Preformulation study and initial determination of biological Properties of isopropylidene shikimic acid

Isopropylidene shikimic acid [ISA], a new drug derviatived from Shikimic Acid, had been proved to be effective in the cerebral protection after cerebral ischemia and reperfusion. But there was little research on the physical pharmacy and biopharmaceutical properties about the drug. In order to provide some useful data for the pharmaceutical development of ISA, the solubility, stability and Oil/Water partition coefficient [LogP] were determined by the classic preformulation study method, and the transmembrane performance of ISA was studied by Franz -diffusion cell method in vitro. The results showed that ISA was water-soluble with a solubility 32.52mg/ml, which could be improved to 44.32 mg/ml by 1% [w/v] sodium dodecyl sulfate; the LogP was -0.63; ISA was less stable in water but it was stable when pH greater than 6.0 and unstable when pH less than 6.0; the accumulated permeation rates at 1h were about 50% and more than 80% at 6h. Data obtained by the study indicated that the medium selection and pH control were important for liquid preparation of ISA, and avoiding dissolution and absorption in stomach was critical for the oral solid dosage forms. Mucosal drug delivery systems would be considered, according to the certain hydrophilic-lipophilic characters and good transmembrane capability

Study on anti-inflammatory activity of the main component of Girald Daphne Bark in vitro / 国际中医中药杂志

Objective To investigate the anti-inflammatory activity of the main active ingredients in the dried stem bark of Daphne giraldii Nitsche.Methods Severialchemical compounds like vladinol D, pinoresinol, daphneticin, daphnoretin, daphnetin, giraloid A and giraldoid B were isolated from the stem barks. The CCK-8 experiemnts were analyzed for the cytotoxicity study. The cells were divided into the control group, the model group and the treatment group according to random number table method. The control group and the model group were added with 50μl culture medium. Moreover, treatment group was added with different concentrations (50.00, 25.00, 12.50, 6.25, 3.12μg/ml) of the solutions of giraloid A, giraldoid B and daphneticin. Then, RAW264.7 cells were treated with 50μl LPS (4μg/ml) for 24 h in the model group and treatment group. Griess reagent was used to determine the amount of NO release, and the secretion of TNF-α was detected by ELISA kit.Results Cytotoxicity test indicated that giraldoid A (50.00μg/ml), giraldoid B (50.00μg/ml) and daphneticin (50.00μg/ml) showed noobvious cytotoxicity. Giraldoid B (12.50, 25.00, 50.00μg/ml) could inhibit the production of NO (271.86% ± 20.92%, 256.48% ± 20.92%, 199.31% ± 15.16%vs.358.62% ± 28.64%) and  TNF-α (647.87% ±115.79%, 618.42% ± 87.52%, 588.33% ± 87.94%vs. 1035.06% ± 58.29%) in RAW264.7 induced by LPS compared with the model group. Giraldoid A (25, 50μg/ml) could inhibit the production of NO (234.99% ± 34.28%, 167.36% ± 25.76% vs.358.62%±28.64%) and TNF-α (691.76% ± 60.37%, 534.01% ± 41.60% vs. 1035.06% ± 58.29%) in RAW264.7 induced by LPS compared with the model group. Daphneticin (12.5, 25, 50μg/ml) could inhibit the production of NO (283.89% ± 36.69%, 243.08% ± 48.19%, 225.92% ± 33.67% vs.358.62% ± 28.64%) and TNF-α (713.77% ± 121.96%, 670.62% ± 18.70% vs. 1035.06% ± 58.29%) in RAW264.7 induced by LPS compared with the model group.Conclusions Giraldoid A, giraldoid B and daphneticin exhi bited anti-inflammatory effect through inhibiting the release of NO and the production of TNF-α in RAW264.7 induced by LPS.

Effects of Different Processes ofBaijin Capsule on Treatment of Mice with Chronic / 中国中医药信息杂志

Objective To evaluate the efficacy of different processes ofBaijin Capsule to treatment of mice with chronic unpredictable stress-induced depression.Methods Chronic unpredictable stress was used to establish depression mice models. Experimental mice were divided into the following groups according to body mass: model group, positive medicine group, artware one (traditional process) high-dose and low-dose groups, and artware (refining process) two high-dose and low-dose groups. All medication groups were given relevant medicine for gavage. By detecting the two behavior indexes, immobility time of swimming and tail suspension of mice, the anti-depression effects of traditional process and refining process ofBaijin Capsule were investigated. By detecting autonomic activities and body mass, tested medicine was examined for function state of central excitation and changing animal body.Results The times for automatic activities ofBaijin Capsule in the model and artware (refining process) two high-dose and low-dose groups were (138.27±40.70)s, (100.01±34.75)s and (88.15±30.62)s, respectively, with statistical significance (P<0.01); the mice swimming immobility times in the model and artware (refining process) two low-dose groups were 668±19 and 705±24, respectively, with statistical significance (P<0.01); the mice tail suspension immobility times in model and artware (traditional process) one high-dose groups group were (28.14±1.25)g and (26.43±2.58)g, respectively, with statistical significance (P<0.05); the mice tail suspension immobility times in model and artware (refining process) two high-dose groups were (98.29±36.90)s and (87.54±30.05)s. Mice tail suspension immobility time in artware (refining process) two high-dose group decreased,without statistical significance.Conclusion Refining process ofBaijin Capsule can effectively be used to treat mice with chronic unpredictable stress-induced depression, and the efficacy is superior to the traditional process.

Alterations of Amino Acid Level in Depressed Rat Brain

Amino-acid neurotransmitter system dysfunction plays a major role in the pathophysiology of depression. Several studies have demonstrated the potential of amino acids as a source of neuro-specific biomarkers could be used in future diagnosis of depression. Only partial amino acids such as glycine and asparagine were determined from certain parts of rats' brain included hippocampi and cerebral cortex in previous studies. However, according to systematic biology, amino acids in different area of brain are interacted and interrelated. Hence, the determination of 34 amino acids through entire rats' brain was conducted in this study in order to demonstrate more possibilities for biomarkers of depression by discovering other potential amino acids in more areas of rats' brain. As a result, 4 amino acids (L-aspartic acid, L-glutamine, taurine and gamma-amino-n-butyric acid) among 34 were typically identified as potentially primary biomarkers of depression by data statistics. Meanwhile, an antidepressant called Fluoxetine was employed to verify other potential amino acids which were not identified by data statistics. Eventually, we found L-alpha-amino-adipic acid could also become a new potentially secondary biomarker of depression after drug validation. In conclusion, we suggested that L-aspartic acid, L-glutamine, taurine, gamma-amino-n-butyric acid and L-alpha-amino-adipic acid might become potential biomarkers for future diagnosis of depression and development of antidepressant.

Determination of plasma protein binding rate of isopropylidene-shikimic acid / 中国中药杂志

<p><b>OBJECTIVE</b>To study the plasma protein binding rate of isopropylidene-shikimic acid.</p><p><b>METHOD</b>The ultrafiltration was employed to determine the plasma protein binding rate of isopropylidene-shikimic acid. The plasma concentrations of isopropylidene-shikimic acid were measured by HPLC.</p><p><b>RESULT</b>The plasma protein binding rate of isopropylidene-shikimic acid with dog plasma at the concentration of 0.3, 0.15 g x L(-1) and 0.5 mg x L(-1) were (4.36 +/- 0.02)%, (4.12 +/- 0.19)% and (2.23 +/- 0.59)%, respectively. While the plasma protein binding rate of isopropylidene-shikimic acid with normal human plasma at the above concentrations were (11.23 +/- 0.01)%, (10.06 +/- 0.69)% and (9.72 +/- 0.59)%, respectively.</p><p><b>CONCLUSION</b>The binding rate of isopropylidene-shikimic acid with plasma protein is low.</p>