Total synthesis of natural product (R)-4-phenyl-2-O-[beta-D-xylopyranosyl(1-->6)-beta-D-glucopyranosyl]butane and its epimer.

The new compound (R)-4-phenyl-2-O-[beta-d-xylopyranosyl(1 --> 6)-beta-D-glucopyranosyl]butane (1) and its epimer (2), together with (R)-4-phenyl-2-O-beta-D-glucopyranosyl butane (24) and (S)-4-phenyl-2-O-beta-D-glucopyranosyl butane (25) were firstly synthesized from 4-phenylbutan-2-one and glucose. The absolute configuration of C-2 for 1 was confirmed as R. Their anti-tumour activities were evaluated.

Synthesis of three natural diosgenyl glycosides.

Three well-known natural diosgenyl glycosides which have the same sugar chains but different sequence, ophipogonin C', polyphillin C and prosapogenin B, were synthesised by a facile approach. A method using the levulinyl group as a protecting group to selectively mask the C3-OH of diosgenyl 4,6-O-benzylidene-beta-D-glucopyranoside is described.

Association study of polymorphisms in glycine transporter with schizophrenia.

Glycine acts as an obligatory co-agonist with glutamate on N-methyl-D-aspartate (NMDA) receptors. Brain glycine availability is determined by glycine transporters (GlyT1 or SLC6A9), which mediate glycine reuptake into nerve terminals. Since hypofunction of NMDA receptors has been implicated in the pathophysiology of schizophrenia, this study tests the hypothesis that GlyT1 genetic variants confer susceptibility to schizophrenia. Four GlyT1 polymorphisms were studied in a sample population of 249 people with schizophrenia and 210 normal controls. One polymorphism (rs16831541) was not informative in our Chinese population while the other three polymorphisms (rs1766967, rs2248632 and rs2248253) were analysed with chi-square tests and haplotype analysis. Significant linkage disequilibrium was obtained among the three polymorphisms. Neither single marker nor haplotype analysis revealed an association between variants at the GlyT1 locus and schizophrenia, suggesting that it is unlikely that the GlyT1 polymorphisms investigated play a substantial role in conferring susceptibility to schizophrenia in the Chinese population. Further studies with other GlyT1 variants, relating either to schizophrenia, psychotic symptoms or to therapeutic response in schizophrenia, are suggested.

Comparisons of different animal skins with human skin in drug percutaneous penetration studies.

The in vitro penetration of theophylline, sodium diclofenac and benzoic acid through artificial cellulose membrane and eight animal skins was investigated. The intact animal skins including stratum corneum (SC) and viable epidermis were taken from frog, snake with or without scales, nude mice, Sprague-Dawley rat, porcine and human prepuce and thigh skin. The results indicated that the penetration was fastest through cellulose membrane and frog skin and slowest through human prepuce and thigh skin. The snake skin with scales slowed down the penetration rate more significantly than the scaled skin. Benzoic acid was the fastest penetrant through all animal skins. The permeable behaviors of sodium diclofenac through SC and intact skin of snake, porcine and human were compared. In porcine, sodium diclofenac penetrated through SC at a rate 33 times higher than through intact skin, but in snake and human skin, the rate through SC was only 2.2 and 1.6 times higher than through intact ones. This implies that both viable epidermis and SC were the major rate limiting barriers in drug penetration. DSC thermograms and IR spectra showed that the SC of snake, porcine and human thigh were very similar in structure and components. The study suggests that snake skin, porcine skin and human prepuce skin could replace the human skin in in vitro drug penetration experiments.

Effect of traditional Chinese herbal medicines on the pharmacokinetics of western drugs in Sprague-Dawley rats of different ages (II): Aminophylline-huan shao tan and aminophylline-pu chung yi chi tang.

The effect of Chinese herbal medicines (Huan Shao Tan and Pu Chung Yi Chi Tang) and western drugs (sodium phenobarbital and cimetidine) on the serum concentration and pharmacokinetic parameters of theophylline and cytochrome P-450 of Sprague-Dawley (SD) rats of three different ages were examined. The older rats without pretreatment with Chinese herbal medicines and western drugs exhibited higher serum theophylline concentration and lower pharmacokinetic parameters of theophylline than middle-aged and younger rats (P < 0.05), but there was no difference in cytochrome P-450 activity among the three different ages of rats. All rats when pretreated with sodium phenobarbital showed lower serum theophylline concentration and higher pharmacokinetics parameters of theophylline. Also, the activity of cytochrome P-450 was higher (P < 0.05). When cimetidine was pre-administered in SD rats of three age groups, all rats exhibited lower serum theophylline concentration and higher pharmacokinetics parameters (P < 0.05), but the activity of cytochrome P-450 remained unchanged (P > 0.05). The results were opposite to other studies, probably because the dose and dosing intervals were different. No single effect occurred on the younger and middle-aged rats after pretreatment with Huan Shao Tan and Pu Chung Yi Chi Tang: their serum theophylline concentration, pharmacokinetics parameters and cytochrome P-450 activity were the same as the control group. However, the older rats after pretreatment with Huan Shao Tan or Pu Chung Yi Chi Tang showed lower serum theophylline concentration and higher pharmacokinetics parameters than the younger and middle-aged rats pretreated with similar Chinese herbal medicines. This indicates that Huan Shao Tan and Pu Chung Yi Chi Tang may perhaps improve the elimination of theophylline in older rats. This might be attributed to the increase in hepatic blood flow or in liver volume, since the activity of cytochrome P-450 was not affected by the administration of Chinese herbal medicines.

Effect of traditional Chinese herbal medicines on the pharmacokinetics of western drugs in SD rats of different ages. I. Aminophylline-Tin chuan Tang and aminophylline-Hsiao Ching Long Tang.

The effect of the traditional Chinese herbal medicines (Tin Chuan Tang and Hsiao Ching Long Tang) on the serum concentrations and pharmacokinetics of aminophylline was examined in three different ages of SD rats. Each traditional Chinese herbal medicine was orally preadministered to SD rats for one week and then aminophylline was administered intravenously. The serum concentrations and pharmacokinetic parameters of theophylline were estimated by a two-compartment open model. The liver isolated after the last blood sampling was homogenized and the activity of hepatic cytochrome p-450 was determined. Significant difference was found in some pharmacokinetic parameters of theophylline such as K10, t 1/2, Cl and Vd for three different ages of SD rats without pretreatment with Chinese herbal drugs (p less than 0.05). However, pretreatment with Tin Chuan Tang or Hsiao Ching Long Tang did not affect the pharmacokinetic parameters of theophylline in three different ages of SD rats (p greater than 0.05). We also found that there was no correlation between age and activity of cytochrome p-450 of SD rats (p greater than 0.05). The decline in some pharmacokinetic parameters of theophylline in the elderly rats perhaps might be attributed to the decrease in hepatic blood flow and liver volume. It is concluded that there was no drug interaction between theophylline and Tin Chuan Tang or Hsiao Ching Long Tang in the different ages of SD rats.