Insights into the suanzaoren mechanism—From constructing the 3D structure of GABA-A receptor to its binding interaction analysis

Xie

International Journal of Food Properties

et al. 2014

Jujuboside A (JuA) is a representative saponin with significant sedative and hypnotic effects.Up to now, there were many arguments on its metabolic mechanism. In this study, a high performance liquid chromatography-tandem mass spectrometry (MS/MS) method was developed for investigating the degradation characteristics of JuA incubated with rat feces. With the method, the degradation kinetics of JuA was studied. The results showed JuA decomposed rapidly. It could decompose nearly 100% in only 4-6 h. The degradation regularity was consistent with the first dynamic process. In addition, seven metabolites were determined and identified to be the serial hydrolysis products of JuA. The results revealed that gastrointestinal microbiota played an indispensable role in the metabolic process of JuA. JuA may be a supplier of sugars under the hydrolysis effect induced by the bacterial enzymes. At the same time, its aglycone was produced as a by-product, which could be easier to be absorbed into the body to perform its specific bioactivities.

Section: Introductionsupporting

confidence: 87%

Degradation Kinetics of Jujuboside a by Rat Intestinal Flora and Identification of the Metabolites by HPLC-Ms/Ms

Xie

International Journal of Food Properties

et al. 2014

“…This is the first reported evidence that JuA could be transferred into the brain, which implied that the original type of JuA, not only its degradation product, exerts the specific bioactivity. [13][14][15] In this study, for the first time, it was found that JuA could pass into the brain through the blood-brain barrier. …”

Section: Distribution In Different Tissuesmentioning

confidence: 65%

“…[9][10][11][12] In recent years, Chen pointed out that JuA was not the real effective ingredient with sedative function in ZSS. [13,14] Due to its comparatively large structure, it was difficult for JuA to be absorbed into the body, especially pass through the blood-brain barrier with the original type. [15] Liu et al had already observed that JuA could be absorbed into rat plasma after oral administration; [16] nevertheless, there have been no reports on the tissue distribution of JuA up to now.…”

Section: Introductionmentioning

confidence: 99%

Tissue Distribution of Jujuboside A in Sprague-Dawley Rats Determined by an Efficient HPLC–ESI-MS/MS Method

Journal of Liquid Chromatography & Related Technologies

Xie

2014

Jujuboside A (JuA), a dammarane-type triterpene glycoside, is a main bioactive saponin in Zizyphi Spinosi Semen (a traditional Chinese herbal food). In this research, the distribution of JuA in Sprague-Dawley rats was investigated with a new and efficient HPLC-ESI-MS=MS method. The results showed that JuA distributed rapidly and widely in various rat tissues (including heart, liver, spleen, kidney, and lung) after intravenous administration. In addition, it was initially found that JuA could pass through the blood-brain barrier and reach various areas of the brain quickly. At 0.25 hr, the concentration of JuA in the hippocampus (204.10 ng Á g À1 ) was significantly higher than in the cerebrum (144.27 ng Á g À1 ), olfactory bulb (98.42 ng Á g À1 ), and corpus striatum (76.04 ng Á g À1 ) (p < 0.05), indicating that the hippocampus was the main accumulation area of JuA in the brain.

“…In the past few years, we had focused on computer-aided drug design (CADD) in several researches [14][15][16][17][18][19][20][21] . In our experience, before the de novo design, a suitable scoring function should be selected to evaluate the protein-ligand interaction.…”

Section: Introductionmentioning

confidence: 99%

Discovery of potent inhibitors for phosphodiesterase 5 by virtual screening and pharmacophore analysis

et al. 2009

Self Cite

Aim: To explore the potent inhibitor from one of the Traditional Chinese medicine (TCM), Epimedium sagittatum. Methods: We predicted the potent compound, eS03b, de novo evolution from the four Epimedium sagittatum components were verified by molecular docking, pharmacophore analysis, and analysis of quantitative structure-activity relationship (QSAR) model, which was constructed by multiple linear regression. Results: ES03b was chosen to undergo drug modification via de novo evolution. By analyzing the pharmacophore features, we found that the hydrophobic core in the binding site and the hydrogen bond generated at Asn663 played key roles in designing PDE5 inhibitors. eS03b generated 49 diversities (evo01-49). evo48 had high activity in prediction. Although the value of prediction was overestimated, evo48 was suggested as the potent lead. Conclusion: In this study, we showed that the hydrophobic core in the binding site and hydrogen bond production on Asn663 played key roles to design PDE5 inhibitors. From several require validation analysis, Evo48 was suggested to be a potent inhibitor.