Using bioactive compounds 7-hydroxy flavone, salicylaldehyde, cinnamic acid and 4-amino-5- mercapto-1,2,4-triazoles as starting materials, three new types of flavone derivatives containing 1,2,4-triazole structure were synthesized via different step reactions. These new compounds were characterized by 1IHNMR, ESI-MS, IR and elemental analysis. Their scavenging effects on the superoxide radical (O2·-), hydroxyl radical (·OH), DPPH · radical and their total reduction activities were tested. The results showed that all of the compounds possessed some antioxidative activity at the concentration of 0.5 mg · mL(-1), but the scavenging ability of the target compounds was lower than that of the standard compound Vc.
Cinnamates ; chemistry ; Flavones ; chemical synthesis ; chemistry ; Flavonoids ; chemistry ; Free Radical Scavengers ; chemical synthesis ; chemistry ; Triazoles ; chemistry

OBJECTIVETo observe the clinical effect of Ziyin Huoxue Granule (ZHG) combined glucocorticoids and antibiotics in treatment of radiation pneumonitis.

METHODSTotally 70 radiation pneumonitis patients were assigned to the treatment group and the control group according to random digit table, 35 in each group. All patients received glucocorticoids and antibiotics. Patients in the treatment group additionally took ZHG, one dose per day for 4 successive weeks. Watters clinical-radiologic-physiologic (CRP) score, Karnofsky Performance Status Scale (KPS) , and acute radiation injury classification [set by Radiation Therapy Oncology Group (RTOG)] were observed in the two groups before and after treatment. The application time for antibiotics and glucocorticoids was compared between the two groups.

RESULTSAll patients completed this trial, and nobody dropped out or died. There was no statistical difference in Watters-CRP scores, KPS, or RTOG between the two groups before treatment (P > 0.05). Compared with before treatment in the same group, RTOG classification was obviously improved in the two groups (P < 0.05). Compared with the control group, Watters-CRP scores decreased, KPS increased, the application time for antibiotics and glucocorticoids was reduced (P < 0.05). The efficacy of RTOG classification was better in the treatment group than in the control group, but with no statistical difference between the two groups (P > 0.05).

CONCLUSIONZHG combined glucocorticoids and antibiotics was superior in treating radiation pneumonitis to using glucocorticoids or antibiotics alone in elevating Watters-CRP scores, shortening the application time for glucocorticoids and antibiotics, and improving patients' physical conditions.

Anti-Bacterial Agents ; therapeutic use ; Drug Therapy, Combination ; methods ; Drugs, Chinese Herbal ; therapeutic use ; Glucocorticoids ; therapeutic use ; Humans ; Karnofsky Performance Status ; Radiation Pneumonitis ; drug therapy

Viral nonstructural proteins in both enveloped and non-enveloped viruses play important roles in viral replication. Protein NS38 of Grass carp reovirus (GCRV), has been deduced to be a non-structural protein, and, consistent with other reoviruses, is considered to cooperate with the NS80 protein in viral particle assembly. To investigate the molecular basis of the role of NS38, a complete protein was expressed in E.coli for the first time. It was found that there is a better expression of NS38 induced with IPTG at 28 ℃ rather than 37 ℃. In addition, the antiserum of NS38 prepared with purified fusion protein and injected into rabbit could be used for detecting NS38 protein expression in GCRV infected cell lysate, while there is not any reaction crossed with purified virus particle, confirming NS38 is not a component of the viral structural protein. The result reported in this study will provide evidence for further viral protein-protein and protein-RNA interaction in dsRNA viruses replication.

OBJECTIVETo observe the clinical effect of Yufeng Capsule (YFC), a Chinese herbal preparation with function of clearing Heat-toxin in treating premonitory symptoms of apoplexy in middle and old aged patients.

METHODSOne hundred and fourteen patients with premonitory symptoms of apoplexy were treated with YFC and compared with 57 patients treated with Venoruton for control. The changes of clinical symptoms, anti-oxidation capability, blood lipid, blood sugar and hemorrheological parameters were observed.

RESULTS(1) The therapeutic effect in the YFC group was cured in 42 cases (36.84%), markedly effective in 38 (33.33%), effective in 28 (24.58%) and the total effective rate was 94.74%, while in the control group, the corresponding numbers were 9 (15.79%), 8(14.04%), 20(35.09%) and 64.91% respectively, the difference between the two groups in cure rate, markedly effective rate and total effective rate was significant (P < 0.05); (2) The whole blood viscosity, plasma viscosity, hemagglutination index and red blood cell deformity index in the YFC group were significantly improved after treatment (P < 0.01) and the improvement was better than those in the control group (P < 0.05 or P < 0.01); (3) Levels of serum malonyldialdehyde (MDA), superoxide dismutase (SOD), blood lipids and glucose were markedly improved in the YFC group (P < 0.05) after treatment, and showed a significant difference to those in the control group (P < 0.05).

CONCLUSIONYFC has obvious effect in treating premonitory symptoms of apoplexy patients, it could markedly improve the hemorrheologic parameters, regulate blood lipids and blood glucose metabolism, and strengthen the anti-oxidation capability of patients.

Aged ; Blood Viscosity ; drug effects ; Capsules ; Drugs, Chinese Herbal ; therapeutic use ; Erythrocyte Deformability ; drug effects ; Female ; Humans ; Ischemic Attack, Transient ; blood ; drug therapy ; Male ; Middle Aged ; Phytotherapy ; Superoxide Dismutase ; blood

To compare the characteristics of absorption and pharmacokinetic behavior of ginsenoside Rg1 (Rg1) with ginsenoside Rb1 (Rb1) of panax notoginseng saponins (PNS), bile excretion of both Rg1 and Rb1 were studied after i.v. and i.g. of PNS solution. Plasma protein binding ratios were studied using equilibrium dialysis method, and referred to pharmacokinetic parameters. It shows that (61.48 +/- 18.30)% dose of Rg1 and (3.94 +/- 1.49)% dose of Rb1 were separately excreted into bile 10 hours after i.v. administration (PNS 50 mg x mL(-1)), and (0.91 +/- 0.51)% dose of Rg1 and (0.055 +/- 0.02)% dose of Rb1 were excreted into bile 12 hours after i.g. administration (PNS 1 500 mg x mL(-1)). Plasma protein binding degrees of Rg1 and Rb1 were 6.56% - 12.74% and 80.1% - 89.69%, respectively. Stomach, intestinal and hepatic throughput efficiency (F(S), F1 and F(H)) for Rg1 were 49.85%, 13.05%, 50.56%, respectively, and 25.82%, 4.18%, 65.77% for Rb1. Therefore, poor intestinal absorption is a primary reason for the low bioavailability of both Rg1 and Rb1. Rg1 possesses relatively high bile excretion and low plasma protein binding rate, in contrast, Rb1 possesses low bile excretion and high plasma protein binding rate. Membrane permeability and elimination rate of Rb1 were lower than that of Rg1, meanwhile, longer MRT and bigger AUC could be found for Rb1.
Administration, Oral ; Animals ; Bile ; secretion ; Biological Availability ; Ginsenosides ; metabolism ; pharmacokinetics ; Intestinal Absorption ; Male ; Panax notoginseng ; chemistry ; Plants, Medicinal ; chemistry ; Protein Binding ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Saponins ; administration & dosage ; isolation & purification ; pharmacokinetics

Water in oil (W/O) microemulsion formulation was developed to enhance intestinal absorption of ginsenoside Rb1 (Rb1) of panax notoginseng (PNS). Effects of W/O microemulsions on pharmacokinetics after intraduodenal administration, membrane fluidity and membrane transport of Rb, were studied in rats, liposomes and parallel artificial membrane permeability assay (PAMPA), respectively. Soybean phospholipids/ethanol (SP/EtOH) was selected as surfactant/cosurfactant, together with PNS 400 mg x mL(-1) solution and various kinds of oils, to prepare 11 W/O microemulsions. Most of the microemulsions can enhance Rb1 intestinal absorption significantly. Besides surfactant/cosurfactant, oil also had an effect on the enhanced absorption and the order of enhancement was as follows: glyceryl laurate approximately = isopropyl myristate > isopropyl palmitate > 2-ethylhexanol palmitate. The effection of absorption enhancement by the long chain glyceride ( > C14) is lower than that by the medium chain glyceride (C8 - C14). Most of W/O microemulsions were found to enhance the membrane fluidity of liposomes to different extents. In PAMPA analysis, efficient permeability coefficient (Pe) of diluted-microemulsion (D-ME) is mostly higher than that of PNS solution, which indicated the components of microemulision can facilitate the membrane permeability of the drug. Meanwhile, linearity correlation between Pe and ratio of relative bioavailability (Fr) was acquired for undiluted microemulison (ME). Therefore, W/O microemulsions can enhance intestinal absorption of Rbr, and this effect may be attiributed to its enhancement on membrane fluidity to a certain degree. PAMPA analysis could be brought into not only the investigation of membrane transport of crude drug, but also conditioned preformulation research (e.g. absorption enhancer etc.).
Animals ; Drug Delivery Systems ; Emulsions ; Ginsenosides ; administration & dosage ; isolation & purification ; pharmacokinetics ; Intestinal Absorption ; Male ; Membrane Fluidity ; Oils ; Panax notoginseng ; chemistry ; Permeability ; Plants, Medicinal ; chemistry ; Polyethylene Glycols ; chemistry ; Rats ; Rats, Sprague-Dawley ; Surface-Active Agents ; chemistry ; Water

Objective: To observe the effect of electroacupuncture (EA) pretreatment on the protein expression of c-fos in fastigial nucleus (FN) and lateral hypothalamus area (LHA) in rats with acute myocardial ischemia-reperfusion injury (MIRI), and to explore the role and mechanism of FN and LHA in EA at the Heart Meridian fighting against acute MIRI reaction. Methods: Seventy Sprague-Dawley rats were randomly divided into a sham operation group, a model group, an EA-Heart Meridian group and an EA-Lung Meridian group, with 14 rats in each group; an LHA lesion plus EA-Heart Meridian group (LHA+EA-Heart Meridian group) and a FN lesion plus EA-Heart Meridian group (FN+EA-Heart Meridian group), with 7 rats in each group. Except the sham operation group, the left anterior descending branch of coronary artery was ligated to establish acute MIRI rat models in the other 5 groups. In the three groups with EA-Heart Meridian treatment, Shenmen (HT 7) and Tongli (HT 5) were selected; Taiyuan (LU 9) and Lieque (LU 7) were selected in the EA-Lung Meridian group. All the EA groups received EA stimulation prior to modeling, with 1 mA in current intensity and 2 Hz in frequency, 20 min each time, once a day for a total of 7 d. The sham operation group and the model group did not receive EA stimulation. The electrocardiogram was observed in the rats to analyze the ST-segment deviation and cardiac arrhythmia score. The expression of c-fos protein in FN and LHA was detected by immunohistochemistry method. Results: Compared with the sham operation group, the ST-segment deviation, cardiac arrhythmia score and the expression of c-fos protein in the FN and LHA increased significantly in the model group (all P<0.05). Compared with the model group, the ST-segment deviation, cardiac arrhythmia score and the expression of c-fos protein in FN and LHA decreased significantly in the EA-Heart Meridian group (all P<0.05). Compared with the EA-Heart Meridian group, the ST-segment deviation and cardiac arrhythmia score increased significantly in the EA-Lung Meridian group, LHA+EA-Heart Meridian group and FN+EA-Heart Meridian group (all P<0.05); the expression of c-fos in FN increased significantly in the EA-Lung Meridian group and LHA+EA-Heart Meridian group (both P<0.05); the expression of c-fos in LHA increased significantly in the EA-Lung Meridian group and FN+EA-Heart Meridian group (both P<0.05). Conclusion: FN and LHA are involved in the mechanism of EA at Heart Meridian to improve the acute MIRI reactions, and the cerebellum may participate in the improvement of cardiac function by EA through the cerebellum-hypothalamus projection.

AIMTo study the pharmacokinetics and relative bioavailability of probucol inclusion complex capsule.

METHODSFollowing oral administration of a single dose of 250 mg of conventional tablet (formulation A, purchased from the market) and probucol inclusion complex capsule (formulation B, a new formulation for preclinical trial) to each of 6 healthy dogs in a randomized crossover design, the plasma levels of the active drug at different time points were determined by HPLC and the plasma concentration-time profiles of formulation A and B were obtained. The pharmacokinetic parameters as well as relative bioavailability were analyzed.

RESULTSThe concentration-time curves of formulation A and formulation B were found to fit a two-compartment open model. The Tmax values of formulation A and formulation B were (9.3 +/- 2.1) h and (9.3 +/- 2.1) h, the Cmax values were (1.5 +/- 1.0) microgram.mL-1 and (2.3 +/- 0.9) microgram.mL-1 and the AUC0-240 values were (85 +/- 56) microgram.h.mL-1 and (134 +/- 55) microgram.h.mL-1, respectively. The relative bioavailability of formulation B was found to be (198 +/- 90)% compared with formulation A. The results of variance analysis and two one-side t-test showed that there was significant difference between the two formulations in the AUC0-240.

CONCLUSIONThe high bioavailability by the inclusion of formulation B is attributed to the improvement of its water-solubility by the inclusion process and this is supposed to be a key factor for improving drug bioavailability.

Administration, Oral ; Animals ; Anticholesteremic Agents ; administration & dosage ; pharmacokinetics ; Biological Availability ; Capsules ; Dogs ; Female ; Probucol ; administration & dosage ; pharmacokinetics ; Random Allocation ; Tablets

PURPOSE: The purpose of this study is to explore the dynamic change of brain-derived neurotrophic factor (BDNF) mRNA, protein, and tyrosine kinase-coupled receptor (TrkB) mRNA of the rat hippocampus under different stress conditions and to explore the influence of senescence on the productions expression. MATERIALS AND METHODS: By using forced-swimming in 4degrees C cold ice water and 25degrees C warm water, young and aged male rats were randomly divided into acute stress (AS) and chronic mild repeated stress (CMRS) subgroups, respectively. BDNF productions and TrkB mRNA in the hippocampus were detected by using Western-blotting and reverse transcription-polymerase chain reaction (RT-PCR), separately, at 15, 30, 60, 180, and 720 min after the last stress session. RESULTS: The short AS induced a significant increase in BDNF mRNA and protein in both age groups, but the changes in the young group were substantially greater than those of the aged group (p < 0.005). The CMRS resulted in a decrease in BDNF mRNA and protein, but a significant increase in TrkB mRNA in both young and age groups. The expression of BDNF mRNA and protein in the AS groups were higher than in the CMRS groups at 15, 30, and 60 min after stress. CONCLUSION: The results indicated that the up/down-regulation of BDNF and TrkB were affected by aging and the stimulus paradigm, which might reflect important mechanisms by which the hippocampus copes with stressful stimuli.
Animals ; Blotting, Western ; Brain-Derived Neurotrophic Factor/genetics/*metabolism ; Corticosterone/blood ; *Gene Expression Regulation ; Hippocampus/*metabolism ; Male ; Radioimmunoassay ; Random Allocation ; Rats ; Rats, Wistar ; Receptor, trkB/genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Stress, Physiological/genetics/*physiology

This study was aimed to investigate expression of vascular endothelial growth factor mRNA (VEGF mRNA) and its relationship with leukemic cell apoptosis after VEGF antisense oligonucleotide (VEGF ASODN) transferred into HL-60 cells. The phosphorothiate VEGF ODN was transferred into HL-60 cells in vitro by using cation poly mediated method, the inhibitory rate of cell proliferation was assayed by MTT, expression of VEGF mRNA was measured by RT-PCR, cell apoptosis was detected by cell morphology observation, DNA agarose gel electrophoresis and flow cytometer (FCM). The results showed that difference of the inhibitory rate of cell proliferation and the relative expression of VEGF mRNA between ASODN group and MSODN or control groups under the same condition (p < 0.05) was statistic significant, but no significant difference (p > 0.05) was found between MSODN and control. The number of clusters of cells in ASODN group decreased; the morphology features of apoptotic cells involved cell shrinking, more granulation in cytoplasm, nuclear contracting and many fragments of cells. In MSODN and control groups, however, cells were plump and clear, and grow healthly. The result of electrophoresis revealed DNA ladder in ASODN group, while only one band of DNA in control groups. The rate of cell apoptosis was 19.46% in ASODN group with a significant difference as compared with MSODN groups and control (p < 0.05). The rate of HL-60 cell apoptosis in combination of VEGF ASODN with VP16 was significantly higher than that in VP16 alone (p < 0.05) and showed time- and dose- dependence. It is concluded that VEGF ASODN can down-regulate expression of VEGF mRNA of HL-60 cells, induces the apoptosis, inhibits the proliferation of HL-60 cells and enhances VP16-induced apoptosis in HL-60 cells, the VEGF ASODN in combination with VP16 shows additive effect.
Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Etoposide ; pharmacology ; HL-60 Cells ; Humans ; Oligonucleotides, Antisense ; pharmacology ; RNA, Messenger ; metabolism ; Transfection ; Vascular Endothelial Growth Factor A ; metabolism