Metabonomics is a new branch of "-omics" science in post-gene time. The physiological and biochemical situation can be directly understood by its "metabolome profile" as a whole in metabonomics. Therefore it can provide a lot of information that differs from those came out of other "-omics". Metabonomics has been used to evaluate the test animal models and xenobiotics each producing a distinctive series of metabolic perturbations that are characteristic of the type of action mechanism, target organ of toxicity, and tissue damage. In research and development of new drugs, metabonomics is hopeful to be necessary part. Applying metabonomics involves metabolic databases for the use in discovery of new biomarkers, in screening of new drugs, in drug safety testing, and in action mechanism research. Metabonomics is also hopeful for modern research of Chinese materia medica.

OBJECTIVE： To prepare Yousaiqing suppository for treating ulcerative colitis and observe its clinical therapeutic effect.METHODS： The ingredients of suppository， PASA and berberine HCl， were determined with RP-HPLC and the therapeutic effect was observed in comparison with sulfasalazine suppository.RESULTS： This method of quality control was feasible and the effective rate for ulcerative colitis amounted to 70.7％ .CONCLUSION： The quality control method is simple， reliable and suitable to routine analysis and the therapeutic effect is satisfactory.

In this review, the author analyzed the challenges in modern research and development of Traditional Chinese Medicine (TCM) products. Chinese traditional and herb drugs have gained interest from the international medical, biomedical and pharmaceutical institutions as potential source of valuable medicinal agents. For the researches and development of TCMs, the first challenge is to evaluate the efficacy, pharmacological properties, action mechanism and active chemical constituents. The second one is to summarize the issues for developing safety research methodologies, to improve the quality and enhance the value of research in TCM and to provide appropriate evaluation methods to facilitate the regulation and registration of TCM products, and the third is to study drug metabolism and pharmacokinetics, and the fourth is to apply new "-omics" techniques and tools in new revolution in drug discovery-development and to impact on modern research of TCM products. This interest is needed to apply modern research on the development and exploration of the promising medical potential resources of Chinese traditional and herbal drugs, especially from medicinal plants.

ObjectiveTo compare quantitative proteomic analysis of bromotetrandrine (W198) which was a Class Ⅰ new antitumor drug in China and tetrandrine (Tet) in K562 cell line using 18O-labeling method.MethodsTo illustrate its mechanism,a shotgun quantitative proteomic strategy employing 2D LC-MS-MS and trypsin catalyzed 18O-labeling quantification was carried out in this study.Compared to normal chronic leukemia cell line K562 and K562 induced by Tet,the proteomic changes of K562 induced by W198 were investigated.In order to validate the quantitation by the 18O-labeling,the analysis was done on an equivalent sample composed of the same amount of labeled and unlabeled proteins from normally cultured cells to act as a reference to the comparative sample.ResultsA threshold of ± 2-fold change for deciding whether a protein concentration was changed was settled for the following experiments.Comparing the 105 identified soluble proteins' expression levels of the apoptosis starting up K562 cells after W198 induction with the normally cultured cells,16 proteins were found with significantly altered expression levels after W198 treatment.Eight proteins were up-expressed including HMGB2,peroxiredoxin-2,and eIF4A-I,etc.Eight proteins were down-expressed including TCP-1,GRP94,GST-π,and SFGHs,etc.Compared to K562 induced by Tet,eight proteins of K562 were found with significantly altered expression levels after W198 treatment.Five proteins were up-expressed including HSP 90-β and 40S ribosomal protein S15a,etc.Three proteins were down-expressed including phosphoglycerate kinase 1,isoform 5 of interleukin enhancer-binding factor 3,etc.ConclusionThe 18O-labeling MS-MS-based method is ideal as a discovery tool,but it is not suitable for validation using a large number of samples.Other more effective methods,such as Western blotting should be used for further validation of candidate cancer proteins discovered from 18O-labeling samples.In total,105 soluble proteins were discovered,and 16 proteins were found with significantly altered expression levels after W198 treatment.These repressed or activated proteins are the potential drug targets of W198,which may provide novel targets for future development ofbiomarkers for cancer therapy.

Objective To develop and validate a simple,rapid,sensitive,and reproducible HPLC method for determination of hyperoside in plasma of dogs and for the subsequent pharmacokinetic (PK) study.Methods An accurate and reproducible HPLC-UV method was developed and validated for the determination of hyperoside in plasma of dogs,using kaempferol as internal standard.The plasma samples of dogs following ig administration of hyperoside were analyzed for the detection of quercetin after enzymatic hydrolysis treatment with combined β-glucuronidase and sulphatase.The analytes were separated on a Diamonsil C18 column (250 mm × 4.6 mm,5 μm).The mobile phase consisted of methanol-buffer solution (0.1mol/L NH4Ac + 0.3 mmol/L EDTA-Na2)-acetic acid (60:40:1) and was delivered at a flow rate of 1mL/min.The UV detector was set at 370 nm and the column temperature was maintained at 35 ℃.The sample injection volume was 20 μL.Data were collected and analyzed using the ANASTAR software.PK parameters were calculated with DAS software (2.0).Results Linear relationships were validated over the range of 0.01-1μg/mL for hyperoside (r =0.9997).The intra-and inter-day precision values for all samples were within 10.0％,and the accuracies of intra-and inter-day assays were within the range of 92.4％-102.4％.The validated method was successfully used to determine the hyperoside concentration in plasma of dogs for up to 12 h,after a single ig administration (25 mg/kg).The mean PK parameters for male and female dogs were as follows:Cmax (0.18 ± 0.05) and (0.16 ± 0.05) μg/mL,AUC0-∞ (0.79 ± 0.34) and (0.86 ± 0.27) μg/(mL·h),t1/2(ka) (0.89 ± 0.41) and (0.88 ± 0.28) h,respectively.Statistical analysis on the PK of hyperoside in male and female groups showed that sex had no significant impact on the PK of hyperoside (P ＞ 0.05).Conclusion The method is able and sufficient to be used in drug PK studies of hyperoside.

Transporters are membrane proteins mediating permeation of organic and inorganic solutes through the plasma membrane and membranes of intracellular organella.They play essential roles in the epithelial absorption and cellular uptake of nutrients as well as absorption,distribution,metabolism,and excretion of drugs.Because transporters contribute to determining the distribution of compounds in the body in concert with metabolic/synthetic enzymes,the drugs that affect the functions of transporters are expected to alter the distribution of compounds in the body and to ameliorate disrupted homeostasis.In this context,drugs targeting transporters have been used clinically.Such drugs include antidepressants targeting monoamine transporters,diuretics targeting inorganic ion transporters of renal tubules,and uricosuric agents targeting renal urate transporters.Now new transporter-targeting drugs designed based on post-genome drug development strategy have been in the process of clinical trials or basic/clinical researches.For example,the inhibitors of renal Na<'+>/glucose cotransporter SGLT2 have been proved for their efficacy in the treatment of diabetes mellitus.The cancer L-type amino acid transporter 1(LAT1)has been considered as a target of cancer diagnosis and therapeutics.The transporter-targeting drugs are expected to provide new rationale in the therapeutics of various diseases.

Gender-related differences in drug pharmacokinetics have frequently been considered as potentially important determinants for the clinical effectiveness of drug therapy. Major molecular factors involved in drug disposition include drug-metabolising enzymes and drug transporters. Oxidative drug metabolism by cytochrome P450 (CYP) enzymes is a major pathway for drug elimination. CYP3A4,the major human drug-metabolizing CYP enzymes,has repeatedly been suggested higher metabolic activity in women than that in men,which sex-dependent secretory patterns of growth hormone that may be responsible for.

brain and fatty. The accumulation excretion ratios within 96 h were 70.16% in urine and only 1.35% in feces after iv administration in rats, while within 24 h was 3.46% in bile. Conclusion The results of pharmacokinetics of novel r-hirudin in rats given by iv determined by RA are different from those determined by TCA-RA, but the trends indicated by the two methods are the same; urine excretion is the major excretion pathway.

AIM: To study the antiallerergic effects of norastemizole. METHODS: Antiallergic effects of norastemizole were study using rats and guinea pigs. RESULTS: Norastemizole(10 -9 -10 -8 mol?L -1 ) caused inhibition effect on the hisitamine induced contraction of isolated guinea pig ileum. Its IC 50 was 4.42 ?10 -9 mol?L -1 Norastemizole at oral doses of 0.1 , 0.5 , 1 mg?kg -1 , norastemizole caused a significant inhibition on the histamin phosphate induced shock in guinea pigs (P

The present study was to estimate pharmacokinetic parameters of metformin hydrochloride in 20 Chinese healthy volunteers with a limited sampling strategy (LSS), which will provide scientific data for bioequivalence and clinical application. A single dose of metformin was administrated to 20 healthy volunteers. The concentration of metformin in whole blood was determined by validated high performance liquid chromatography (HPLC) method. Multi-linear regression analysis was performed to establish a model to estimate AUC(0-24 h) and Cmax of metformin by LSS method. The LSS models were validated by the Jackknife method. The result indicated: the linearity relationship between AUC(0-24 h) or Cmax and single concentration point was poor. Several models for metformin AUC(0-24 h) or Cmax, estimation were better (r2 > 0.9, P < 0.05). Validation tests indicated that most informative sampling points (C2, C6 for AUC(0-24 h), C1.5, C2 for Cmax) provided accurate estimations of these parameters. So, a multi-linear regression model for estimation pharmacokinetic parameters of metformin by using LSS method is feasible.