Metabolomics Study on the Hepatoprotective Effect of Scoparone Using Ultra-Performance Liquid Chromatography/electrospray Ionization Quadruple Time-of-Flight Mass Spectrometry.
Metabolomics study on the hepatoprotective effect of scoparone using ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry.
Filed under: Drug and Alcohol Rehabilitation
Analyst. 2012 Nov 14;
Zhang A, Sun H, Dou S, Sun W, Wu X, Wang P, Wang X
Scoparone is an important constituent of Yinchenhao (Artemisia annua L.), a famous medicinal plant, and displayed bright prospects in the prevention and therapy of liver injury. However, the precise molecular mechanism of hepatoprotective effects has not been comprehensively explored. Here, metabolomics techniques are the comprehensive assessment of endogenous metabolites in a biological system and may provide additional insight into the mechanisms. The present investigation was designed to assess the effects and possible mechanisms of scoparone against carbon tetrachloride-induced liver injury. Ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-Q-TOF/MS) combined with pattern recognition approaches including principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were integrated to discover differentiating metabolites. Results indicate five ions in the positive mode as differentiating metabolites. Functional pathway analysis revealed that the alterations in these metabolites were associated with primary bile acid biosynthesis, pyrimidine metabolism. Of note, scoparone has a potential pharmacological effect through regulating multiple perturbed pathways to the normal state. Our findings also showed that the robust metabolomics techniques are promising for getting biomarkers and clarifying mechanisms of disease, highlighting insights into drug discovery.
HubMed – drug
Using droplet-based microfluidic technology to study the precipitation of a poorly water-soluble weakly basic drug upon a pH-shift.
Filed under: Drug and Alcohol Rehabilitation
Analyst. 2012 Nov 14;
Edwards F, Tsakmaka C, Mohr S, Fielden PR, Goddard NJ, Booth J, Tam KY
The purpose of this study is to develop a droplet-based microfluidic device capable of monitoring drug precipitation upon a shift from gastric pH (pH 1.5) to intestinal pH (pH 6.5-7.0). The extent of precipitation occurring in droplets over time was measured using a novel on-chip laser scattering technique specifically developed for this study. The precipitation of ketoconazole, a poorly water-soluble basic drug, was investigated under different concentrations and pH values. It has been shown that the drug precipitates rapidly under supersaturation. Two water-soluble aqueous polymers, namely, polyvinylpyrrolidone (PVP) and hydroxypropylmethylcellulose (HPMC) have been evaluated as precipitation inhibitors. HPMC was shown to be the most potent precipitation inhibitor. It is envisaged that the microfluidic pH-shift method developed in this study would form a proof-of-concept study, towards the development of a high throughput method for screening pharmaceutical excipients/precipitation inhibitors.
HubMed – drug
Substrate Mediated Enzyme Prodrug Therapy.
Filed under: Drug and Alcohol Rehabilitation
PLoS One. 2012; 7(11): e49619
Fejerskov B, Zelikin AN
In this report, we detail Substrate Mediated Enzyme Prodrug Therapy (SMEPT) as a novel approach in drug delivery which relies on enzyme-functionalized cell culture substrates to achieve a localized conversion of benign prodrug(s) into active therapeutics with subsequent delivery to adhering cells or adjacent tissues. For proof-of-concept SMEPT, we use surface adhered micro-structured physical hydrogels based on poly(vinyl alcohol), ?-glucuronidase enzyme and glucuronide prodrugs. We demonstrate enzymatic activity mediated by the assembled hydrogel samples and illustrate arms of control over rate of release of model fluorescent cargo. SMEPT was not impaired by adhering cells and afforded facile time – and dose – dependent uptake of the in situ generated fluorescent cargo by hepatic cells, HepG2. With the use of a glucuronide derivative of an anticancer drug, SN-38, SMEPT afforded a decrease in cell viability to a level similar to that achieved using parent drug. Finally, dose response was achieved using SMEPT and administration of judiciously chosen concentration of SN-38 glucuronide prodrug thus revealing external control over drug delivery using drug eluting surface. We believe that this highly adaptable concept will find use in diverse biomedical applications, specifically surface mediated drug delivery and tissue engineering.
HubMed – drug
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