Objective To estabhsh a set of consummate evaluation methods of animal models which are with syndromes of Traditional Chinese Medicine.Methods By means of Streptococcus pneumoniae-induced pyretic pulmonary syndrome model for the entry point,in the base of the conventional evaluation methods,further attempt were made through metabonomies,through analyzing metabolic fingerprint data of rats'urine in the control group together with the model group and metabolome of rats'urine in model group at different times,in order to approach the evaluation methods of animal models.Results After rats were given Streptococctts pneumoniae through nose,compared with the control group,both the body temperature variance and lencocyte count in model group were statistically significant with P <0.01,pathological changes of lung was obvious;According to the metabolic results,metabolic profiles of rats'urine in model group changed and metabolome diverged obviously in scores plot,the research results of metabonomics were coincide with the results of macroscopy physical sign and pathological biochemistry of Pyrefic pulmonary syndrome.Conclusion Metabonomics can be used to evaluate the studies of animal models with syndromes of traditional Chinese medieine.

Objecave To develop a sensitive and specific LC-MS/MS method for determination of testolactone in human urine.Methods A C_(18 )column(2.1×50mm,3.5μm) was used.The mobile phase Was a mixture of acetonitrile and the buffer solution(ammonium acetate-water solution adjusted with formic acid to pH 3.5)at a flow rate of 0.5ml/min.A mass spectrometer equipped with electrospray ionization source was used as a detector and operated in the positive mode.In multiple reaction monitoring(MRM)mode,the ion transitions of m/z 301→121 and m/z 301→25 was used to qualify and quantify the testolactone,respectively.Results Chromatograms showed no endogenous interfering peaks with the urine blank sample.Each analysis was completed within 7min The calibration wag linear in the concentration range within 0.1～50μg/ml.The intra-batch and inter-batch RSD were less than 10%.The recovery rate of the extraction was about 60%.Conclusions The method is proved to meet the requirements of WADA and be suitable for routine screening.

Aim To establish a set of consummate evaluation methods of animal models which are with syndromes of traditional Chinese medicine.Method By means of 2,4-dinitrophenol-induced fever syndrome model for the entry point,making use of meta bonomics as the platform,through analyzing metabolic fingerprint data of rat urine in the control and model group and metabolome of rat urine in model group at different time intervals,to approach the evaluation methods of animal models.Results Through research by metabonomics,the results showed that 2,4-dinitrophenol-induced animal models consisted with clinical fever syndrome of traditional Chinese medicine.Conclusion Metabonomics can be used for evaluation studies of animal models which are with syndromes of traditional Chinese medicine.

Objective To optimize the prescription ofBaichanting Tablets by the central composite design-response surface methodology.Methods The doses of MCC, cCMC-Na, SiO2, and magnesium stearate were set as investigation factors; disintegration time and moisture rate were set as indexes. Linear equation quadratic polynomial described mathematic relationship of disintegration time and moisture rate with other four influence factors. Response surface was described according to the optimal mathematic models; the optimal prescription was chosen; predictive analysis was conducted.ResultsThe relationship of disintegration time and moisture rate with other four influence factors could not be described by linear equation. When quadratic polynomial matching was used, correlation coefficients were 0.837 9 and 0.923 1, with relatively high reliability. Optimal prescription contained 30.6%MCC, 10%cCMC-Na, 0.30%SiO2, and 0.10% magnesium stearate. The theoretical value and predicted value deviations of the disintegration time limit and moisture absorption rate were within 5%.Conclusion The predictability of the established model is good. Application of central composite design-response surface methodology can precisely optimize the prescription ofBaichanting Tablets.

In recent years, with the rapid development of Chinese materia medica (CMM) industry, its clinical applications have become more and more widespread. While, adverse reactions of CMM have also become increasingly prominent. However, for adverse reactions of some CMM, the applications of conventional toxicology studies cannot draw definitive conclusions. These CMM, which were not defined as toxic drugs in traditional Chinese medicine (TCM) theories, have unknown potential toxicities and affect the safety in their clinical use. This paper reviewed recent advances in studies on potential toxicity of non-toxic CMM. It analyzed and summarized potential toxic compounds among them, and introduced application for metabolomics researches on potential toxicities in non-toxic CMM.

ObjectiveTo study the neuron protection mechanism of Uncariae Ramulus Cum Uncis extract for the MPTP-induced PD mice.MethodsC57BL/6 mice were randomly divided into control group, model group, Uncariae Ramulus Cum Uncis extract group and madopar group, and injected with MPTP in abdominal cavity. Behavior test was used to detect grabbing capacity and body movement coordination capacity: three biochemical indexes (SOD, MDA, GSH-Px) were detected by biochemical process and the activity of two immune enzyme-linked indexes (IL-1β, IL-6) were detected by enzymelinked immunosorbent assay.ResultsCompared with the control group, the autonomic activity numbers of mice increased and climbing pole time decreased in the model group (P<0.05), enzymatic activity of SOD and GSH-Px decreased significantly and the contents of MDA, IL-1β and IL-6 increased obviously (P<0.01). Compared with model group, the autonomic activity numbers of mice increased and climbing pole time decreased in the Uncariae Ramulus Cum Uncis extract group and madopar group (P<0.05). Enzymatic activity of SOD and GSH-Px increased and the contents of MDA and IL-1β and IL-6 decreased (P<0.05,P<0.01).ConclusionUncariae Ramulus Cum Uncis extract can reduce neuronic apoptosis PD mice, whose therapeutic action may be realized through eliminating oxygen free radicals, improving oxidation resistance and reducing inflammatory reactions.

Objective To evaluate the efficacy of double filtration plasmapheresis (DFPP) combined with immunosuppressive agents (leflunomide plus methotrexate) on synovitis in magnetic resonance imaging (MRI) in patients with high active rheumatoid arthritis (RA). Methods Fifty eight patients with RA (disease duration 6 months to 12 years) were randomly divided. Thirty-one were randomized to the treatment group and 27 were randomized to the control group. All patients received leflunomide 10 mg, two times daily; plus methotrexate 15 mg orally once weekly. DFPP was performed in the treatment group once 1-2 weeks for 3-4 sessions. Control patients did not receive DFPP. All patients underwent contrast-enhanced MRI of the right wrist at the baseline and 6 months, 1 month in the treatment group. The signs including synovitis pannus, bone marrow edema and effusion were observed on MRI. The scoring of synovial hypertrophy, pannus, bone marrow edema were measured according to the outcome measures in RA MRI scoring system. Comparisons between groups were performed with paired-samples t test and independent-sample t test. Results The MRI synovitis score, MRI pannus score and MRI bone marrow edema in the treatment group was (1.4±1.6), (0.13± 0.35) and (5±4) respectively,so was significantly lower than that of the control group [respectively for (7.9± 1.3), (2.76±0.43), (16±12),P<0.01]. 53% of the treatment group satisfied both the disease activity score 28-joint assessment and MRI synovitis assessment (no enhancement of synovium or pannus, no effusion), but none in the control group (P<0.01). Significant changes at 1 month was observed in DAS28 and HAQ scores (P<0.01), but not in the MRI synovitis score, MRI pannus score, MRI bone marrow edema score and effusion in the treatment group (P>0.05). Conclusion DFPP combined with immunosuppressive agents can significantly improve synovitis in MRI in patients with high active RA. Improvement of the signs of MRI is later than that in the clinic. So imaging assessment may be necessary for accurate evaluation of disease status and selection of therapy.

RNA interference(RNAi)is a process by which introduced small interfering RNA(siRNA)can cause the specific degradation of mRNA with identical sequences. The human herpes simplex virus type 1(HSV-1)RR is composed of two distinct homodimeric subunits encoded by UL39 and UL40, respectively. In this study, we applied siRNAs targeting the UL39 and UL40 genes of HSV-1. We showed that synthetic siRNA silenced effectively and specifically UL39 and UL40 mRNA expression and inhibited HSV-1 replication. Our work offers new possibilities for RNAi as a genetic tool for inhibition of HSV-1 replication.

OBJECTIVETo analyze isofraxidin and its metabolites in rat plasma, bile, urine and feces after the oral administration of A. senticosus extracts.

METHODAfter the oral administration of 325 mg x kg(-1) of A. senticosus extracts, rat blood samples were collected at 1, 1.5, 2, 4, 6 h and bile samples were collected during 0-12 h. The above samples were prepared by SPE. Their urine and feces samples were collected during 0-12 h and 12-24 h. These samples were analyzed by UPLC-Q-TOF-MS and processed using Metabolynx XS.

RESULTM0 was detected in rat plasma, bile, urine and feces, isofraxidin glucuronide (M1) was detected in rat plasma and bile, which was first reported as the metabolite of isofraxidin.

CONCLUSIONIsofraxidin can be metabolized in the form of glucuronidation in vivo and evacuated in the form of isofraxidin.

Animals ; Chromatography, High Pressure Liquid ; Coumarins ; blood ; metabolism ; pharmacokinetics ; Drugs, Chinese Herbal ; metabolism ; pharmacokinetics ; Eleutherococcus ; chemistry ; Male ; Mass Spectrometry ; Rats ; Rats, Wistar ; Statistics as Topic

OBJECTIVEMetabonomics researches of Scutellariae Radix interfering pyretic pulmonary syndrome had been done, to determine the specific biomarkers of pyretic pulmonary syndrome, and to approach the mechanism that Scutellariae Radix interfered the variation of these biomarkers.

METHODMetabonomics technique, UPLC-Q-TOF/MS analytical means and PCA statistical methods were utilized to investigate the trajectory change and inter-relationship of urinary metabolome of rats treated differently.

RESULTSix specific biomarkers were determined which could represent Streptococcus pneumoniae-induced pyretic pulmonary syndrome in rats. Scutellariae Radix could significantly adjust the ascended biomarkers to the normal level. Meanwhile two of these biomarkers were identified as Delta-12-prostaglandin J2 and indoxyl sulfate.

CONCLUSIONThere was a good therapeutic function of Scutellariae Radix on pyretic pulmonary syndrome, which was elucidated on the metabolic aspects. There was also a correlationship between the mechanism of Scutellariae Radix curing pyretic pulmonary syndrome and the six specific biomarkers.

Animals ; Drugs, Chinese Herbal ; therapeutic use ; Lung Diseases ; drug therapy ; metabolism ; Male ; Pneumococcal Infections ; drug therapy ; metabolism ; Rats ; Rats, Wistar ; Scutellaria baicalensis ; chemistry