The development of new chiral stationary phases has been very important in the a ccurate analysis of drug enantiomers and their metabolites in biological samples during drug discovery and development. New chiral stati...The development of new chiral stationary phases has been very important in the a ccurate analysis of drug enantiomers and their metabolites in biological samples during drug discovery and development. New chiral stationary phases have been d eveloped using conalbumin and flavoprotein from chicken egg whites, which have b een applied to a broad range of drug enantiomers. The application and characteri zation of these two chiral columns for high-performance liquid chromatograp hy have been documented. Both specific and non-specific interactions, based on the silica gel surface and linker moiety, influenced retention and chiral separa tion of solutes. Interactions between drug enantiomers and proteins, as a pseudo chiral stationary phase, were investigated with affinity capillary electrophore sis, in order to avoid the effects of non-specific interactions. The chiral dis crimination region for ketoprofen on the flavoprotein surface was concluded to c onsist of an α-helix structure. Studies with chemically modified flavoprot ein indicated that two types of interactions at the chiral discrimination region were required for chiral separation: a π-π interaction between a tryptophan residue and the aromatic ring of ketoprofen, and an ionic interaction between th e carboxyl group of ketoprofen and an amino and carboxyl group of the protein. I n the bod y, drugs and biologically active substances having a carboxyl group have been kn own to transform various metabolites such as acyl glucuronide. The acyl adenylat e has also been noted as a chemically active intermediate of coenzyme A ligation . Both the acyl adenylate and the acyl glucuronide produced protein adducts by r eacting with nucleophilic groups such as amino groups on protein molecules. To c haracterize both active intermediates and protein adducts, analytical techniques conferring highly selective molecular recognition, such as high-performance li quid chromatography and mass spectrometry, were required.展开更多
OBJECTIVE Brahmi(Bacopa monnieri Wettst.,Schrophulariaceae)has been used in Ayuravedic medicine as a memory enhancer.We aimed at research and development of Brahmi for clinical use as the food supplement for memory im...OBJECTIVE Brahmi(Bacopa monnieri Wettst.,Schrophulariaceae)has been used in Ayuravedic medicine as a memory enhancer.We aimed at research and development of Brahmi for clinical use as the food supplement for memory improvement.METHODS The standardized extract of Brahmi has been developed.The neuroprotective effect of the extract was tested using in vitro and in vivo assay.A double-blinded randomized control trial of brahmi tablet was conducted in 60 middle-aged elderly volunteers.RESULTS The in vivo studies indicated that the standardized extract had neuroprotective effect at the doses of 40 and 80mg·kg-1.The escape latency time of rats in Morris water maze test was reduced.Moreover,the reduction of neurons and cholinergic neuron densities were mitigated.We also tested its protection effect against the beta-amyloid protein and glutamate-induced neurotoxicity in primary cortical cultured neurons.The result demonstrated that Brahmi extract protected neurons from beta-amyloid-induced cell death,but not glutamate-induced excitotoxicity.The standardized extract of Brahmi is formulated as a film-coated tablet.The effect of Brahmi extract on learning and memory was studied in the middle aged and elderly volunteers.The results showed that Brahmi extract(300and 600mg·d-1)could improve quality of life in the elderly by improving the physical fitness via the increase in efficiency of postural balance.It also improved the psychological fitness by increasing alertness and attention resulted in the improvement of learning and memory.In addition,Brahmi extract could decrease depression-like symptom.The dosage used in this study did not produce toxic and side effects.CONCLUSION The in vitro and in vivo studies suggested that brahmi is a potential medicinal plant for memory enhancer.The clinical study showed that brahmi tablet could improve physical fitness and enhance memory in healthy volunteers.展开更多
文摘The development of new chiral stationary phases has been very important in the a ccurate analysis of drug enantiomers and their metabolites in biological samples during drug discovery and development. New chiral stationary phases have been d eveloped using conalbumin and flavoprotein from chicken egg whites, which have b een applied to a broad range of drug enantiomers. The application and characteri zation of these two chiral columns for high-performance liquid chromatograp hy have been documented. Both specific and non-specific interactions, based on the silica gel surface and linker moiety, influenced retention and chiral separa tion of solutes. Interactions between drug enantiomers and proteins, as a pseudo chiral stationary phase, were investigated with affinity capillary electrophore sis, in order to avoid the effects of non-specific interactions. The chiral dis crimination region for ketoprofen on the flavoprotein surface was concluded to c onsist of an α-helix structure. Studies with chemically modified flavoprot ein indicated that two types of interactions at the chiral discrimination region were required for chiral separation: a π-π interaction between a tryptophan residue and the aromatic ring of ketoprofen, and an ionic interaction between th e carboxyl group of ketoprofen and an amino and carboxyl group of the protein. I n the bod y, drugs and biologically active substances having a carboxyl group have been kn own to transform various metabolites such as acyl glucuronide. The acyl adenylat e has also been noted as a chemically active intermediate of coenzyme A ligation . Both the acyl adenylate and the acyl glucuronide produced protein adducts by r eacting with nucleophilic groups such as amino groups on protein molecules. To c haracterize both active intermediates and protein adducts, analytical techniques conferring highly selective molecular recognition, such as high-performance li quid chromatography and mass spectrometry, were required.
基金The project supported by National Research Council of Thailand(NRCT)
文摘OBJECTIVE Brahmi(Bacopa monnieri Wettst.,Schrophulariaceae)has been used in Ayuravedic medicine as a memory enhancer.We aimed at research and development of Brahmi for clinical use as the food supplement for memory improvement.METHODS The standardized extract of Brahmi has been developed.The neuroprotective effect of the extract was tested using in vitro and in vivo assay.A double-blinded randomized control trial of brahmi tablet was conducted in 60 middle-aged elderly volunteers.RESULTS The in vivo studies indicated that the standardized extract had neuroprotective effect at the doses of 40 and 80mg·kg-1.The escape latency time of rats in Morris water maze test was reduced.Moreover,the reduction of neurons and cholinergic neuron densities were mitigated.We also tested its protection effect against the beta-amyloid protein and glutamate-induced neurotoxicity in primary cortical cultured neurons.The result demonstrated that Brahmi extract protected neurons from beta-amyloid-induced cell death,but not glutamate-induced excitotoxicity.The standardized extract of Brahmi is formulated as a film-coated tablet.The effect of Brahmi extract on learning and memory was studied in the middle aged and elderly volunteers.The results showed that Brahmi extract(300and 600mg·d-1)could improve quality of life in the elderly by improving the physical fitness via the increase in efficiency of postural balance.It also improved the psychological fitness by increasing alertness and attention resulted in the improvement of learning and memory.In addition,Brahmi extract could decrease depression-like symptom.The dosage used in this study did not produce toxic and side effects.CONCLUSION The in vitro and in vivo studies suggested that brahmi is a potential medicinal plant for memory enhancer.The clinical study showed that brahmi tablet could improve physical fitness and enhance memory in healthy volunteers.
