Stimulatory effect of eurycomanone from Eurycoma longifolia Jack roots on dopamine secretion in human neuroblastoma SH-SY5Y cell line.

Eurycomanone has been identified as the major bioactive compound contributing to Eurycoma longifolia (EL) aphrodisiac activity, however, its mechanism of action remains obscured. Presently, eurycomanone was isolated from EL root extract and its molecular structure was identified. The human neuroblastoma SH-SY5Y cell line was differentiated into human dopaminergic neuron-like cells. Exogenous dopamine levels from the differentiated SH-SY5Y cells were quantified following the treatment of 5, 10, 15 µM of eurycomanone and 10 µM clorgyline as positive control. Dopamine secretion was significantly increased in a dose-dependent manner, compared to the vehicle control (p < .01) in differentiated SH-SY5Y cells. Dopamine concentration stimulated by 15 µM eurycomanone was significantly higher than clorgyline (p < .05), an inhibitor of monoamine oxidase A that suppresses dopamine catabolism. In conclusion, eurycomanone stimulated dopamine release of human SH-SY5Y neuron-like cells, which could be one of the mechanisms that underpin the aphrodisiac properties of the plant.

Implications of Low-concentration Polymer on the Physical Stability of Glassy Griseofulvin: Role of the Segmental Mobility.

Crystallization of amorphous pharmaceutical solids are widely reported to be affected by the addition of polymer, while the underlying mechanism require deep study. Herein, crystal growth behaviors of glassy griseofulvin (GSF) doped with various 1% w/w polymer were systematically studied. From the molecular structure, GSF cannot form the hydrogen bonding interactions with the selected polymer poly(vinyl acetate), polyvinyl pyrrolidone (PVP), 60:40 vinyl pyrrolidone-vinyl acetate copolymer (PVP/VA 64), and poly(ethylene oxide) (PEO). 1% w/w polymer exhibited weak or no detectable effects on the glass transition temperature (Tg) of GSF. However, crystal growth rates of GSF was altered from 4.27-fold increase to 2.57-fold decrease at 8 ℃ below Tg of GSF. Interestingly, the ability to accelerate and inhibit the growth rates of GSF crystals correlated well with Tg of polymer, indicating the controlling role of segmental mobility of polymer. Moreover, ring-banded growth of GSF was observed in the polymer-doped systems. Normal compact bulk and ring-banded crystals of GSF were both characterized as the thermodynamically stable form I. More importantly, formation of ring-banded crystals of GSF can significantly weaken the inhibitory effects of polymer on the crystallization of glassy GSF.

Anticancer effect of aromatic isoniazid derivatives in human gastric adenocarcinoma cells.

Current treatments for stomach cancer are often effective in curing cancer. However, these treatments can also have significant side effects, and they may not be effective in all cases. Hence synthetic compounds exhibit promise as potential agents for cancer treatment. In a previous study, we identified (E)-N'- (2,3,4-trihydroxybenzylidene) isonicotinohydrazide (ITHB4) as a novel antimycobacterial derivative of isoniazid with cytotoxic effects on the MCF-7 breast cancer cell line. This led us to investigate the potential anti-cancer properties of ITHB4 against adenocarcinoma gastric (AGS) cell line. The cytotoxic effect of ITHB4 has been determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and further confirmed for anticancer properties by means of apoptosis, reactive oxygen species (ROS), nuclear fragmentation, lactate dehydrogenase (LDH), caspases, cytokines and morphological including phenotypic changes of cells assay. The ITHB4 demonstrated a lower IC50 in inhibiting growth of AGS cells at 24 h compared to 48 and 72 h. ITHB4 has also shown no toxicity human immune cells. Treatment of ITHB4 against AGS for 24 h eventually lead to formation of early apoptotic AGS cells, reduced mitochondrial membrane potential, nuclear condensation, and nuclear fragmentation lastly increased in ROS levels together with the release of LDH, and secretion of caspases. The altered cytokine profile in ITHB4 treated AGS hints at the possibility that ITHB4 may possess anti-tumor and anti-inflammatory properties. Our results in this study demonstrate that ITHB4 has almost similar chemotherapeutic properties against gastric adenocarcinoma cells compared to breast cancer cell. This is suggesting that the anticancer capabilities of this compound should be in vivo and clinically assessed.

Bacterial Foodborne Illness in Malaysia: Terminalia spp. as a Potential Resource for Treating Infections and Countering Antibiotic Resistance.

Acute diarrhoea is becoming a major public health problem in Malaysia, with more than 13.5 million cases reported annually. Foodborne bacterial pathogens are a predominant cause of diarrhoea, with infections causing prolonged illness durations and higher patient mortality rates, placing a tremendous burden on the Malaysian economy. Due to increasing incidences of diarrhoea in Malaysia caused by foodborne pathogens and the increasing levels of resistance towards antibiotics from many different classes, new drugs and/or therapies are urgently required. The evidence for plants as new sources of antibiotics has increased dramatically in recent years and there has been a substantial increase in interest in traditional and herbal medicines. Several Terminalia spp. are native to Malaysia, with previous research demonstrating that Terminalia spp. are rich in therapeutic phytochemicals and possess antibacterial properties. However, limited research has been conducted on the native Malaysian Terminalia spp. for their potential as new antibacterial therapies. The current review discusses the types of bacteria, including antibiotic-resistant strains, that cause food poisoning in Malaysia, and reports the phytochemical content and antibacterial properties of eight of these useful plant species. Future directions pertaining to drug discovery pathways are also suggested.

Cytotoxic Activity of Isoniazid Derivative in Human Breast Cancer Cells.

BACKGROUND/AIM: Isoniazid is an antibiotic used for the treatment of tuberculosis. Previously, we found that the isoniazid derivative (E)-N'-(2,3,4-trihydroxybenzylidene) isonicotinohydrazide (ITHB4) could be developed as novel antimycobacterial agent by lead optimization. We further explored the ability of this compound compared to zerumbone in inhibiting the growth of MCF-7 breast cancer cells. MATERIALS AND METHODS: Cytotoxicity was measured by the MTT assay and further confirmed via apoptosis, ROS, cell cycle, DNA fragmentation and cytokine assays. RESULTS: ITHB4 demonstrated a lower IC50 compared to zerumbone in inhibiting the proliferation of MCF-7 cells. ITHB4 showed no toxicity against normal breast and human immune cells. Apoptosis assay revealed that ITHB4, at a concentration equal to the IC50, induces apoptosis of MCF-7 cells and cell cycle arrest at the sub-G1 and G2/M phases. ITHB4 triggered accumulation of intracellular ROS and nuclear DNA fragmentation. Secretion of pro-inflammatory cytokines induced inflammation and potentially immunogenic cell death. CONCLUSION: ITHB4 has almost similar chemotherapeutic properties as zerumbone in inhibiting MCF-7 growth, and hence provide the basis for further experiments in animal models.

Novel antimicrobial development using genome-scale metabolic model of Gram-negative pathogens: a review.

Antimicrobial resistance (AMR) threatens the effective prevention and treatment of a wide range of infections. Governments around the world are beginning to devote effort for innovative treatment development to treat these resistant bacteria. Systems biology methods have been applied extensively to provide valuable insights into metabolic processes at system level. Genome-scale metabolic models serve as platforms for constraint-based computational techniques which aid in novel drug discovery. Tools for automated reconstruction of metabolic models have been developed to support system level metabolic analysis. We discuss features of such software platforms for potential users to best fit their purpose of research. In this work, we focus to review the development of genome-scale metabolic models of Gram-negative pathogens and also metabolic network approach for identification of antimicrobial drugs targets.

Fabrication of Second Generation Smarter PLGA Based Nanocrystal Carriers for Improvement of Drug Delivery and Therapeutic Efficacy of Gliclazide in Type-2 Diabetes Rat Model.

Drug delivery and therapeutic challenges of gliclazide, a BCS class II drug used in type 2 diabetes mellitus (T2DM) can be overcome by exploring smarter carriers of second-generation nanocrystals (SGNCs). A combined method of emulsion diffusion, high-pressure homogenization and solvent evaporation method were employed in the preparation of gliclazide loaded poly (D, L-lactide-co-glycolide) (PLGA) SGNCs. Taguchi experimental design was adopted in fabrication of Gliclazide SGNc using Gliclazide -PLGA ratio at 1:0.5, 1:0.75, 1:1 with stabilizer (Poloxamer-188, PEG 4000, HPMC E15 at 0.5, 0.75, 1% w/v). The formulated gliclazide of SGNCs were investigated for physicochemical properties, in vitro drug release, and in vivo performance studies using type-2 diabetes rat model. The formulation (SGNCF1) with Drug: PLGA 1: 0.5 ratio with 0.5% w/v Poloxamer-188 produced optimized gliclazide SGNCs. SGNCF1 showed spherical shape, small particle size (106.3 ± 2.69 nm), good zeta potential (-18.2 ± 1.30 mV), small PDI (0.222 ± 0.104) and high entrapment efficiency (86.27 ± 0.222%). The solubility, dissolution rate and bioavailability of gliclazide SGNCs were significantly improved compared to pure gliclazide. The findings emphasize gliclazide SGNCs produce faster release initially, followed by delayed release with improved bioavailability, facilitate efficient delivery of gliclazide in T2DM with better therapeutic effect.