Study on compatibility of active ingredients of Simiao Yongan Decoction in rats with in situ single-pass intestinal perfusion model / 中国中药杂志

To study the compatibility rule of Simao Yongan Decoction,the rat single pass intestinal perfusion model in situ was used in this study. On the basis of early research,the five kinds of anti-inflammatory active ingredients,i.e. chlorogenic acid,liquiritin,hyperoside,angoroside C and isochlorogenic acid C in Simao Yongan Decoction were selected as research objects. The contents of the above five actives compounds with various compatibility combinations and in different intestinal segment perfusates were determined by using the method of ultra-performance liquid chromatography-mass spectrometry( UPLC-MSn). The kinetic parameters of intestinal absorption of the five anti-inflammatory active ingredients were calculated,which could be used to evaluate the intestinal absorption of each component in different combinations. The results showed that the absorption parameters of liquiritin in ileum were highest in Glycyrrhizae Radix et Rhizoma single herb,while the absorption parameters of other four components in ileum and duodenum were highest in the compatible combinations. Among them,the absorption parameters of chlorogenic acid in ileum and duodenum were highest in the whole prescription compatibility; ischlorogenic acid C showed higher absorption levels in the whole prescription and the herb compatibility of Lonicerae Japonicae Flos-Scrophulariae Radix-Glycyrrhizae Radix et Rhizoma. However,the absorption levels of hyperoside and angoroside C in different compatibilities were quite different in ileum and duodenum. In this study,the intestinal absorption of five anti-inflammatory active ingredients in Simiao Yongan Decoction with different compatibility combinations was investigated,revealing that the absorption of active ingredients varied with the different compatibility combinations and different intestinal segments. At the same time,the above research also indicated that the absorption of active ingredients could be obviously promoted by the compatibility of compound prescriptions,laying a foundation for the research on the compatibility rule of Simiao Yongan Detection from the biological point of view.

Intestinal absorption of phenolic acids in Rhus chinensis extracts by in situ single-pass perfusion model in rats / 中国中药杂志

The intestinal absorption properties of four main effective components(gallic acid, ocinolglucoside, ethyl gallate and penta-O-galloyl-β-D-glucose) in Rhus chinensis extracts were investigated by in situ single-pass intestinal perfusion model in rats. The liquid accumulation of perfusion was corrected by gravimetry. The HPLC method was established to determine the concentration of the four effective components in the intestinal perfusion. It showed significant differences(Pethyl gallate>gallic acid>ocinolglucoside, with significant differences between them(P<0.05). In conclusion, gallic acid, orpheolglucoside, ethyl gallate and pentacyl-glucose could be absorbed in the whole intestine. Their absorption rate and permeation ability were related to the intestinal section and the perfusate concentration. These results indicated potential active transport or facilitated diffusion in the intestinal transport process of the four effective components.

Study on the Absorption Characteristics of Naringin in situ Single-pass Intestinal Perfusion Model of Rats / 中国药房

OBJECTIVE:To study absorption characteristics of naringin in situ single-pass intestinal perfusion model of rats. METHODS:UPLC method was established for the content determination of naringin and naringenin in intestinal perfusion samples of rats. The in situ single-pass intestinal perfusion model of rats was adopted to investigate intestinal(duodenum,jejunum,ileum and colon)absorption and metabolic characteristics [apparent permeability coefficient(Peff),absorptivity,metabolic rate] of naringin(10 μ mol/L). RESULTS:The linear range of naringin and naringenin were 1.25-40,1.25-40 μ mol/L(R2=0.999 4, 0.996 6). The detection limit were 0.5,0.4 μ mol/L,and limit of quantitation were all 1.25 μ mol/L. Precision of inter-day and intra-day,recovery and stability in HBSS solution,perfusion fluid of small intestine and colon were all in line with the standard. Peffof naringin in duodenum,jejunum,ileum and colon of rats were(0.28 ± 0.19),(0.71 ± 0.17),(0.30 ± 0.02),(0.59 ± 0.19) (n=6),without statistical significance(P>0.05).Absorptivities were(2.90±2.14)%,(6.38±3.61)%,(3.69±0.56)%,(6.64± 2.12)%(n=6). Naringin could be metabolized to naringenin in 4 intestinal segments of rats,with metabolic rate of(2.98 ± 1.51)%,(2.53 ± 1.31)%,(2.24 ± 1.33)%,(0.70 ± 0.20)%(n=6). The lowest absorptivity and the highest metabolic rate of naringin were occurred in the duodenum,there were statistical significance compared with colon(P<0.05). CONCLUSIONS:Naringin shows poor permeability and poor absorption in the intestinal tract of rats.There was no specific absorption site in the rat' s intestines for naringenin;naringin could be metabolized to naringenin in small intestine and colon,but metabolic rate of naringin in small intestine is higher than in colon.

Research on intestinal permeability of glycyrrhetinic acid in multicomponent environment / 中草药

Objective: To investigate the characteristics of intestinal absorption of glycyrrhetinic acid in rats in the multicomponent environment. Methods: The effect of multicomponent environment on intestinal absorption of glycyrrhetinic acid was investigated in rat model of in situ single-pass intestinal perfusion, HPLC was used to determine the concentration of glycyrrhetinic acid in intestinal perfusion fluid samples, the effective permeability coefficient (Peff), absorption rate constant (Ka), and absorption fraction (Fa) of glycyrrhetinic acid in rats ileum were calculated, the effects of glycyrrhetinic acid with different mass concentration and P-glycoprotein (P-gp) inhibitor verapamil, as well as the compatibility of different components on intestinal absorption of glycyrrhetinic acid were examined,. Results: The Peff, Ka, and Fa values of glycyrrhetinic acid perfusion liquid (10 and 20 µg/mL) in the ileum segment had no significant difference. Added with 100 µmol/L verapamil, Peff, and Fa values of 10 µg/mL glycyrrhetinic acid increased, which illustrated that the glycyrrhetinic acid might be the substrate of P-gp; In two components compatibility, the effect of baicalin on absorption of glycyrrhetinic acid was the most obvious, Peff value of glycyrrhetinic acid was from (4.05 ± 0.78) × 10-5 cm/s to (2.18 ± 0.63) × 10-5 cm/s, and the penetration of glycyrrhetinic acid was reduced. The puerarin consociation baicalin and berberine had no obvious effect on permeability of glycyrrhetinic acid. In the three components compatibility condition, the experimental results showed that after glycyrrhetinic acid combined with puerarin and berberine, the permeability coefficient did not change, while the permeability coefficient changed, but not obviously, glycyrrhetinic acid combined with baicalin and berberine had lower permeability, Peff values were from (4.05 ± 0.78) × 10-5 cm/s down to (1.35 ± 0.69) × 10-5 cm/s, and the effects of baicalin on glycyrrhetinic acid was evident. Conclusion: Glycyrrhetinic acid can be absorbed in the ileum of rats, and has no obvious influence on Peff and Ka values within a certain range of quality concentration. The absorption mechanism is determined to be passive diffusion, glycyrrhetinic acid is substrate of P-gp, and saturation phenomenon exists transporters; Baicalin has significant effects on glycyrrhetinic acid absorption, which may be related to the induction by P-pg expression, increasing the glycyrrhetinic acid from cell to the extracellular discharge, reducing the penetration of glycyrrhetinic acid, and influencing the absorption.

Intestinal Absorption Characters of Mosapride Citrate Using Caco-2 Cells and Single-Pass Intestinal Perfusion Methods / 中国药学杂志

OBJECTIVE: To investigate the intestinal absorption characters of mosapride citrate(MC) and its tablets. METHODS: The Caco-2 cell monolayer was cultured and the in situ single-pass intestinal perfusion(SPIP) in rat model was created for studying the drug absorption properties, using phenol red method to revise the perfusate volume, a HPLC method was developed to simultaneously detect the phenol red and MC, the absorptive coefficient of Papp and Peff was calculated. RESULTS: MC was absorbed by the whole intestine segments in rats, mainly at upper small intestine. The tablets showed high permeability and good intestinal absorption in Caco-2 cells and SPIP in rats. CONCLUSION: In the Caco-2 cells and rats SPIP models, the tablets are prepared showed good consistency with the branded drug.

Laminaria japonica increases plasma exposure of glycyrrhetinic acid following oral administration of Liquorice extract in rats / 中国天然药物

The present study was designed to investigate the effects of Laminaria japonica (Laminaria) on pharmacokinetics of glycyrrhetinic acid (GA) following oral administration of Liquorice extract in rats. Following oral administrations of single-dose and multi-dose Liquorice extract and Liquorice-Laminaria extract, respectively, plasma samples were obtained at various times and the concentrations of GA, liquiritigenin, and isoliquiritigenin were measured by LC-MS. The effects of Laminaria extract on pharmacokinetics of GA were also investigated, following single-dose and multidose of glycyrrhizic acid (GL). The effects of Laminaria extract on intestinal absorption of GA and GL were studied using the in situ single-pass intestinal perfusion model. The metabolism of GL to GA in the contents of small and large intestines was also studied. The results showed Liquorice-Laminaria extract markedly increased the plasma concentration of GA, accompanied by a shorter Tmax. Similar alteration was observed following multidose administration. However, pharmacokinetics of neither liquiritigenin nor isoliquiritigenin was affected by Laminaria. Similarly, Laminaria markedly increased concentration and decreased Tmax of GA following oral GL were observed. The data from the intestinal perfusion model showed that Laminaria markedly increased GL absorption in duodenum and jejunum, but did not affect the intestinal absorption of GA. It was found that Laminaria enhanced the metabolism of GL to GA in large intestine. In conclusion, Laminaria increased plasma exposures of GA following oral administration of liquorice or GL, which partly resulted from increased intestinal absorption of GL and metabolism of GL to GA in large intestine.

Absorption characteristics of the total alkaloids from Mahonia bealei in an in situ single-pass intestinal perfusion assay / 中国天然药物

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.