Garcinia Glycosides is a candidate drug obtained by structural modification of Gambogic Acid (GA), which was acquired through High Throughput Screening(HTS). As Garcinia Glycosides is an effective but insoluble anti-t...Garcinia Glycosides is a candidate drug obtained by structural modification of Gambogic Acid (GA), which was acquired through High Throughput Screening(HTS). As Garcinia Glycosides is an effective but insoluble anti-tumor drug, the aim of this study was to obtain a solid dispersion form Garcinia Glycosides by using solvent-melt method so that improve the solubility and dissolution rate. The solid dispersion was characterized by High Performance Liquid Chromatography (HPLC), infrared spectroscopy and evaluated the intestinal absorption of the drug by rat in situ single pass intestinal perfusion. The results showed the increase of solubility, dissolution velocity and absorption compared to other forms. This indicated that solid dispersion could greatly improve the relative bioavailability of Garcinia Glycosides in vivo.展开更多
AIM: To investigate the absorption characteristics of the total alkaloids from Mahoniae Caulis(TAMC) through the administration of monterpene absorption enhancers or protein inhibitors. METHOD: The absorption behavior...AIM: To investigate the absorption characteristics of the total alkaloids from Mahoniae Caulis(TAMC) through the administration of monterpene absorption enhancers or protein inhibitors. METHOD: The absorption behavior was investigated in an in situ single-pass intestinal perfusion(SPIP) assay in rats. RESULTS: The intestinal absorption of TAMC was much more than that of a single compound or a mixture of compounds(jatrorrhizine, palmatine, and berberine). Promotion of absorption by the bicyclic monoterpenoids(borneol or camphor) was higher than by the monocyclic monoterpenes(menthol or menthone), and promotion by compounds with a hydroxyl group(borneol or menthol) was higher than those with a carbonyl group(camphor or menthone). The apparent permeability coefficient(Papp) of TAMC was increased to 1.8-fold by verapamil, while it was reduced to one half by thiamine. The absorption rate constant(Ka) and Papp of TAMC were unchanged by probenecid and pantoprazole. CONCLUSION: The intestinal absorption characteristics of TAMC might be passive transport, and the intestinum tenue was the best absorptive site. In addition, TAMC might be likely a substrate of P-glycoprotein(P-gp) and organic cation transporters(OCT), rather than multidrug resistance protein(MRP) and breast cancer resistance protein(BCRP). Compared with a single compound and a mixture of compounds, TAMC was able to be absorbed in the blood circulation effectively.展开更多
Objective: The intestinal absorption characteristics of active ingredients are very important for oral administration of traditional Chinese medicine(TCM) to achieve the desired therapeutic effect.However, a deeper un...Objective: The intestinal absorption characteristics of active ingredients are very important for oral administration of traditional Chinese medicine(TCM) to achieve the desired therapeutic effect.However, a deeper understanding about active ingredients absorption characteristics is still lack. The aim of this study was to investigate the absorption properties and mechanism of rhubarb active ingredients in TCM preparation and pure form.Methods: The intestinal absorption behavior of active ingredients in Shenkang extract(SKE) and rhubarb anthraquinone ingredients(RAI) were investigated by in situ single-pass intestinal perfusion model. And the bidirectional transport characteristics of these active ingredients were assessed by in vitro Caco-2 cell monolayer model.Results: In situ experiment on Sprague-Dawley rats, the effective permeability coefficient values of aloeemodin, emodin and chrysophanol in RAI were higher than those in SKE, and the value of rhein in RAI was lower than that in SKE. But the easily absorbed segments of intestine were consistent for all ingredients,whether in SKE or in RAI. In vitro experiment, the apparent permeability coefficient values of rhein, emodin and chrysophanol in RAI were higher than those in SKE, and this value of aloe-emodin in RAI was lower than that in SKE. But their efflux ratio(ER) values in SKE and RAI were all similar.Conclusion: Four rhubarb anthraquinone ingredients in SKE and RAI have similar absorption mechanism and different absorption behavior, and the microenvironment of the study models influenced their absorption behavior. The results may provide an aid for understanding of the absorption characteristics of the TCM active ingredients in complex environments and the complementarities of different research models.展开更多
文摘Garcinia Glycosides is a candidate drug obtained by structural modification of Gambogic Acid (GA), which was acquired through High Throughput Screening(HTS). As Garcinia Glycosides is an effective but insoluble anti-tumor drug, the aim of this study was to obtain a solid dispersion form Garcinia Glycosides by using solvent-melt method so that improve the solubility and dissolution rate. The solid dispersion was characterized by High Performance Liquid Chromatography (HPLC), infrared spectroscopy and evaluated the intestinal absorption of the drug by rat in situ single pass intestinal perfusion. The results showed the increase of solubility, dissolution velocity and absorption compared to other forms. This indicated that solid dispersion could greatly improve the relative bioavailability of Garcinia Glycosides in vivo.
基金supported by China Pharmaceutical University Training Programs of Innovation for Undergraduates(No.02640390)
文摘AIM: To investigate the absorption characteristics of the total alkaloids from Mahoniae Caulis(TAMC) through the administration of monterpene absorption enhancers or protein inhibitors. METHOD: The absorption behavior was investigated in an in situ single-pass intestinal perfusion(SPIP) assay in rats. RESULTS: The intestinal absorption of TAMC was much more than that of a single compound or a mixture of compounds(jatrorrhizine, palmatine, and berberine). Promotion of absorption by the bicyclic monoterpenoids(borneol or camphor) was higher than by the monocyclic monoterpenes(menthol or menthone), and promotion by compounds with a hydroxyl group(borneol or menthol) was higher than those with a carbonyl group(camphor or menthone). The apparent permeability coefficient(Papp) of TAMC was increased to 1.8-fold by verapamil, while it was reduced to one half by thiamine. The absorption rate constant(Ka) and Papp of TAMC were unchanged by probenecid and pantoprazole. CONCLUSION: The intestinal absorption characteristics of TAMC might be passive transport, and the intestinum tenue was the best absorptive site. In addition, TAMC might be likely a substrate of P-glycoprotein(P-gp) and organic cation transporters(OCT), rather than multidrug resistance protein(MRP) and breast cancer resistance protein(BCRP). Compared with a single compound and a mixture of compounds, TAMC was able to be absorbed in the blood circulation effectively.
基金supported by the National Natural Science Foundation of China (No. 81673397)the Natural Science Basic Research Plan in Shaanxi Province of China (No. 2020JM-023)。
文摘Objective: The intestinal absorption characteristics of active ingredients are very important for oral administration of traditional Chinese medicine(TCM) to achieve the desired therapeutic effect.However, a deeper understanding about active ingredients absorption characteristics is still lack. The aim of this study was to investigate the absorption properties and mechanism of rhubarb active ingredients in TCM preparation and pure form.Methods: The intestinal absorption behavior of active ingredients in Shenkang extract(SKE) and rhubarb anthraquinone ingredients(RAI) were investigated by in situ single-pass intestinal perfusion model. And the bidirectional transport characteristics of these active ingredients were assessed by in vitro Caco-2 cell monolayer model.Results: In situ experiment on Sprague-Dawley rats, the effective permeability coefficient values of aloeemodin, emodin and chrysophanol in RAI were higher than those in SKE, and the value of rhein in RAI was lower than that in SKE. But the easily absorbed segments of intestine were consistent for all ingredients,whether in SKE or in RAI. In vitro experiment, the apparent permeability coefficient values of rhein, emodin and chrysophanol in RAI were higher than those in SKE, and this value of aloe-emodin in RAI was lower than that in SKE. But their efflux ratio(ER) values in SKE and RAI were all similar.Conclusion: Four rhubarb anthraquinone ingredients in SKE and RAI have similar absorption mechanism and different absorption behavior, and the microenvironment of the study models influenced their absorption behavior. The results may provide an aid for understanding of the absorption characteristics of the TCM active ingredients in complex environments and the complementarities of different research models.
