Preventive effects of Rhizoma Coptidis and Atractylodes on mice with gastric-ulcer / 中南大学学报(医学版)

OBJECTIVES@#To detemine preventive effects of compound formula Rhizoma Coptidis and Atractylodes on mice with gastric-ulcer.@*METHODS@#The mice were randomly divided into a normal group, a gastric ulcer group, a ranitidine positive drug group, a Rhizoma Coptidis group, an Atractylodes group, and a Rhizoma Coptidis plus Atractylodes group (the ratios of Coptidis to Atractylodes were 9꞉1, 8꞉2, 7꞉3, 6꞉4, 5꞉5, or 4꞉6, respectively). Gastric ulcer models were established by intragastric administration of anhydrous ethanol after 6 days of preventive infusion. The mice were killed 6 days after the treatments. The whole stomach was opened to observe gross morphology of gastric mucosa. The pathological changes of gastric tissue were observed under microscope, and serum samples were collected to detect the contents of superoxide dimutase (SOD), malondialdehyde (MDA), NO, and endothelin-1 (ET-1).@*RESULTS@#The Rhizoma Coptidis and Atractylodes decoction significantly decreased ulcer area (<0.001), and the effects of compound formula are better than those of Coptidis and Atractylodes alone (<0.05, <0.01, or <0.001). The anti-ulcer effect of compound formula (Coptidis꞉Atractylodes=6꞉4) was the best one, and the anti-gastric ulcer effect of the high-dose group was significantly better than that of the ranitidine-positive group (<0.001). The ranitidine positive drug group, the high-dose group of Rhizoma Coptidis, the high-dose group of Atractylodes, and the high-dose group of Rhizoma Coptidis-Atractylodes (6꞉4) significantly reduced MDA, ET-1 (<0.01 or <0.001), and significantly increased SOD, NO in serum (<0.01 or <0.001).@*CONCLUSIONS@#Rhizoma Coptidis and Atractylodes decoction exerts the effect on preventing ethanol-induced gastric ulcer in mice in a ratio-dependent and dose-dependent manner. The mechanism might be related to anti-oxidation and relaxion of blood vessels. The combination of the two drugs shows a synergistic effect.

Study on Improvement Effects of Fingolimod on MCAO/R Injury Model Rats / 中国药房

OBJECTIVE： To observe improvement effects of fingolimod on middle cerebral artery occlusion/reperfusion （MCAO/R） injury model rats. METHODS： Male SD rats were randomly divided into sham operation group， model group and fingolimod low-dose， medium-dose and high-dose groups （0.5， 1， 2 mg/kg）， with 8 rats in each group. Except for sham operation group， MCAO/R injury model was induced by suture-occluded method in other groups. Administration groups were given relevant medicine intragastrically after reperfusion [1 h after reperfusion （1st day）， 22.5 h after reperfusion （2nd day）， and then every 24 h until 142.5 h of reperfusion （7th day）]. Sham operation group and model group were given constant volume of normal saline intragastrically， once a day， for consecutive 7 d. The scores of neurological deficit and balance beam test， the times of memory error [work memory error （WME）， reference memory error （RME） and total error] were recorded in each group. The contents of serum inflammatory cytokines （IL-6， IL-8， IL-10， TNF-α） were determined by ELISA， and triphenyl tetrazolium chloride staining method was used to detect the rate of cerebral infarction. RESULTS： Compared with sham operation group， neurological deficit scores （at different time points of 1st-7th day after administration）， balance beam test scores （2nd， 4th， 7th day after administration）， times of memory error （2nd， 4th， 7th day after administration）， the contents of serum inflammatory cytokines and the rate of cerebral infarction were increased significantly in model group （P＜0.05 or P＜0.01）. Compared with model group， neurological deficit scores （low-dose group at different time points of 3rd-7th day， medium-dose and high-dose groups at different time points of 2nd-7th day after administration）， balance beam test scores （low-dose group at 7th day， medium-dose group at 4th and 7th day， high-dose group at 2nd， 4th， 7th day）， RME times and total error times （low-dose group at 4th and 7th day， medium-dose group and high-dose group at 2nd， 4th， 7th day after administration）， WME times （administrations groups at 7th day after administration）， serum contents of IL-6， IL-8 and IL-10 （administrations groups）， serum contents of TNF-α （medium-dose and high-does groups） and cerebral infarction rate （medium-dose and high-dose groups） were all decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： Intragastric administration of fingolimod can significantly reduce neurological deficit score， balance beam test score and the times of memory error in MCAO/R injury model rats， and has a protective effect on cerebral tissue and memory function. These effects may be related to the down-regulation of inflammatory cytokines such as IL-6 and TNF-α by fingolimod.

Comparison of Ulcerative Colitis Models Respectively Induced by Free Drinking and Intragastric Administration of Dextran Sodium Sulfate in Mice / 中国药师

Objective:To investigate the differences in related indices of ulcerative colitis (UC) respectively induced by free drinking and intragastric administration of dextran sodium sulfate (DSS) in mice to provide experimental reference for the optimization of UC model.Methods:Totally 30 C57BL/6 mice were randomly divided into the normal control group,free drinking group and intragastric administration group with 10 ones in each.The mice drank water freely with free drinking or intragastric administration of 3% DSS solution at the dose of 4 g·kg-1·day-1 for 7 days to establish the UC model.The differences in disease activity index (DAI),histological damage sore and activity of myeloperoxidase (MPO) among the groups were compared.Results:Two mice died during the experiment in the free drinking group,and DAI of survival mice was (8.8±1.6).There was no death of mice in intragastric administration group,and DAI was (9.0±0.8),and there was no significant difference in DAI between the groups (P>0.05),while the coefficient of variation in the free drinking group was higher than that in the intragastric administration group (18.7 vs 8.6).The colonic histological damage score of the free drinking group and the intragastric administration group was 24.8±4.2 and 27.0±2.8,respectively,which was typical inflammatory change with no significant difference (P>0.05),while the coefficient of variation of the free drinking group was higher than that of the intragastric administration group (16.9 vs 10.4).MPO of the normal control group,free drinking group and intragastric administration group was (0.41±0.03),(2.32±0.34) and (2.05±0.18) U·g-1,respectively.Compared with the normal control group,significant difference in MPO was shown in the free drinking group and the intragastric administration group (P0.05),and the coefficient of variation in the free drinking group was higher than that in the intragastric administration group (14.7 vs 8.8).Conclusion:Both free drinking and intragastric administration of DSS can successfully induce the UC model in mice.Compared with the free drinking group,the intragastric administration group has low mortality rate and low coefficient of variation.Therefore,intragastric administration has more advantages than free drinking in inducing the UC model in mice.

Study on the Bioavailability Improvement of Dauricine Self-microemulsifying Drug Delivery System in Rats / 中国药房

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.

Distribution of Levofloxacin in Lung Tissue of Mice after Intragastric and Intravenous Administration of Tanreqing Injection Combined with Levofloxacin / 中国药房

OBJECTIVE:To compare the distribution of levofloxacin in lung of mice after intragastric and intravenous adminis-tration of Tanreqing injection combined with levofloxacin. METHODS:144 mice were randomly divided into experimental group and control group,with 72 mice in each group. Both groups were given Tanreqing injection(0.8 ml/kg). 1 h later,control group was given Levofloxacin injection(80 mg/kg)intravenously,and experimental group Levofloxacin tablet solution(80 mg/kg)intra-gastrically;every 8 mice were sacrificed for lung tissue collection at the time points of 0.05,0.083,0.17,0.5,1.0,2.0,4.0,8.0, 12.0 h and 0.083,0.17,0.33,0.5,1.0,2.0,4.0,8.0,12.0 h,respectively. Using ciprofloxacin as internal standard,the content of levofloxacin in lung tissue was determined by HPLC,and pharmacokinetic parameters were calculated by 3p97 program. RE-SULTS:The concentration-time curves of levofloxacin in lung tissue were in line with two-compartment model in 2 groups. The main pharmacokinetics of experimental group and control group were as follows as t1/2β of(4.17±0.84)h and(4.10±0.55)h;CL of(0.66±0.049)L/h and(0.71±0.21)L/h;AUC0-t of(109.48±12.34)mg·h/kg and(113.04±29.43)mg·h/kg;cmax of(38.76± 1.62) mg/kg and (42.28 ± 2.03) mg/kg,respectively. There was no statistical significance (P>0.05). Absolute bioavailability of levofloxacin was(96.85±17.39)% in experimental group with intragastric administration. CONCLUSIONS:After intravenous injec-tion of Tanreqing injection,the distribution of levofloxacin in lung tissue of mice are similiar between intragastric administration and intragastric administration.

The amphiphilic curcumin derivative attenuates liver fibrosis by anti-inflammatory and antioxidant effect / 中国药理学通报

Aim To investigate the effects of anti-in-flammation and antioxidation of an amphiphilic curcu-min derivative (Curc-OEG)on CCl4-induced hepatic fibrosis in rats.Methods Rats were randomly divided into four groups:control group,model group,curcumin and Curc-OEG treatment group.All rats except those in control group were given subcuta-neous injection of CCl4 and olive oil mixture,twice a week for 8 weeks.After 4 weeks,rats of control and model group were trea-ted with normal saline intravenously,curcumin group were ad-ministered with curcumin 400 mg.kg -1 .d -1 by gavage and Curc-OEG group were treated with Curc-OEG 1 00 mg.kg -1 .d -1 intra-venously respectively.After 4 weeks treatment,the serum levels of ALT and AST were tested.HE and Sirus staining were used to evaluate the extent of liver inflammation and fibrosis.The mRNA expression levels of proinflammatory cytokines of NF-kB,IL-1 β, IL-6,TNF-α,COX-2 were observed with Real Time PCR.The level of MOD,SOD and GSH in liver of rats were quantified. Results The levels of ALT in control,model,curcumin and Curc-OEG group was (31 .7 ±8.7)U·L -1 ,(383.0 ±75.6) U·L -1 ,(406.3 ±204.7)U·L -1 ,(1 07.0 ±73.7)U·L -1 respectively;that of AST was (1 37.7 ±32.7)U·L -1 ,(585.3 ±36.7)U·L -1 ,(485.0 ±246.5)U·L -1 ,(202.7 ±56.0) U·L -1 respectively,Curc-OEG possessed more hepatoprotective effects than that of curcumin.Liver pathology showed Curc-OEG treatment could significantly alleviate steatosis,reduce inflamma-tion and apparently suppress hepatic fibrogenesis by reducing the thickness of bridging fibrotic septa.Compared with curcumin, Curc-OEG down-regulated mRNA and protein expression levels of NF-kB,IL-1 β,IL-6,TNF-α,COX-2 (P <0.05 ).Moreo-ver,Curc-OEG reduced the level of MOD and increased the lev-els of SOD and GSH.Conclusion Curc-OEG could more sig-nificantly protect the rat liver from CCl4-caused fibrogenesis by anti-inflammatory and antioxidant effect than curcumin.

Therapeutic effect evaluation on the treatment of acute upper gastrointestinal bleeding with freezing Zidi mixture lavage / 国际中医中药杂志

Objective To observe the clinical effects of treating acute upper gastrointestinal bleeding(AUGIB) with freezing Zidi mixture lavage. Method 183 UGIB patients from the First Affiliated Hospital to Guanzhou University of TCM in August 2013 were randomly recruited into a control group with 91cases and a treatment group with 92 cases. The treatment group was treated with intragastric administration of freezing Zidi mixture, while the control group was treated with intragastric administration of cryohydrate and norepinephrine. The changes of clinical effects, blood pressure, hemoglobin, blood urea nitrogen, pulse and dark stool were observed and the bad emotions as anxiety, depression and fear were evaluated. Results ① On therapeutic effect, the total effective rate was 96.7% and 85.7% in the treatment group and the control group respectively, with statistical difference(χ2=2.943,P0.05). ④ On changes of anxiety, depression and fear:the treatment group [the(42.5±9.4), (41.6±9.7), (26.3±5.4)for each]was obviously improved after the treatment than the control group[the score was(51.2±10.1),(50.4±11.5),(30.4±6.9)for each],P<0.05. Conclusion Freezing Zidi mixture lavage can obviously elevate systolic pressure, decrease heart rate, enhance hemoglobin, decrease blood urea nitrogen, relieve body stress reaction and other clinical symptoms. Its effects were better than intragastric administration of cryohydrate and norepinephrine in treating AUGIB.

Acute Toxicity Test of Baicalin Capsule in Mice / 医学研究杂志

Objective To observe the acute toxic reaction and death of mice one day after intragastric administration of Baicalin capsule so as to appraise its safety. Methods The ICR mice were intragastrically administered with Baicalin powder in capsule at maximum concentration. There was no death of mice found and no LD_ 50 detected after administration. Hence the maximum dosage was identified. Results The maximum dosage of Baicalin powder is 15g/kg. Conclusions The Baicalin capsule is relatively safe.

Pharmacokinetics of Caffeic Acid in Rats / 中国药房

OBJECTIVE: To establish a HPLC method for the determination of serum concentration of caffeic acid in rats and which was applied to the pharmacokinetic study of caffeic acid. METHODS: The concentrations of caffeic acid in rats were determined after intragastric (ig) administration or intravenous (iv) administration of 50 mg?kg-1 caffeic acid and the pharmacokinetic parameters of caffeic acid analyzed by Topfit 2.0. RESULTS: The main pharmacokinetic parameters of caffeic acid after ig administration of caffeic acid were as follows: Cmax: (0.56?0.12) ?g?mL-1; tmax: (0.18?0.04) h; t1/2: (0.67?0.12) h; ke: (1.05?0.20) h-1; AUC(0～t): (0.34?0.05) ?g?h?mL-1. The main pharmacokinetic parameters of caffeic acid via iv administration were as follows: t1/2: (0.45?0.05) h; ke: (1.55?0.18) h-1; AUC(0～t): (9.07?2.24) ?g?h?mL-1. CONCLUSION: Administered intragastrically, caffeic acid was characterized by rapid absorption, short elimination half life (t1/2) and low absolute bioavailability in rats.

Protective effect of bivalent anti-snake venom IgY administered intragastrically on mice with cobra or viper envenomation / 中国病理生理杂志

AIM:The different effect of bivalent immunoglobulin Yolk(IgY) was evaluated against snake venom between intragastric administration and intraperitoneal injection in mice with cobra or viper envenomation.METHODS:The venom of naja and viper was injected alternately into the leghorn hen.Bivalent anti-snake venom IgY was extracted by water dilution.The concentration of bivalent IgY in plasma was observed in indirect ELISA assay after bivalent anti-snake venom IgY taken orally.The gastric emptying function test was used for determining optimization time after gastric administration of IgY.The protective effect of bivalent anti-snake venom IgY was compared between intragastric administration and intraperitoneal injection in mice with cobra or viper envenomation.RESULTS:Bivalent anti-snake venom IgY was extracted from eggs laid in 28-42 d after the first immunization.The titers of Bivalent IgY against cobra and viper venom were 1:12 800 and 1:6 400.At the time of 2.5-3.5 h after bivalent anti-snake venom IgY was taken orally in three concentrations(75 mg,150 mg,300 mg?0.5 mL-1?20 g-1 BW),the gastric evacuation rate of mice was above 68.9%,with the plasma concentration of bivalent IgY in peak.The survival time of mice envenomation with snake venom was extremely prolonged(P

Location of mycobacterium tuberculosis and induction on cellular immunity after intragastric administration of BCG in mice / 中国免疫学杂志

Objective:To determine the location of mycobacterium tuberculosis(MTB) and whether the cellular immunity is induced after intragastric administration of BCG in mice.Methods:Viable MTB were detected in mesenteric lymph nodes?spleen and lungs at day 15,30 and 60 after intragastric administration of BCG to mice.The proliferation of T-lymphocyte with the stimulus of the purified protein derivative(PPD) was measured at day 60 and 90 after intragastric administration of BCG to mice.The expression of interleukin-2(IL-2) of T-lymphocyte in spleen was detected at day 60 and 90 after intragastric administration of BCG.Results:Viable MTB were detected in the mesenteric lymph nodes and spleen at day 15,30 and 60 after intragastric administration.At day 60 and 90 after intragastric administration of BCG to mice,the ratio of T-lymphocyte proliferation was 31.32%,37.94% separately and the production of IL-2 was 37.47?5.60 U/ml,39.41?7.73 U/ml separately.There were no statistically significant differences in the cellular immunity between the mice of the intragastric administration of BCG significant differences in the cellular immunity between the mice of the intragastric administration and the mice of the subcutaneous vaccination of BCG( P 0.05).Conclusion:Intragastric administration of BCG can induce cellular immunity in mice.