the highest %RSD values for the intermediate and repeatability studies were 0.970% and 0.445% which suggested the method was precise. The percentage recovery for 4 known concentrations gave the range between 98.16% to 99.39%, indicating the high accuracy of the method. The parameters analyzed in this study were in accordance with ICH Q2 (R1) guidelines

Prospective stem cell lines as in vitro neurodegenerative diseases models for natural product research

The use of in vitro model for screening pharmacological compounds or natural products has gained global interest. The choice of cells to be manipulated plays a vital role in coming up with the best-suited model for specific diseases, including neurodegenerative diseases (ND). A good in vitro ND model should provide appropriate morphological and molecular features that mimic ND conditions where it can be used to screen potential properties of natural products in addition to unravelling the molecular mechanisms of ND. In this mini review, we intend to demonstrate two prospective stem cell lines as the potential cell source for in vitro ND model and compare them to the commonly used cells. The common source of cells that have been used as the in vitro ND models is discussed before going into details talking about the two prospective stem cell lines

Crossing the blood-brain barrier: a review on drug delivery strategies for treatment of the central nervous system diseases

Many drugs have been designed to treat diseases of the central nervous system (CNS), especially neurodegenerative diseases. However, the presence of tight junctions at the blood-brain barrier has often compromised the efficiency of drug delivery to target sites in the brain. The principles of drug delivery systems across the blood-brain barrier are dependent on substrate-specific (i.e. protein transport and transcytosis) and non-specific (i.e. transcellular and paracellular) transport pathways, which are crucial factors in attempts to design efficient drug delivery strategies. This review describes how the blood-brain barrier presents the main challenge in delivering drugs to treat brain diseases and discusses the advantages and disadvantages of ongoing neurotherapeutic delivery strategies in overcoming this limitation. In addition, we discuss the application of colloidal carrier systems, particularly nanoparticles, as potential tools for therapy for the CNS diseases

Comparative assessment of poly (D, L-lactide-co-glycolide) nanoparticles modified by either cetyltrimethylammonium bromide or chitosan for plasmid DNA adsorption

Purpose: To evaluate poly (D,L-lactide-co-glycolide) PLGA nanoparticles modified by cetyltrimethyl ammonium bromide (CTAB) or chitosan for plasmid DNA adsorption. Methods: PLGA nanoparticles were prepared by solvent diffusion method and modified by including CTAB in the aqueous (F1) or oil phase (F2), or by including low (F3) or medium (F4) molecular weight chitosan. The nanoparticles were characterised by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), as well as for cell toxicity, cell uptake and transfection. Results: CTAB failed to confer positive charge on the nanoparticles. CTAB desorbed easily from F1 surface. This resulted in negative zeta potential, increased cytotoxicity as well as decreased cell uptake and transfection. In F2, CTAB was located mainly in PLGA matrix, resulting in negative charge with decreased cytotoxicity, and increased cell uptake and transfection compared to F1. On the other hand, chitosan-modified nanoparticles (F3 and F4) showed stronger interaction between chitosan and PLGA, leading to positively-charged particles, decreased cytotoxicity, as well as increased cell uptake and transfection. Amongst the four formulations, F4 exhibited the highest transfection. Conclusion: These results should aid in understanding how PLGA nanoparticles are modified by CTAB and chitosan. Modification with chitosan yields PLGA nanoparticles with higher DNA adsorption and transfection with lower cytotoxicity

Asymptomatic neurotoxicity of amyloid β-peptides (Aβ1-42 and Aβ25-35) on mouse embryonic stem cell-derived neural cells

One of the strategies in the establishment of in vitro oxidative stress models for neurodegenerative diseases, such as Alzheimer’s disease (AD), is to induce neurotoxicity by amyloid beta (Aβ) peptides in suitable neural cells. Presently, data on the neurotoxicity of Aβ in neural cells differentiated from stem cells are limited. In this study, we attempted to induce oxidative stress in transgenic 46C mouse embryonic stem cell-derived neurons via treatment with Aβ peptides (Aβ1-42 and Aβ25-35). 46C neural cells were generated by promoting the formation of multicellular aggregates, embryoid bodies in the absence of leukemia inhibitory factor, followed by the addition of all-trans retinoic acid as the neural inducer. Mature neuronal cells were exposed to different concentrations of Aβ1-42 and Aβ25-35 for 24 h. Morphological changes, cell viability, and intracellular reactive oxygen species (ROS) production were assessed. We found that 100 µM Aβ1-42 and 50 µM Aβ25-35 only promoted 40% and 10%, respectively, of cell injury and death in the 46C-derived neuronal cells. Interestingly, treatment with each of the Aβ peptides resulted in a significant increase of intracellular ROS activity, as compared to untreated neurons. These findings indicate the potential of using neurons derived from stem cells and Aβ peptides in generating oxidative stress for the establishment of an in vitro AD model that could be useful for drug screening and natural product studies

Insights into the neuropathology of cerebral ischemia and its mechanisms

Cerebral ischemia is a result of insufficient blood flow to the brain. It leads to limited supply of oxygen and other nutrients to meet metabolic demands. These phenomena lead to brain damage. There are two types of cerebral ischemia: focal and global ischemia. This condition has significant impact on patient's health and health care system requirements. Animal models such as transient occlusion of the middle cerebral artery and permanent occlusion of extracranial vessels have been established to mimic the conditions of the respective type of cerebral ischemia and to further understand pathophysiological mechanisms of these ischemic conditions. It is important to understand the pathophysiology of cerebral ischemia in order to identify therapeutic strategies for prevention and treatment. Here, we review the neuropathologies that are caused by cerebral ischemia and discuss the mechanisms that occur in cerebral ischemia such as reduction of cerebral blood flow, hippocampal damage, white matter lesions, neuronal cell death, cholinergic dysfunction, excitotoxicity, calcium overload, cytotoxic oedema, a decline in adenosine triphosphate (ATP), malfunctioning of Na+/K+-ATPase, and the blood-brain barrier breakdown. Altogether, the information provided can be used to guide therapeutic strategies for cerebral ischemia