Subject(s)
Arthritis, Gouty , Gout , Hyperuricemia , Animals , Disease Models, Animal , Mice , Uric AcidABSTRACT
In this investigation, the antibacterial modes of action of Radix Tinosporae, its major single components, and nine antibiotics with different targets or modes-of-action on Staphylococcus aureus were studied. Metabolic profiles of cultures treated with different medicines were acquired by HPLC/ESI-MS. After HPLC-MS data pretreatment, those profiles acquired were reduced into several MS vectors. Then statistical processing by principal components analysis was carried out upon those vectors, two conclusions could be drawn: (1) the antibacterial mode of action of Radix Tinosporae is similar to that of rifampicin and norfloxacin, which act on nucleic acid; (2) its active components playing main antimicrobial roles on Staphylococcus aureus might be alkaloids, such as palmatine and jatrorrhizine.
Subject(s)
Anti-Bacterial Agents/pharmacology , Staphylococcus aureus/drug effects , Tinospora/chemistry , Chromatography, High Pressure Liquid , Mass Spectrometry , Microbial Sensitivity Tests , Plant Extracts/analysis , Plant Extracts/chemistry , Plant Extracts/pharmacology , Principal Component AnalysisABSTRACT
In this investigation, metabolic profiles of Staphylococcus aureus treated by berberine and nine antibacterial substances with known modes of action were acquired by HPLC/ESI-MS. After data pretreatment, those profiles acquired were reduced into several MS vectors. Then, principal component analysis was carried out upon those vectors to classify those drugs according to their mechanisms. From the result obtained by principal component analysis, the possible antibacterial mode of berberine was evaluated.
Subject(s)
Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/pharmacology , Berberine , Chromatography, Liquid/methods , Principal Component Analysis/methods , Spectrometry, Mass, Electrospray Ionization/methods , Staphylococcus aureus/drug effects , Anti-Bacterial Agents/classification , Berberine/analysis , Berberine/pharmacology , Chromatography, Liquid/instrumentation , Feasibility Studies , Hot Temperature , Methanol/chemistry , Microbial Sensitivity Tests , Reproducibility of Results , Staphylococcus aureus/genetics , Water/chemistryABSTRACT
Traditional Chinese medicines have been used for thousands of years and are still being used as one of the regular treatments for many diseases. However, their mechanisms were still unknown. In this investigation, a possible procedure combining metabonomics and principal component analysis to investigate antibacterial modes of action and find main antimicrobial component in traditional Chinese medicine, Aquilegia oxysepala, is developed. Metabolic profiles of Staphylococcus aureus treated with nine antibiotics of known modes of action and with A. oxysepala were acquired by HPLC/DAD/ESI-MS. After statistical processing by principal components analysis on metabolic profiles, two conclusions could be drawn: (1) the target of A. oxysepala may be similar to that of lincolmensin, erythromycin, chloromycetin, streptomycin, and acheomycin, whose targets are protein; (2) its bioactive component playing main antimicrobial roles on S. aureus may be maguoflorine.
Subject(s)
Anti-Bacterial Agents/pharmacology , Aquilegia/metabolism , Chemistry, Pharmaceutical/methods , Plant Extracts/analysis , Apigenin/chemistry , Berberine/chemistry , Chromatography, High Pressure Liquid , Drug Design , Fluorine/chemistry , Medicine, Chinese Traditional , Models, Chemical , Molecular Conformation , Plants, Medicinal/metabolism , Principal Component Analysis , Spectrometry, Mass, Electrospray IonizationABSTRACT
A sensitive liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method is developed and validated for rapid determination of amantadine in human plasma. Desloratadine was used as the internal standard (I.S.). Human plasma (0.2 mL) was first alkalified with 100 microL of sodium hydroxide (3M) and then extracted with 1 mL of n-hexane containing 1% isopropanol (v/v) and 10% dichloromethane (v/v) by vortex-mixer for 3 min. The mixture was centrifuged at 14,000 rpm for 5 min. The supernatant was evaporated to dryness and the residue was dissolved in mobile phase. Samples were separated using a Thermo Hypersil-HyPURITYC18 reversed-phase column (150 mm x 2.1 mm i.d., 5 microm). Mobile phase consisted of methanol-acetonitrile-20 mM ammonium acetate (45:10:45, v/v/v) containing 1% acetic acid with pH 4.0. Amantadine and I.S. were measured by electrospray ion source in positive selective ion monitoring mode. The good linearity ranged from 3.9 to 1000 ng/mL and the lowest limit of quantification was 3.9 ng/mL. The extraction efficiencies were approximately 70% and recoveries of method ranged from 98.53 to 103.24%. The intra-day relative standard deviations (R.S.D.) were less than 8.43% and inter-day R.S.D. below 10.59%. The quality control samples were stable when kept at room temperature for 12h, at -20 degrees C for 30 days and after four freeze/thaw cycles. The method has been successfully used to evaluation of the pharmacokinetics and bioequivalence of amantadine in 20 healthy volunteers after an oral dose of 100 mg amantadine.
Subject(s)
Amantadine/blood , Antiparkinson Agents/blood , Antiviral Agents/blood , Chromatography, Liquid/methods , Mass Spectrometry/methods , Amantadine/chemistry , Amantadine/pharmacokinetics , Antiparkinson Agents/pharmacokinetics , Antiviral Agents/pharmacokinetics , Humans , Molecular Structure , Reproducibility of ResultsABSTRACT
The rapid development of systems biology and especially the advances in the high-throughput and comprehensive research technologies and research idea in metabonomics provide new strategies in the analysis of active components in the formula of traditional Chinese medicine (TCM) and pharmacokinetic analysis of their metabolites in vivo. Furthermore, the initiatives of metabonomics may pave a new way to explain the action mode of TCM in the light of modern sciences, while the metabonomic research achievements may contribute to the establishment of a new technique platform for evaluating the efficacy of the formula of TCM.
