Intestinal Absorption Mechanisms of Five Flavonoids from Malus hupehensis (Pamp.) Rehd. Extracts in Situ Single-Pass Intestinal Perfusion and in Vitro Caco-2 Cell Model

Abstract Background: Previous studies have shown that Malus hupehensis (Pamp.) Rehd. extracts have anti-oxidant, anti-aging and other effects, its bioavailability is low, however its absorption mechanism is still unclear. To investigate the absorption properties of hyperin, quercitrin, phloridzin, quercetin, and phloretin in total flavonoids of Malus hupehensis (Pamp.) Rehd. Extracts. Methods: In situ single-pass intestinal perfusion model and in vitro Caco-2 cell model were used in this study. The effects of concentration of the extract, administration time, temperature, different intestinal segments, paracellular pathway were analyzed, and the effect of efflux inhibitors, such as the P-gp inhibitor verapamil, the multidrug resistance protein2 (MRP2) inhibitor indomethacin, the breast cancer resistance protein (BCRP) inhibitor reserpine, on the transport were evaluated. As well as EDTA, a tight junction regulator, was studied.Results: The results indicated that the jejunum was the optimal absorption intestine segment of quercitrin, phloridzin, and phloretin. And the greatest absorption intestine segment of quercetin was ileum. Furthermore, it was found that the absorption mechanisms of phloridzin in extract was involved in passive diffusion and the mediation of P-gp and MRP2 should not be neglected. The absorption mechanisms of quercetin and phloretin from extract involved active transport and were accompanied by the participation of efflux transporters, such as P-gp, MRP2 and BCRP. And also the paracellular pathway was involved in hyperin and quercitrin. Conclusion: The absorption mechanisms of five flavonoids from Malus hupehensis (Pamp.) Rehd. extract are related to the concentration of the drugs, intestinal segments, and efflux protein.

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Intestinal absorption mechanisms of araloside A in situ single-pass intestinal perfusion and in vitro Caco-2 cell model

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2018.07.117 ◽

2018 ◽

Vol 106 ◽

pp. 1563-1569 ◽

Cited By ~ 8

Author(s):

Hui Yang ◽

Bingtao Zhai ◽

Yu Fan ◽

Jing Wang ◽

Jing Sun ◽

...

Keyword(s):

Intestinal Absorption ◽

Cell Model ◽

Intestinal Perfusion ◽

Single Pass

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Self-Emulsifying Drug Delivery System of Simvastatin: Formulation Development, Optimization by Box- Behnken Design, In-Vitro and In-Situ Single-Pass Intestinal Perfusion (SPIP) Studies

Recent Patents on Drug Delivery & Formulation ◽

10.2174/1872211312666181022150435 ◽

2019 ◽

Vol 12 (3) ◽

pp. 199-211 ◽

Cited By ~ 1

Author(s):

Madhu Verma ◽

Arun Nanda ◽

Yatendra Kumar

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Intestinal Perfusion ◽

Formulation Development ◽

Box Behnken Design ◽

Single Pass

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Intestinal transport of HDND-7, a novel hesperetin derivative, in in vitro MDCK cell and in situ single-pass intestinal perfusion models

Xenobiotica ◽

10.1080/00498254.2016.1214987 ◽

2016 ◽

Vol 47 (8) ◽

pp. 719-730 ◽

Cited By ~ 2

Author(s):

Ruonan Chen ◽

Lan Li ◽

Chenlin Shen ◽

Cheng Huang ◽

Taotao Ma ◽

...

Keyword(s):

Mdck Cell ◽

Intestinal Transport ◽

Intestinal Perfusion ◽

Single Pass

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Preparation of Puerarin Chitosan Oral Nanoparticles by Ionic Gelation Method and Its Related Kinetics

Pharmaceutics ◽

10.3390/pharmaceutics12030216 ◽

2020 ◽

Vol 12 (3) ◽

pp. 216 ◽

Cited By ~ 2

Author(s):

Jie Yan ◽

Zhi-Yu Guan ◽

Wei-Feng Zhu ◽

Ling-Yun Zhong ◽

Zhuo-Qi Qiu ◽

...

Keyword(s):

In Vitro Release ◽

Intestinal Perfusion ◽

Pharmacokinetic Studies ◽

Ultrasonic Power ◽

Ionic Gelation ◽

Single Pass ◽

Perfusion Model ◽

Vitro Release

In this paper, as an active ingredient, puerarin chitosan nanoparticles (Pur-CS/TPP-NPs) are prepared by an ionic gelation method. The chitosan (CS) concentration, pH of the CS solution, sodium tripolyphosphate (TPP) concentration, stirring speed, stirring time, ultrasonic power, and dosage are used as single factors for investigation, and the encapsulation efficiency, drug loading capacity, particle size, and polydispersity index (PDI) are used as indicators for investigation. The optimal prescription is determined using the Box–Behnken effect surface design method. The characterization of the best formulation, which is determined via an in vitro release assay and liquid chromatography/tandem mass spectrometry (LC-MS/MS) analysis methods, is used here for pharmacokinetic studies. An in situ single-pass intestinal perfusion model is used to investigate drug absorption in the intestine. After characterization, the morphologies of the nanoparticles are intact. It can be seen from the in vitro release experiments that the equation fitted by the nanoparticles is the Higuchi model, the nanoparticle release process is very stable and without sudden release, indicating that the nanoparticles are well-released in vitro. The pharmacokinetic results and the in situ single-pass intestinal perfusion model study show that the bioavailability and absorption of Pur-CS/TPP-NPs were significantly higher than Pur. Thus, all the results show that the prepared nanoparticles can significantly improve the bioavailability of Pur, and we hope to lay the foundation for the development of new products of Pur.

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Effect of Berbamine Hydrochloride on Absorption Parameters of Berberine Hydrochloride Based on in Situ Single-Pass Intestinal Perfusion System in the Rat

10.21203/rs.3.rs-73165/v1 ◽

2020 ◽

Author(s):

Jie Gao ◽

Hui Feng ◽

Ruohong Bi ◽

Lin Pan ◽

Yi Shi ◽

...

Keyword(s):

Mass Concentration ◽

Concentration Ratio ◽

Calcium Influx ◽

Intestinal Perfusion ◽

Control Group ◽

Drug Bioavailability ◽

Berberine Hydrochloride ◽

Single Pass ◽

Intestinal Segments

Abstract Background:Berberine is a kind of chemical that has obvious effects of lowering blood sugar, lowering blood lipid. The high toxicity of intravenous administration of berberine hydrochloride(BBH), it is only used for oral administration in clinic,but it only about 10% bioavailability. P-glycoprotein (P-gp) efflux function affects drug bioavailability，BBH is the substrate of P-gp, furthermore the recognized inhibitor of P-gp (such as verapamil) can promote the absorption of BBH. Berbamine hydrochloride(BAH) had a significant inhibitory effect on calcium influx after activation of receptor regulated calcium channels, and the calcium antagonistic effect of BAH is similar to that of verapamil. Methods: Based on the in situ single-pass intestinal perfusion method, this article compares the absorption of the BAH ratio group and the BBH control group in different intestinal segments,and investigates their absorption parameters. Results:The results of in situ single-pass intestinal perfusion showed that the absorption rate constant (Ka), effective permeability coefficient (Papp) , and cumulative absorption per unit area per hour (Q) in the duodenum, jejunum and ileum of the BAH ratio group were greater than those of the BBH control group, which means that the absorption of BBH in the ratio group increased in various intestinal segments, and the absorption of BBH in the small intestine was promoted by BAH.In addition,the mass concentration ratio of BBH and BAH group is B40:A50, B30:A20，where BBH is better absorbed than other groups. Conclusions:BAH can indeed promote the absorption of BBH,and improve the biological utilization of BBH degree.The mass concentration ratio of BBH and BAH group is B40:A50, B30:A20，where BBH is better absorbed than other groups, providing a basis for the development and research of the subsequent preparation of BBH.

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Intestinal absorption of forsythoside A in in situ single-pass intestinal perfusion and in vitro Caco-2 cell models

Acta Pharmacologica Sinica ◽

10.1038/aps.2012.58 ◽

2012 ◽

Vol 33 (8) ◽

pp. 1069-1079 ◽

Cited By ~ 19

Author(s):

Wei Zhou ◽

Liu-qing Di ◽

Juan Wang ◽

Jin-jun Shan ◽

Shi-jia Liu ◽

...

Keyword(s):

Intestinal Absorption ◽

Intestinal Perfusion ◽

Cell Models ◽

Single Pass

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Absorption Properties of Luteolin and Apigenin in Genkwa Flos Using In Situ Single-Pass Intestinal Perfusion System in the Rat

The American Journal of Chinese Medicine ◽

10.1142/s0192415x1750094x ◽

2017 ◽

Vol 45 (08) ◽

pp. 1745-1759 ◽

Cited By ~ 6

Author(s):

Xin He ◽

Zi-Jing Song ◽

Cui-Ping Jiang ◽

Chun-Feng Zhang

Keyword(s):

Small Intestine ◽

Intestinal Absorption ◽

Rat Model ◽

Clinical Effectiveness ◽

Intestinal Perfusion ◽

Flower Bud ◽

Transport Pathway ◽

Absorption Enhancers ◽

Single Pass

The flower bud of Daphne genkwa (Genkwa Flos) is a commonly used herbal medicine in Asian countries. Luteolin and apigenin are two recognized active flavonoids in Genkwa Flos. The aim of this study was to investigate the intestinal absorption mechanisms of Genkwa Flos flavonoids using in situ single-pass intestinal perfusion rat model. Using HPLC, we determined its major effective flavonoids luteolin, apigenin, as well as, hydroxygenkwanin and genkwanin in biological samples. The intestinal absorption mechanisms of the total flavonoids in Genkwa Flos (TFG) were investigated using in situ single-pass intestinal perfusion rat model. Comparing the TFG absorption rate in different intestinal segments, data showed that the small intestine absorption was significantly higher than that of the colon ([Formula: see text]). Compared with duodenum and ileum, the jejunum was the best small intestinal site for TFG absorption. The high TFG concentration (61.48[Formula: see text][Formula: see text]g/ml) yielded the highest permeability ([Formula: see text]). Subsequently, three membrane protein inhibitors (verapamil, pantoprazole and probenecid) were used to explore the TFG absorption pathways. Data showed probenecid, a multidrug resistance protein (or MRP) inhibitor, effectively enhanced the TFG absorption ([Formula: see text]). Furthermore, by comparing commonly used natural absorption enhancers on TFG, it was observed that camphor was the most effective. In Situ single-pass intestinal perfusion experiment shows that TFG absorption is much higher in the small intestine than in the colon, and the TFG is absorbed mainly via an active transport pathway with MRP-mediated efflux mechanism. Camphor obviously enhanced the TFG absorption, and this could be an effective TFG formulation preparation method to increase clinical effectiveness after Genkwa Flos administration. Our study elucidated the TFG absorption mechanisms, and provided new information for its formulation preparation.

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