Study on the intestinal absorption characteristics of saikosaponins / 中国药房

OBJECTIVE To explore the intestinal absorption characteristics of saikosaponins. METHODS Based on everted intestinal sac model， using accumulative absorption amount （Q） and absorption rate constant （Ka） as indexes， UHPLC-MS/MS technique as a method， the absorption of saikosaponin A， B2， C， D and F from total saponins of Bupleurum chinense （8 g/mL， by crude drug） in the duodenum， jejunum and ileum was detected. RESULTS The correlation coefficients （r） of the regression equations for the absorption of saikosaponins A， B2， C and F in the duodenum， jejunum and ileum were all higher than 0.95， while the r of saikosaponin D in the above intestinal segments was lower than 0.95； compared with the absorption of the same composition in the duodenum， the Q and Ka of saikosaponin A and C circulating in jejunum and ileum for 120 min， as well as the Q and Ka of saikosaponin F circulating in the ileum for 120 min were significantly decreased （P＜0.05）. CONCLUSIONS Saikosaponin A and the other 4 saikosaponins are all absorbed in the duodenum， jejunum and ileum； among them， saikosaponin A， B2， C and F are linearly absorbed， which conforms to the zero-order absorption characteristics， but saikosaponin D shows non- linear absorption.

Study on the mechanism of "guiding action" of borneol in Suxiaojiuxin pills / 药学学报

In order to research the mechanism of guiding action of borneol in Suxiaojiuxin pills, the model of in vitro intestinal absorption, in vivo drug metabolism of mice and cell in vitro absorption model of Caco-2 were established firstly. All animal experiments were in accordance with the regulations of the Animal Ethics Committee of Nankai University. The results showed that the cumulative absorption quantity and absorption permeability of ferulic acid and ligustilide in the intestinal juice of Suxiaojiuxin pills group were significantly increased comparing with fake Suxiaojiuxin pills group, which don't contain borneol. By using borneol, the content of ferulic acid and ligustilide in the blood and tissues, such as heart, were added. The transepithelial resistance value and the content of horseradish peroxidase (HRP) in Caco-2 were rapidly decreased and increased, respectively. Due to further explore mechanism of promoting intestinal absorption of borneol for drugs, in this study, photosensitive probes of borneol were synthesized to capture its targets, and dual luciferase reporter system was used to evaluate its activity of calcium. It was found that it could make calcium overload by regulating transient receptor potential cation channel, subfamily M, member 8 (TrpM8). Then, the results of mass spectrometry imaging showed that the accumulation of ferulic acid in the heart was significantly increased by borneol, and the relaxation rate of rat thoracic aorta was enhanced obviously. In summary, the borneol in Suxiaojiuxin pills can expand cell space and increase intestinal permeability by acting on TrpM8, thus promoting the intestinal absorption, tissue distribution and target organ enrichment of drugs.

Study on rat intestinal absorption characteristics of total flavonoids from Coreopsis tinctoria / 中国中药杂志

The rat everted intestinal sac model was adopted to investigate the absorption of total flavonoids from Coreopsis tinctoria in different intestinal segments. Cyaniding-3-O-β-D-glucoside, chlorogenic acid, flavanomarein, quercetagetin-7-O-β-D-glucoside, iso-okanin, marein and 3,5-dicaffeoylquinic acid which as the major chemical components of total flavonoids from C. tinctoria were selec-ted as the study objects to evaluate the absorption characteristics of each component in different intestinal segments. The results showed that the absorption of seven components of total flavonoids at different intestinal segments was in consistent with zero order absorption rate. The K_a of chlorogenic acid, flavanomarein, quercetagetin-7-O-β-D-glucoside, isookanin and 3,5-dicaffeoylquinic acid increased with increasing of concentration of total flavonoids(P<0.05), indicating that the intestinal absorption of these five components was passive transport. The K_a of cyaniding-3-O-β-D-glucoside and marein showed a weak concentration dependence, suggesting that the absorption of them may be an positive and passive co-existing mode. The result of absorption in different intestinal segments showed that cyaniding-3-O-β-D-glucoside, chlorogenic acid, flavanomarein, quercetagetin-7-O-β-D-glucoside, marein and 3,5-dicaffeoylquinic acid were mainly absorbed in ileum, while isookanin was mainly absorbed in jejunum. The total flavonoids of C. tinctoria are selectively absorbed in intestinal tract, the rat everted intestinal sac model can be used to evaluate the multi-component intestinal absorption characteristics of total flavonoids from C. tinctoria.

Intestinal absorption characteristics of Polygonum orientale extract in normal and isoproterenol-induced myocardial ischemia model rats via everted intestinal sac models / 中国中药杂志

The present study is to investigate the absorption characteristics of the main components in Polygonum orientale extract in normal and isoproterenol-induced myocardial ischemia model rats with everted intestinal sac models. Intestinal sac fluid samples were collected in different part of intestine(duodenum, jejunum, ileum, colon) at different time after administration of different concentration of P. orientale extract(5.0,10.0, 20.0 mg·mL~(-1)). An UPLC-TQD method was employed for the determination of six components including orientin, isoorientin, vitexin, protocatechuic acid, kaempferol-3-O-β-D-glucoside and quercitrin in the intestinal sac samples. The absorption rate and cumulative absorption were calculated to analyze the intestinal absorption characteristics of six components in normal and myocardial ischemia model rats. The P-glycoprotein(P-gp) inhibitor was applied to investigate influence of intestinal absorption of six components in P. orientale extract. The results showed that the main absorption sites were concentrated on the duodenum at low concentration, while they were the colon at the medium concentration and the ileum at high concentration in control groups. In the condition of myocardial ischemia model, the main absorption sites focus on the ileum and jejunum at low concentration; the main absorption sites were in the ileum at the medium concentration and main absorption sites were the duodenum and ileum at high concentration. Compared with the normal group, the absorption rate and cumulative absorption of the six components significantly decreased in the model group. P-gp inhibitor markedly increased the absorption rate and cumulative absorption of six components in the model group, inferring that the 6 components may be the substrates of P-gp, and the mechanism needs further study. In this study, it is revealed that the six components of P. orientale extract can be absorbed into the intestinal sac, and it is an effective method to assess the intestinal absorption characteristics of P. orientale extract through everted intestinal sac model, providing data support for the clinical application and further development of P. orientale.

Study on Absorption Characteristics of Gastrodia elata Powder with Different Particle Sizes Based on Rat Everted Intestinal Sac Model in vitro / 中国药房

OBJECTIVE：To compar e the absorpt ion characteristics of gastrodin ，parishin A ，parishin B and parishin C of Gastrodia elata powder，and to explore the effect of particle size on intestinal absorption of above components. METHODS ：Based on everted intestinal sac model ，using accumulative absorption amount （Q）and absorption rate constant （Ka）as indexes ，UPLC-MS/MS method was used to determine the absorption of gastrodin ，parishin A ，parishin B and parishin C from different doses （2.5，5，10 g/L） of G. elata powder with different particle sizes （fine powder 146 μm，superfine powder 52 μm，ultrafine powder 37 μm）in different segments（duodenum，jejunum，ileum and colon ）. RESULTS ：Q and Ka of gastrodin and parishin B （intestinal segment ），Q（colon） and Ka（ileum and colon ）of parishin C in 2.5 g/L G. elata superfine powder ；Q and Ka of gastrodin （intestinal segment ），Q and Ka of parishin B （duodenum，jejunum，ileum）and Ka of parishin C （colon）in 2.5 g/L G. elata ultrafine powder ；Q of gastrodin （duodenum），Q of parishin A and parishin B （intestinal segment ）and Q of parishin C （duodenum，jejunum）in 5 g/L G. elata superfine powder ；Q（duodenum jejunum ，colon）and Ka（intestinal segment ）of gastrodin ，Q of parishin B （duodenum，ileum and colon）and Q of parishin C （duodenum，ileum）in 5 g/L G. elata ultrafine powder ；Q and Ka of parishin B （jejunum，ileum），Q of parishin C （jejunum，ileum）in 10 g/L G. elata superfine powder as well as Q（colon）and Ka（duodenum）of gastrodin ，Q （duodenum，ileum，colon）and Ka（duodenum，colon）of parishin B ，Q（duodenum，ileum）and Ka（duodenum）of parishin C in 10 g/L G. elata ultrafine powder were all increased significantly ，compared with the same dose of G. elata fine powder （P＜0.05 or P＜0.01）. Ka of parishin A （jejunum）and Q of parishin C （duodenum）in 2.5 g/L G. elata superfine powder ；Ka of parishin A （jejunum，ileum）， Q and Ka of parishin C （duodenum，jejunum）in 2.5 g/L G. elata ultrafine powder ；Ka of gastrodin （jejunum，ileum and colon ），Ka of parishin A （colon），Ka of parishin B （ileum）and Ka of parishin C （jejunum，ileum）in 5 g/L G. elata superfine powder ；Ka of gastrodin and parishin C （jejunum，ileum and colon ），Q（jejunum，colon）and Ka（colon）of parishin A ，Ka of parishin B （jejunum，ileum）in 5 g/L G. elata ultrafine powder ；Q and Ka of parishin A （ileum）in 10 g/L G. elata superfine powder ；Q（duodenum）and Ka（jejunum） of parishin A ，Ka of parishin C （jejunum）in 10 g/L G. elata ultrafine powder were decreased significantly ，compared with the same dose of G. elata fine powder （P＜0.05 or P＜0.01）. Q of gastrodin （colon），Q（colon）and Ka（ileum，colon）of parishin A ，Q and Ka of parishin B （jejunum，colon），Q and Ka of parishin C （ileum，colon）in 2.5 g/L G. elata fine powder ；Q and Ka of gastrodin （colon），Q（ileum，colon）and Ka（jejunum，ileum，colon）of parishin A ，Ka of parishin C （colon）in 2.5 g/L G. elata superfine powder；Q（colon）and Ka（jejunum，ileum，colon）of parishin A and C ，Q and Ka（ileum，colon）of parishin B in 2.5 g/L G. elata ultrafine powder ；Q and Ka of gastrodin ，parishin A and C （colon），Ka of parishin B （colon）in 5 g/L G. elata fine powder ；Q and Ka of gastrodin and parishin A （colon），Q and Ka of parishin C （jejunum，ileum，colon）in 5 g/L G. elata superfine powder ；Q and Ka of gastrodin（ileum，colon），Q of parishin A （jejunum，ileum，colon），Q and Ka of parishin B （jejunum，colon），Q（jejunum，colon） and Ka（jejunum，ileum，colon）of parishin C in 5 g/L G. elata ultrafine powder ；Q of gastrodin （colon），Q and Ka of parishin A ，B and C （jejunum，ileum，colon）in 10 g/L G. el ata fine powder ；Q of gastrodin （colon），Q and Ka of parishin A and C （jejunum， ileum，colon），Q and Ka of parishin B （colon）in 10 g/L G. elata superfine powder ；Q（colon）and Ka（jejunum，ileum，colon）of gastrodin，Q and Ka of parishin A and C （jejunum，ileum，colon），Q（jejunum，ileum，colon）and Ka（ileum，colon）of parishin B in 10 g/L G. elata ultrafine powder were decreased significantly ，compared with duodeum of the same group （P＜0.05）. Q and Ka of gastrodin（jejunum）in 2.5 g/L G. elata superfine pow

Effect of Berbamine Hydrochloride on Intestinal Absorption Characteristics of Berberine Hydrochloride by Rat Everted Intestinal Sac Model / 中国实验方剂学杂志

Objective: To investigate the effect of berbamine hydrochloride on the absorption characteristics of berberine hydrochloride in different intestinal segments of rats in normal environment and high calcium environment. Method: Taking rat everted intestinal sac model,the content of berberine hydrochloride in absorbent solution of everted intestinal sac from different compatibility groups was determined by HPLC,and the uptake per unit area in different groups was analyzed by One-way ANOVA. Result: Compared with the normal J70 group(in normal environment,the concentration of berberine hydrochloride was 70 mg·L-1) at the same time point,the uptake per unit area of the normal J70+Ver100 group(in normal environment,the concentration of berberine hydrochloride was 70 mg·L-1,adding verapamil hydrochloride to a concentration of 100 mg·L-1) was significantly increased in the ileum(P-1,adding berbamine hydrochloride to a concentration of 35 mg·L-1) were significantly increased in the duodenum(P-1,adding berbamine hydrochloride to a concentration of 70 mg·L-1) were significantly increased in the ileum(PConclusion: Berbamine hydrochloride can promote the absorption of berberine hydrochloride in intestine to a certain extent,especially in the high calcium environment.

Investigation on intestinal absorption ingredients and their absorption characteristics in Pterocephali Herba by everted intestinal sac method / 中国中药杂志

The intestinal absorption characteristics of ten iridoid glycosides and phenolic acids in the Pterocephali Herba were evaluated via rat intestinal valgus model. The intestinal sac fluids at different time after administration of high,medium and low concentrations of Pterocephali Herba extract were collected and ten chemical components in fluid samples were detected by UPLC-PDA. Accumulative absorbed doses( Q) and absorption rate constants( Ka) of ten chemical constituents were calculated,while proportions between Pterocephali Herba extract and intestinal absorption liquid were compared. The results showed that the intestinal absorption of 10 chemical components was linear absorption( R2>0. 9) at different concentrations,which accorded with the zero-order absorption rate. The absorption rate constant was related to the concentration of the drug and the intestinal site,which indicated that intestinal adsorption mechanism of the components were passive diffusion and active transport. Proportions of chemical constituents in intestinal sac fluid were different from those in Pterocephali Herba extract. Therefore,those ten chemical components in Pterocephali Herba extract can be absorbed in whole intestine. Everted intestinal sac model can be used to evaluate intestinal absorption characteristics of ingredients in Pterocephali Herba extract effectively.

Advances in models for predicting drug intestinal permeability / 药学学报

Intestinal permeability is one of key factors determing absorption of oral drug products. It is a big challenge to assess permeability of compounds with high accuracy and high efficacy during research and development process. In this review, the principles, strengths, weaknesses and advances of common intestinal permeability models are summarized, with focus on Ussing chamber and parallel artificial membrane permeability assay. In addition, future trends of permeability models are briefly discussed. This review may provide a reference to accessing permeability of lead compounds.

Absorption of Inula cappa extract based on everted intestinal sac method / 中国中药杂志

To investigate the absorptive characteristics of Inula cappa extract based on the rat everted intestinal sac method . Nine representative ingredients in I. cappa extract were selected as the study objects. An UPLC-MS/MS method was established to determine and detect their cumulative absorption amount for expounding the absorptive characteristics of ingredients in different intestinal sections. According to the results， the transport mechanism of 8 compounds showed passive diffusion by the reverted gut sac method. And scopolin was actively transported in the intestine. The best absorption site of chlorogenic acid was duodenum. The best absorption site of cryptochlorogenic acid， 1，3--dicaffeoylquinic acid， luteolin-7-glucoside and 3，4--dicaffeoylquinic acid were jejunum. The best absorption site of neochlorogenic acid， scopolin， 4，5--dicaffeoylquinic acid and 3，5--dicaffeoylquinic acid was ileum. The absorption of all the compounds was affected by pH and bile. All of the nine ingredients in I. cappa extract could be absorbed in intestines， but with differences in the absorption rate， the best absorptive site and mechanism， indicating that the intestinal absorption of I. cappa extract was selective.

Intestinal absorptive characteristics of ingredients from ethanol extracts of Gandou decoction by rat everted intestinal sac models / 中国中药杂志

To study the intestinal absorptive characteristics of the ethanol extracts from Gandou decoction(GDD), everted intestinal sac models were used. The six representative ingredients (berberine hydrochloride, quercetin, kaempferide, rhein, chrysophanol, and aloe emodin) of GDD, were selected as the experimental targets to investigate the absorptive characteristics of various ingredients in different intestinal sections. The results showed that all six ingredients from GDD were detected in the intestinal sac, three active ingredients (berberine hydrochloride, quercetin, kaempferide) in high, medium and low doses had linear absorption properties in the small intestine segment, consistent with zero-order absorption rate; in addition, the absorption rate constant (Ka) of three components in jejunum and ileum were increased with the increase of the concentration of GDD (P<0.05), consistent with passive absorption. However, the Ka of rhein in jejunum and ileum showed little difference with the increase of dosage, suggesting a possibility of active transport mechanism. Chrysophanol and aloe-emodin were poorly absorbed in the two segments, which had not been detected in the previous time. The results suggested that the components of GDD were selectively absorbed in the intestinal sac, and the absorption characteristic of the ingredients were not exactly similar.

Absorption characteristics of alkaloids in Fuzheng Xiaozheng Fang by rat everted intestinal sac models / 中国中药杂志

Everted intestinal sac models were used to investigate the intestinal absorption of the 4 alkaloids(berberine, palmatine, coptisine, and epiberberine) in Fuzheng Xiaozheng Fang(FZ) at different intestine segments. The absorption parameters of each component were calculated; SPSS 20.0 software was used to analyze the data and evaluate the absorption characteristics at different intestinal segments. The results showed that all the four active ingredients conformed to zero-order absorption rate. There was significant difference in absorption rate constant (Ka) between the four ingredients at low dose and medium and high dose groups(P<0.05), but there was no significant difference in Ka between medium dose and high dose. The absorption mechanization of four ingredients presented two absorption manners： positive diffusion and passive absorption. The absorptive amount of 4 alkaloids in ileum was slightly greater than that of jejunum, but no significant differences were observed, which indicated that these four alkaloids had no specific absorption windows in intestinal segment.

Analysis on intestinal absorption of paeoniflorin lipid liquid crystalline nanoparticles via everted intestinal sacs / 中国中药杂志

To study the absorption kinetics of paeoniflorin lipid liquid crystalline nanoparticles (Pae-LLCN) in different intestinal segments of rats and compare them with paeoniflorin(Pae) solution. Rat everted gut sac models were adopted for intestinal absorption test, and Pae content was determined by HPLC method to study the absorption characteristics of Pae-LLCN in rat duodenum, jejunum, ileum and colon, and investigate the effects of different drug concentrations on intestinal absorption. Results showed that Pae-LLCN and Pae were well absorbed at different intestine segments and different concentrations. The absorption constant Ka was increased with the increasing of the drug concentration, indicating possible passive absorption. The accumulative absorption volume Q and absorption constant Ka of Pae-LLCN were higher than those of Pae at each intestinal segment(P<0.05). The results revealed that Pae-LLCN and Pae could be well absorbed in whole intestinal segments and its mechanism may be passive absorption. LLCN can effectively improve the intestinal absorption of Pae.

Effects of Fufangbiejiaruangan tablet compound prescription on intestinal absorption of paeoniflorin / 中国药学杂志

OBJECTIVE: To study the intestinal absorption characteristics of three components (paeoniflorin, phillyrin, ginsen-osides Rg1) of Fufangbiejiaruangan tablets and the effects of prescription on the intestinal absorption of paeoniflorin. METHODS: Everted intestinal sac method was adopted to mimic the intestinal absorption process of Fufangbiejiaruangan tablets extract at three concentrations. The intestinal absorption mechanisms of paeoniflorin, phillyrin and ginsenoside Rg1 were studied. HPLC assay was used to determine the three components and the time-accumulative absorption curves were drawn to compare the absorption characteristics of paeoniflorin in the prescription preparation and paeoniflorin solution. RESULTS: The absorption of the three components was linear at different intestinal segments and doses, and the correlation coefficients of the regression equations were all more than 0.9 (r≤0.9), which were consistent with zero order rate process. The Ka(s) of the components increased along with the increasing dosage, which indicated passive absorption. The cumulative absorption rate of paeoniflorin in Fufangbiejiaruangan tablets was better than one-component solution. CONCLUSION: The compatibility of Fufangbiejiaruangan tablets is beneficial to paeoniflorin absorption and ginsenoside Rg1 may be the indicator of the quality standard of Fufangbiejiaruangan tablets.

Correlation between absorption ingredients in Wuzhuyu Decoction and uptake amount in everted intestinal sac / 中草药

Objective: To explore the influence of the contents of nine ingredients in Wuzhuyu decoction on its own uptake amount into the everted intestinal sac, in order to blend Wuzhuyu decoction samples to improve the index of migraine model rats. Methods: The everted intestinal sac model was established to determine the absorption samples of 10 kinds of Wuzhuyu decoction. HPLC-DAD method was used to analyze the contents of nine ingredients in Wuzhuyu decoction and absorption samples quantitatively and semi-quantitatively. The partial least squares regression method was used to correlate the contents in the decoction and the total absorption quantity of nine ingredients. Results: In the experimental concentration range, the higher the concentration of limocitrin-3-O-β-D-glucoside, ginsenoside Rg1, 6-gingerol, and ruteavin in the decoction were, the more they were absorbed into the intestine sac, while ginsenosides Re, Rb1, limonin, evodiamine, and rutaecarpine were contrary. The interaction of different ingredients on each other's absorption was complicated. Conclusion: The above relationship should be considered to obtain the satisfactory samples of Wuzhuyu decoction.