Effect of processing excipient suet oil on formation and absorption of baohuoside Ⅰ-bile salt self-assembled micelles / 中国中药杂志

The fried method with suet oil,which can strengthen the effect of Epimedium in warming kidney and enhancing Yang,has been widely used in the processing of Epimedium in traditional Chinese medicine. Based on the formation mechanism of Epimedium flavonoids self-assembled micelles in vivo,the synergistic mechanism of processing excipient suet oil was investigated in this paper from the perspective of pharmaceutics. Baohuoside Ⅰ,as representative component of processed Epimedium,was selected as model drug.Average size and zeta potential were measured and the morphology of micelles was observed under transmission electron microscopy. Caco-2 monolayer cell model,rat intestinal perfusion model and in vivo serum drug concentration method were established to investigate the effect of suet oil on the formation and absorption of the baohuosideⅠ bile salt self-assembled micelles. Baohuoside Ⅰ can form selfassembled micelles under the action of sodium deoxycholate. While,adding suet oil into the baohuoside Ⅰ-bile salt micelles( BSDOC) can make it form a more stable system with a smaller average size,higher Zeta potential,lower polydispersity index( PDI) value,significantly improved encapsulation efficiency and drug loading,indicating that suet oil could significantly improve the micelle formation in vivo. In addition,the permeability coefficient of baohuoside Ⅰ in Caco-2 monolayer cells and the four intestinal organs( duodenum,jejunum,ileum and colon) was increased and the oral bioavailability was also improved after adding the suet oil to BS-DOC.All the results demonstrated that the suet oil can promote the formation and absorption of baohuoside Ⅰ self-assembled micelles,so as to enhance its synergistic effects.

Carbon monoxide-releasing molecule-2 attenuates LPS induced barrier injure of Caco-2 cells / 中华急诊医学杂志

Objective To investigate the effects and mechanisms of carbon monoxide-releasing molecule-2 (CORM-2) on LPS induced barrier injure of Caco-2 cells.Methods The model of Caco-2 monolayer cells damage induced by LPS was established by using 50 μg/ml LPS for 24 hours.After preconditioning with different concentrations (10 μmol/L,50 μmol/L,and 100 μ mol/L) of CORM-2 for 1 hour,the cultured well-grown Caco-2 monolayer cells were stimulated with 50 μ g/ml lipopolysaccharides (LPS) for 24 hour.The 100 μmol/L CORM-2 was put into 37℃ and 5％ CO2 incubator for 18 hours until the CO has been fully released,and it became an inactive CORM-2(iCORM-2).The cultured Caco-2 monolayer cells were divided into six groups:the control group,the LPS group,the LC1(10 μmol /L CORM-2 preconditioning) group,the LC2(50 μmol/L CORM-2 preconditioning) group,the LC3(100 μmol/L CORM-2 preconditioning) group,and the LC4 (iCORM-2 preconditioning) group.The apoptosis rates of different groups of Caco-2 monolayer cells were detected using flow cytometry.Cytokines (TNF-α,IL-1β and HMGB-1) levels of different groups were detected using ELISA kits.The levels of tight junction proteins (occludin ZO-1,claudin-1 and claudin-4) of every group were detected using Western blotting with specific antibodies.The structural changes of tight junction proteins were visualized by immunofluorescence technique.Results Compared with control group,cell apoptosis rate and release of inflammatory cytokines such as TNF-α,IL-1β and HMGB-1 in LPS group were significantly higher,and the levels of tight junction proteins were apparently decreased (P＜0.05) in LPS group.Compared with LPS group,cell apoptosis rate and release of inflammatory cytokines such as TNF-α,IL-1β and HMGB-1 decreased,and the levels of tight junction proteins were attenuated obviously,P＜0.05,in CORM-2 preconditioning groups.And the higher the concentration of CORM-2,the more obvious the protective effects.Conclusions This study demonstrates that CORM-2,as one of exogenous CO-releasing molecules,has the capacity to protect the barrier damage of LPS-stimulated Caco-2 monolayer cells in a concentration dependent manner.The higher the concentration of CORM-2 was,the stronger the protective effects were.The protective effects of CORM-2 include reducing Caco-2 monolayer cells apoptosis rate,inhibiting inflammatory cytokines production and release,and restoring distribution and levels of tight junction proteins.

Effects of 10 furanocoumarins in Angelica dahurica on intestinal transport of vincristine / 中草药

Objective: To study the effects of 10 kinds of furanocoumarines in Angelica dahurica (oxypeucedanin, isoimperatorin, phellopyerin, isoimperatorin, imperatorin, byakangelicol, angelicin, scopoletin, umbelliferone, and byakangelicine) on the intestinal absorption and transportation of vincristine. Methods: The apparent permeability coefficient (Papp) of vincristin was used as evaluated parameter, and Caco-2 (human colon cancer cell lines) cell monolayer was used as intestinal epithelial cell model to study the effects of 10 furanocoumarins on transportation of vincristine in Caco-2 cell monolayer. Results: There were different effects of the 10 furanocoumarins on transportation of vincristine. Oxypeucedanin, isoimperatorin, and imperatorin could improve the transport of vincristine in Caco-2 cell monolayer (P < 0.05), while isoimperatorin, byakangelicol, angelicin, umbelliferone, and byakangelicine could inhibit the transport of vincristine in Caco-2 cell monolayer (P < 0.01). However, phellopyerin and scopoletin have no effects on the transport of vincristine on Caco-2 cell. Conclusion: Different kinds of furanocoumarins have different effects on intestinal transport of vincristine, which may be related to the structure of furocoumarins and the functional group about their connection.