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Adenium obesum is a common plant found in many households in Malaysia. Its phytochemical constituents are believed to have contributed to its vast medicinal properties. Five types of compounds were isolated and identified from the plant, namely cardiac glycosides, pregnanes, triterpenes, flavonoids and carbohydrates. These compounds confer the plant its reported pharmacological activities such as antibacterial, antiviral, anticancer, antioxidant, immunomodulation and antiparasitic effects. The plant's antibacterial effects against some bacterial strains such as Proteus mirabilis and Pseudomonas aeruginosa were investigated while its antiviral activity was tested against H1N1. Its anticancer activity was found to be mediated through the hedgehog/GLI signalling pathway. For the immunomodulatory effect, A. obesum was found to promote proliferation of B and T cells. This review outlines in detail the pharmacological activities of A. obesum while further correlating these activities with the phytochemical constituents present. [ABSTRACT FROM AUTHOR]

Context: Liquid crystalline gel, self-assembled vesicular systems covered with nonionic surfactants, are promising for use in drug delivery. Aims: To develop and evaluate the liquid crystal (LC) systems of a combination of 5-fluorouracil and curcumin for a cervical cancer cell line. Methods: The LC was formulated using water, surfactant, and glycerin. Optimization was carried out by using different surfactants. The formulations were chosen for various studies, such as pH determination, environmental scanning electron microscopy (eSEM), Fourier transform infrared spectroscopy (FTIR) and dissolution study. The synergism of the combination of 5-FU and curcumin on cervical cancer HeLa cell line was then analyzed using CompuSyn software. Results: The formulations with 60% surfactant, the average particle size was in the ranges from 15.68 – 26.35 nm whereas with 40% surfactant, were 11.27 – 21.35 nm. The percentage of dissolution of 5-FU at pH 7 (PBS) A2: 40.23 > B2: 47.39 > X2: 50.36 > Y2: 56.36 compared to at pH 4 (vaginal simulated fluid, VSF) were A2: 36.23 > B2: 43.64 > X2: 45.67 > Y2: 49.01. The percentage of dissolution of curcumin of different formulations were at pH 7 (PBS) A2: 44.85 > B2: 51.36 > X2: 58.61 > Y2: 64.38 compared to at pH 4 (VSF) were A2: 41.03 > B2: 49.37 > X2: 57.85 > Y2: 68.75. Conclusions: The combination of the drugs showed that there was a synergistic effect when it was being administered together. The combination of drugs in LC system had a sustained release as well as it was effective against cervical cancer HeLa cell line.

Curcumin is a hydrophobic compound with good anti-proliferative, anti-oxidative, and anti-cancer properties but has poor bioavailability. Liquid crystals (LC) can accommodate both hydrophilic and hydrophobic drugs. The aim of this study was to formulate and evaluate a novel vaginal drug delivery system for cervical cancer using a curcumin LC system. The curcumin LC system was formulated using surfactant, glycerol, and water together with curcumin. Three types of surfactants were used to optimize the formulation, i.e., Tween 80, Cremphor EL, and Labrasol. The optimized formulations were subjected to physicochemical analysis, and their efficacy was evaluated in HeLa cells. The pH of the formulations was in the range of 3.91−4.39. Environmental scanning electron microscopy (ESEM) observations revealed spherical as well as hexagonal micelles. In vitro release of LC curcumin from vaginal simulated fluid (VSF, pH 4.5) showed a release from 20.47% to 87.25%. The IC50 of curcumin in HeLa cells was 22.5 μg/mL, while the IC25 and IC75 were 6.5 μg/mL and 35μg/mL, respectively. The cytotoxicity of the formulations was determined in comparison with liquid crystals without curcumin and pure curcumin by performing a t-test based on a significance level of p less than or equal to 0.05 (p ≤ 0.05). The curcumin LC system was able to release the required amount of drug and was effective against the cervical cancer cell line examined.

Introduction: The aging process is the most significant risk factor for developing Alzheimer's disease (AD). AD is the most common neurodegenerative disease that causes cognitive and memory impairment in the elderly. Excessive build-up of amyloid protein leads to cell death, brain atrophy, and cognitive and functional decline in AD. The nuclear factor kappa beta (NF-κB) is a family of inducible transcription factors composed of NF-κB1, NF-κB2, RelA, RelB and c-Rel. It is activated by genotoxic agents, as well as oxidative and inflammatory stresses. It regulates expression of genes that control apoptosis, cell cycle progression, cell senescence, and inflammation. NF-κB regulates amyloid precursor protein (APP) processing by activating transcription of β and γ secretases, which promotes amyloid dysregulation in AD. In addition, NF-κB activation is linked with many of the known lifespan regulators including insulin/IGF- 1, FOXO, SIRT, and mTOR. Therefore, NF-κB pathway contributes to the pathophysiology of AD. This study aims to evaluate the effects of APP overexpression on NF-κB pathway in neuronal cells. Methods: SH-SY5Y neuronal cells were transduced with APP plasmid. Overexpression of APP in the cells was validated by western blotting. Western blot analysis using antibodies targeting NF-κB signalling pathway was performed using the APP-overexpressed cells. Results: Overexpression of APP in cells caused a significant down-regulation of phosphorylated NF-κB. Overexpression of APP also slightly up-regulated IkappaB-alpha, IKK alpha, and IKK beta. Conclusion: APP overexpression affected NF-κB pathway by down-regulating NF-κB protein. [ABSTRACT FROM AUTHOR]

Introduction: Amyloid plaques, mainly comprising of amyloid-beta peptides derived from its precursor protein, are found deposited in hippocampal and entorhinal cortical regions of patients with Alzheimer's disease (AD). However, none led to a complete understanding of the molecular mechanisms of the AD in order to generate a new therapy that would eradicate the disease effectively. Activation of pro-apoptotic pathway was found to be associated with the accumulation of amyloid precursor protein (APP). The objective of this study is to examine theeffects of APP overexpression on the Bcl-2 family proteins involving in pro-apoptotic pathway in neuronal cells. Methods: The experiment was first performed with the transfection of HEK 293T cells for generation of lentiviral vector system consisting APP plasmid followed by transduction of SH-SY5Y neuronal cells using lentivirus generated. Subsequently, western blot analysis was conducted to validate the APP overexpression in SH-SY5Y cells. Then, expression levels of Bcl-2 family proteins in the APP overexpressed cells were determined by western blot analysis. The statistical analysis was performed by Microsoft Excel with Student's t-test. Results: APP overexpression in SH-SY5Y cells slightly upregulated the pro-apoptotic proteins including Bad, Bid, Bok and Puma but slightly downregulated Bcl-2, Bim and Bax. Conclusion: Our data suggest that APP overexpression regulated the Bcl-2-mediated pathway by a significant downregulation of Bim protein in neuronal cells. [ABSTRACT FROM AUTHOR]