OBJECTIVE:To study relative bioavailability of dauricine self-microemulsifying drug delivery system (SMEDDS) in rats. METHODS:12 rats were randomly divided into dauricine SMEDDS group (20 mg/kg) and dauricine solution group (50 mg/kg),6 rats in each group. They were given relevant medicine intragastrically. Then,0.3 ml plasma was collected from orbital venous plexus before medication and 0.167,0.333,0.5,0.75,1,2,4,8,12,24,36 h after medication. The plasma concentration of da- uricine was determined by HPLC-MS/MS,and DAS 3.0 was used to calculate pharmacokinetic parameters and evaluate the relative bioavailability of dauricine with dauricine SMEDDS. RESULTS:The linear range of dauricine in plasma were 2.12-424 ng/ml (r=0.999 9);RSDs of intra-day and inter-day were all lower than 10%. Pharmacokinetic parameters of dauricine solution and dau-ricine SMEDDS were that cmax were(126.3±37.4)ng/ml and(179.6±51.5)ng/ml;t1/2 were(11.48±4.58)and(21.79±6.59)h;AUC0-t were (1 963.5±638.3)ng·h/ml and(2 535.8±739.5)ng·h/ml;AUC0-∞ were(2 256.3±703.5)ng·h/ml and(2 854.6± 768.7)ng·h/ml,respectively. The relative bioavailability of dauricine SMEDDS were 323% and 316% by calculating with AUC0-t and AUC0-∞,respectively. CONCLUSIONS:Intragastric administration of dauricine SMEDDS can improve relative bioavailability of dauricine significantly.

Objective To observe the effect of muscone on the blood-brain barrier and neuropathological changes after complete cerebral ischemia/reperfusion of rats.Methods The global cerebral ischemia/reperfusion injury model was established by the four-vessel occlusion(4VO) method,and then the model animals were given high-,middle-and low-dose muscone.Meanwhile,sham-operation group,model group,and positive control group were also set up.The rats neuroethology behavior,and the contents of superoxide dismutase(SOD),malondialdehyde(MDA) and excitatory amino acid(EAA) in ischemic brain tissue were examined.Results Muscone increased SOD content,lowered MDA content,reduced the increase of EAA content caused by ischemia and hypoxia,and inhibited the excitatory neurotoxicity caused by EAA.Conclusion Muscone has obvious protective effect on rats with complete cerebral ischemia/reperfusion injury.

Objective To develop an HPLC method for the determination of chlorogenic acid in Xiao'er Yinniu Granula.Methods A Phenomenex ODS C18 column (4.6 mm?250 mm,5 ?m) was used,column temperature was at 20 ℃,methanol-0.4 %phosphoric acid water solution(20:80)was used as the mobile phase,the flow rate was 1 mL?min-1,and the detection wavelength was 327 nm.Results The calibration curve of chlorogenic acid was linear between 0.284～1.704 ?g (r=0.999 6),the average recovery and the relative standard deviation were 96.19 %and 1.16 %(n=5),respectively.Conclusion The method is simple,accurate and reproducible,by whihc chlorogenic acid can be better separated from Xiao'er Yinniu Granula.This method can be used for quality control of Xiao'er Yinniu Granula.

OBJECTIVETo study the time-toxicity and dose-toxicity relationships caused by multiple dose of total Bupleurum saponin extracts to rats.

METHODRats were picked according to different time or dose points, and total Bupleurum saponin crude extracts were administered to rats. The death circumstance and toxicity of mice were observed, ALT and AST in serum were detected. Indice of the liver, index was calculated. And the morphological changes of liver tissue were observed under light microscope.

RESULTThe "time-toxicity" relationship study showed that ALT and AST in rats' serum began to increase after 7 days' administration, and with obvious hepatotoxicity after 15 days', then there was concurrent toxicity and death. The "dose-toxicity" relationship study showed that compared with the control group, the total Bupleurum saponin crude extracts between 51. 2 and 125.0 g x kg(-1) dose could cause the obvious hepatotoxicity to rats in 15 days' administration, which was represented by that ALT and AST in serum increased significantly with the dose increased, the ratio of liver to body increased, and under light microscope, the different doses' liver tissue of mice all had edema in different degree and fatty degeneration in liver cells, and the high-dose and long time administration group appeared to be necrosis, lobular structure unclear. The above-mentioned change gradually aggravated with dose increasing, and obviously diversity compared with distilled water control group.

CONCLUSIONWith administrated a multiple dose and long time to rats, the total Bupleurum saponins crude extracts could cause serious liver injury and even death, and there were certain time-toxicity and dose-toxicity relationships.

Alanine Transaminase ; metabolism ; Animals ; Aspartate Aminotransferases ; metabolism ; Bupleurum ; chemistry ; Complex Mixtures ; administration & dosage ; toxicity ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Liver ; drug effects ; enzymology ; pathology ; Male ; Rats ; Rats, Wistar ; Saponins ; chemistry ; Time Factors ; Toxicity Tests ; methods

Objective To study the effect of maca extract on sport fatigue and its antioxidant effect.Methods 50 healthy male Wistar rats were randomly divided into control group (normal breeding,without swimming,equal amount of distilled water for gavage),simple swimming group (swimming,equal amount of distilled water for gavage),swimming and medicine group (divided into maca extract 4.0,8.0 and 16.0 g/(kg· bw) groups,respectively),10 rats in each group.All rats were freely swimming in the circulating water flow daily for 15 days.On the 16th day of experiment,liver tissue samples were collected.The liver lipid peroxide (LPO),superoxide dismutase (SOD),glutathione peroxidase (GSH-Px) and liver glycogen level were determined.Results When rats were administered with maca extract at the doses of 4.0,8.0,16.0 g/(kg· bw),respectively,the swimming time before sinking and the total swimming time were increased by 18.99%,64.46% and 90.69%,and 18.99%,56.23% and 94.72%,respectively,while the numbers of times of sinking were decreased by 27.44%,42.86%,64.11% (P<0.01),respectively,compared with the swimming rats without maca extract treatment.The LPO content in the liver of rats treated with maca extract 4.0,8.0,16.0 g/(kg· bw) were reduced by 31.31%,42.00% and 31.31%,respectively,while the levels of SOD,GSH-Px and liver glycogen were enhanced by 25.92%,31.82%,62.09%,12.33%,23.01%,46.36% and 17.83%,44.69%,62.99%,respectively,over those of rats without maca extract treatment.Conclusions Maca extract reduces the liver LPO level,increases liver glycogen level,improves the SOD and GSH-Px activity,therefore,plays a protective role in sport fatigue.

OBJECTIVETo explore the mechanism of glutamate (Glu)-induced PC12 cell apoptosis and the protective effect of muscone.

METHODPC12 cells were randomly divided into six groups: normal group (Normal), model group injured by glutamate (Glu), nimodipine group (Nim) and muskone groups (Mus) of high, middle and low doses. The PC12 cells were pretreated with or without different concentrations of muskone for 30 min and then exposed to glutamate. MTT assay for cell survival, flow cytometric detection of apoptotic cells, DCF assay for reactive oxygen species (ROS) and flow cytometric assay was performed to determine the mitochondrial membrane potential in PC12 cell.

RESULTPC12 cell damage, the concentrations of [Ca2+], and apoptosis induced by Glu were decreased after being administrated with paeoniflorin.

CONCLUSIONMuskone inhibited Glu-induced apoptosis in PC12 cells. The mechanism is related to inhibiting intracellular Ca2+ overload and maintaining mitochondral membrance potential.

Animals ; Apoptosis ; drug effects ; Calcium ; metabolism ; Cell Survival ; drug effects ; Cycloparaffins ; pharmacology ; Glutamic Acid ; pharmacology ; Membrane Potential, Mitochondrial ; drug effects ; PC12 Cells ; Pheochromocytoma ; metabolism ; physiopathology ; Protective Agents ; pharmacology ; Rats

Objective To investigate the factors of term pregnancy fetal distress at term pregnancy and intervention midwifery cesarean section and vaginal fetal distress. Methods All 104 cases of full-term pregnancy with maternal fetal distress in labor were random divided into observation group and control group from our hospital from October 2012-October 2013, each group had 52 cases. Mothers in the control group were given vaginal midwifery, maternal in the observation group were used cesarean section, fetal distress factors and maternal and neonatal outcomes of two groups were compared and analyzed. Results Fetal distress factor (placenta, umbilical cord factors, maternal factors, fetal factors or amniotic fluid, etc.) of two groups were compared, the difference was not statistically significant (P>0.05). The inci dence of postpartum hemorrhage, neonatal asphyxia, hypoxic ischemic encephalopathy, fetal growth restric-tion,puerperal infection and hypoproteinemia of the observation group were 5.77%,5.77%, 3.85%,1.92%, 11.54%,9.62%,compared with 9.62%, 7.69%, 5.77%, 1.92%, 7.69%, 5.77%in the control group,the difference was not statis-tically significant (P>0.05). Single factor factors Logistic regression analysis results showed that the umbilical cord and placenta, fetal and maternal,amniotic fluid dung are independent risk factors of fetal distress. Multiple factors Logistic regression analysis results showed that fetal and maternal,amniotic fluid dung are independent risk factors of fetal dis-tress. neonatal deaths of two groups did not occur. Conclusion Vaginal delivery applications and cesarean surgery in treatment of fetal distress of full-term pregnancy can get better maternal and neonatal outcomes, should be based on the specific circumstances of women to choose the appropriate mode of delivery.

OBJECTIVE：To study the anti-tumor effect of artemether （ARM）self-microemulsifying drug delivery system （SMEDDS） on human glioma subcutaneously transplanted model mice. METHODS ：Human glioma cell line SHG 44 was inoculated and passed on to establish subcutaneous transplanted tumor model of nude mice. At the 5th，10th，15th，20th and 25th day after inoculation ，the tumor tissue volume was measured and the growth curve was drawn to confirm the initial stage of rapid tumor proliferation. Thirty nude mice was collected to establish subeutaneously transplanted tumor nude model ，and then divided into control group （normal saline ），ARM suspension group [ 60 mg/（kg·d）]，ARM-SMEDDS low-dose ，medium-dose and high-dose groups [ 10，20，30 mg/（kg·d）] at the initial stage of rapid tumor proliferation. They were given normal saline and relevant solution intragastrically once a day ，for consecutive 30 d. The weight change and general sibuation of mice were recorded. The change of tumor volume was determined and relative tumor proliferation rate was calculated. RESULTS ：The subcutaneously transplanted tumor tissue entered the initial stage of rapid tumor proliferation from the 10th day after transplantation. The general situation was normal ，and there was no obvious abnormal reaction in mice of each group during treatment. Since 10th day of administration，tumor tissue volume of mice in ARM-SMEDDS groups were shortened significantly than control group （P＜0.05）. At 15th day of administration ，tumor volume of mice in ARM-SMEDDS groups were shortened significantly than ARM suspension group（P＜0.05）. After last administration ，relative tumor proliferation rates of mice in ARM-SMEDDS groups were decreased significantly，compared with ARM suspension group （P＜0.05）. CONCLUSIONS ：ARM-SMEDDS show significant inhibitory effect on the proliferation of human glioma ，and are better than suspension with higher dosage.