As a novel oral drug delivery system, proliposome was applied to improve the solubility of active components of Ginkgo biloba extract (GbE). There are currently few reports focusing on the pharmacokinetic characteristics of proliposome of GbE (GbP). A rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of active components of GbP and a commercial tablet product (Ginaton) in rat plasma was developed and successfully validated. The method was applied to the comparative pharmacokinetic evaluation of GbP and Ginaton in rat plasma. The results indicated that GbP has a significant effect on absorption, elimination and bioavailability of flavonoids and terpenoid lactones in comparison with Ginaton. The obtained results would be helpful for evaluating the absorption mechanism in the gastrointestinal tract in pharmacokinetic level and guiding the development of the novel oral drug delivery system.
Marasmius androsaceus, a well‑known medical fungus, possesses antihypertensive, analgesic and antioxidant effects. Exopolysaccharide (EPS), produced by microorganism secretion, exerts various types of biological activities. The present study aimed to investigate the antidepressant‑like effect of the EPS produced during Marasmius androsaceus submerge fermentation (MEPS). Based on the assessment of acute toxicity and behavior, a forced swimming test (FST), tail suspension test (TST), 5‑hydroxytryptophan‑induced head‑twitch assessment and reserpine‑induced hypothermia assessment were performed. The administration of MEPS for 7 days enhanced mouse locomotor and balance ability in the mice. Similar to the results following treatment with fluoxetine, which was used as positive control drug, MEPS significantly decreased the duration of immobility in the FST and TST, increased head twitches in the 5‑HTP‑induced head‑twitch test and enhanced rectal temperature in resperpine‑induced hypothermia. MEPS altered the abnormal concentrations of 5‑hydroxytryptamine, 5‑hydroxyindoleacetic acid, dopamine and norepinephrine in the hypothalamus in the resperine‑induced mouse model. Additionally, an increase in the expression of tyrosine hydroxylase and a reduction in the level of dopamine transporter in the hypothalamus were noted following 7 days of MEPS administration. Taken together, the EPS produced during MEPS exhibited antidepressant‑like effects, which may be associated with its regulation on the dopaminergic system. The results of the present study provide experimental evidence supporting the clinical use of MEPS as an effective agent against depression.
Using desirability function, four indexes including mycelium dry weight, intracellular polysaccharide, adenosine and mannitol yield were uniformed into one expected value (Da) which further served as the assessment criteria. In our present study, Plackett-Burman design was applied to evaluate the effects of eight variables including initial pH, rotating speed, culture temperature, inoculum size, ventilation volume, culture time, inoculum age and loading volume on Da value during Marasmius androsaceus submerged fermentation via a five-liter fermentor. Culture time, initial pH and rotating speed were found to influence Da value significantly and were further optimized by Box-Behnken design. Results obtained from Box-Behnken design were analyzed by both response surface regression (Design-Expert.V8.0.6.1 software) and artificial neural network combining the genetic algorithm method (Matlab2012a software). After comparison, the optimum M. androsaceus submerged fermentation conditions via a five-liter fermentor were obtained as follows: initial pH of 6.14, rotating speed of 289.3 rpm, culture time of 6.285 days, culture temperature of 26 °C, inoculum size of 5%, ventilation volume of 200 L/h, inoculum age of 4 days, and loading volume of 3.5 L/5 L. The predicted Da value of the optimum model was 0.4884 and the average experimental Da value was 0.4760. The model possesses well fitness and predictive ability.
Paclitaxel is known as one of the most effective anticancer drugs. Near Infrared Spectroscopy (NIRS), a rapid, precise and non-destructive approach of analysis, has been widely used for qualitative and quantitative detection. The present study aims to analyze the plasma paclitaxel concentration with NIRS. Various batches of plasma samples were prepared and the concentration of paclitaxel was determined via high performance liquid chromatography tandem mass spectrometry (LC-MS/MS). The outliers and the number of calibration set were confirmed by Monte Carlo algorithm combined with partial least squares (MCPLS). Since NIR spectra may be contaminated by signals from background and noise, a series of preprocessing were performed to improve signal resolution. Moving window PLS and radical basis function neural network (RBFNN) methods were applied to establish calibration model. Although both PLS and RBFNN models are well-fitting, RBFNN-established model displayed better qualities on stability and predictive ability. The correlation coefficients of calibration curve and prediction set (Rc(2) and Rp(2)) are 0.9482 and 0.9544, respectively. Moreover, independent verification test with 20 samples confirmed the well predictive ability of RBFNN model.
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