Mechanistic studies of the transport of peimine in the Caco-2 cell model

Published on Mar 1, 2016in Acta Pharmaceutica Sinica B5.808
· DOI :10.1016/j.apsb.2016.01.006
Lihua Chen3
Estimated H-index: 3
(JUTCM: Jiangxi University of Traditional Chinese Medicine),
Xue-Ping Lu1
Estimated H-index: 1
(JUTCM: Jiangxi University of Traditional Chinese Medicine)
+ 4 AuthorsWei-feng Zhu4
Estimated H-index: 4
(JUTCM: Jiangxi University of Traditional Chinese Medicine)
Fritillaria thunbergii Miq. has been widely used in traditional Chinese medicine for its expectorant, antitussive, antiinflammatory and analgesic properties. Moreover, modern pharmacological studies have demonstrated that F. thunbergii Miq. has efficacy in the treatment of leukemia and cancers of the liver and cervix. Although the alkaloid, peimine, is largely responsible for these pharmacological effects, it has very low oral bioavailability. The aim of this study was to investigate the intestinal absorption of peimine in Caco-2 cell monolayers. Having demonstrated that peimine is non-toxic to Caco-2 cells at concentrations <200 μmol/L, the effect of peimine concentration, pH, temperature, efflux transport protein inhibitors and EDTA-Na2 on peimine transport were studied. The results show that peimine transport is concentration-dependent; that at pH 6.0 and 7.4, the Papp(AP-BL) of peimine is not significantly different but the Papp(BL-AP)) is; that both Papp(AP-BL) and Papp(BL-AP) at 4 °C are significantly higher than their corresponding values at 37 °C; that the P-glycoprotein (P-gp) inhibitors, verapamil and cyclosporin A, increase absorption of peimine; and that EDTA-Na2 has no discernible effect. In summary, the results demonstrate that the intestinal absorption of peimine across Caco-2 cell monolayers involves active transport and that peimine is a substrate of P-gp.
  • References (21)
  • Citations (12)
📖 Papers frequently viewed together
50 Citations
9 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Sohee Kim (DCU: Catholic University of Daegu)H-Index: 1
#2Beom Soo Shin (DCU: Catholic University of Daegu)H-Index: 23
Last. Eunsook Ma (DCU: Catholic University of Daegu)H-Index: 9
view all 3 authors...
Twelve N-substituted anthranilamide esters (1–5, 8, 9, 12, 13, and 15–17) were synthesized and evaluated for their ability to inhibit the in vitro aggregation by washed human platelets induced by adenosine 5′-diphosphate (10 μM). The antiplatelet activity of dl-n-butyl 5-hydroxy-N-(2-phenoxypropionyl)anthranilate (9, IC50 = 10.5 μM) was most active among the tested compounds and ethyl ester 8 (IC50 = 11.2 μM) showed the second most activity. dl-Ethyl and dl-n-butyl 5-(p-toluenesulfonyloxy)-N-(2-...
1 CitationsSource
#1Yi Zheng (CPU: China Pharmaceutical University)H-Index: 2
#2Leslie Z. Benet (UCSF: University of California, San Francisco)H-Index: 79
Last. Xijing Chen (CPU: China Pharmaceutical University)H-Index: 16
view all 4 authors...
Purpose Recent controversial publications, citing studies purporting to show that P-gp mediates the transport of propranolol, proposed that passive biological membrane transport is negligible. Based on the BDDCS, the extensively metabolized-highly permeable-highly soluble BDDCS class 1 drug, propranolol, shows a high passive permeability at concentrations unrestricted by solubility that can overwhelm any potential transporter effects. Here we reinvestigate the effects of passive diffusion and ca...
13 CitationsSource
#1Yan ChenH-Index: 15
#2Ying WangH-Index: 3
Last. Congyan LiuH-Index: 9
view all 6 authors...
Epimedium spp. is commonly used in Traditional Chinese Medicine. Epimedins A, B, and C are three major bioactive flavonoids found in Epimedium spp. that share similar chemical structures. In this study, the intestinal absorption mechanism of these three compounds was investigated using the Caco-2 cell monolayer model in both the apical-to-basolateral (A-B) and the basolateral-to-apical (B-A) direction. The absorption permeability (PAB) of epimedins A, B, and C were extremely low and increased as...
10 CitationsSource
#1Guan ZyH-Index: 1
#2Zhang LhH-Index: 1
Last. Hongning LiuH-Index: 4
view all 5 authors...
3 Citations
#1Meng-Liang Zhu (JUTCM: Jiangxi University of Traditional Chinese Medicine)H-Index: 1
#2Xin-Li Liang (JUTCM: Jiangxi University of Traditional Chinese Medicine)H-Index: 9
Last. Yun Luo (JUTCM: Jiangxi University of Traditional Chinese Medicine)H-Index: 2
view all 8 authors...
Abstract Ethnopharmacological relevance Angelicae Dahurica (Hoffm.) Benth. & Hook. f. ex Franch. & Sav combined with Radix Scutellariae baicalensis Georgi has been widely used in traditional Chinese medicine (TCM) as an antipyretic analgesic and anti-inflammatory drug. Modern pharmacological studies have demonstrated that the compatible application of these two drugs is an effective treatment for hepatitis. A previous study indicated that a Radix Angelicae Dahuricae extract enhanced the intestin...
20 CitationsSource
#1Cuiping YangH-Index: 6
#2Zheng LiH-Index: 3
Last. Zhenqing ZhangH-Index: 10
view all 6 authors...
Abstract Aconitine (AC) is a highly toxic compound present in plants of the genus Aconitum . The transcellular transport mechanism of AC was investigated using Caco-2 cells. The flux of AC was time- and concentration-dependent in both apical-to-basolateral and the reverse direction. The efflux of AC was more than two-fold that in the opposite direction. The influx of AC was temperature-, pH- and Na + -dependent. Glucose markedly decreased the absorption of AC. However, the efflux of AC was tempe...
20 CitationsSource
#1Ling Ye (Southern Medical University)H-Index: 13
#2Xiaoshan Yang (Southern Medical University)H-Index: 6
Last. Zhongqiu Liu (Southern Medical University)H-Index: 22
view all 9 authors...
Abstract Aconitum alkaloids including aconitine (AC), mesaconitine (MA), hypaconitine (HA), are highly toxic. Their hydrolysates, such as benzoylaconine (BAC), benzoylmesaconine (BMA), benzoylhypaconine (BHA), aconine, and mesaconine, are considerably less toxic. Efflux transporters, including P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-associated protein isoform 2 (MRP2), act as a first line of defence and play key roles in toxicity prevention. The a...
41 CitationsSource
#1Joana M. Planas (University of Barcelona)H-Index: 23
#2Irene Alfaras (University of Barcelona)H-Index: 6
Last. M. Emília Juan (University of Barcelona)H-Index: 19
view all 4 authors...
The ABC proteins are a family of membrane transporters that mediates the extrusion from cells of a wide variety of structurally unrelated substrates. The current review focuses on the role of these efflux pumps located in the intestine on the low oral bioavailability of trans-resveratrol. The enterocytes hold in the apical membrane three transporters, namely, P-glycoprotein (P-gp), multidrug resistance associated protein 2 (MRP2) and breast cancer resistance protein (BCRP), whereas the basolater...
63 CitationsSource
#1Ye Tian (ZJU: Zhejiang University)H-Index: 1
#2Ying He (ZJU: Zhejiang University)H-Index: 1
Last. Su Zeng (ZJU: Zhejiang University)H-Index: 30
view all 5 authors...
Abstract This study aimed to determine the transepithelial transport characteristics of chiral drug enantiomers across Caco-2 cell monolayers, a model of human intestinal epithelial membrane. Six chiral aryloxy enantiomers (atenolol, sotalol, celiprolol, carvedilol, metoprolol and propafenone) were tested in bi-directional transport studies. The separation and quantitation of these enantiomers were performed by reversed-phase high-performance liquid chromatography (RP-HPLC) using 2, 3, 4, 6-tetr...
7 CitationsSource
#1Chenrui Li (CUHK: The Chinese University of Hong Kong)H-Index: 8
#2Li Zhang (CUHK: The Chinese University of Hong Kong)H-Index: 17
Last. Zhong Zuo (CUHK: The Chinese University of Hong Kong)H-Index: 33
view all 6 authors...
Radix Scutellariae is a commonly used herbal medicine. Baicalein, wogonin, and oroxylin A are three major bioactive flavones in Radix Scutellariae and share similar chemical structures. The intestinal absorption and disposition of baicalein have been systematically investigated by our group before. In this study, the intestinal absorption and disposition of wogonin and oroxylin A were further explored and compared with the profiles of baicalein to find potential structure–activity relationship. ...
31 CitationsSource
Cited By12
#1K. Gianni de Carvalho (CONICET: National Scientific and Technical Research Council)
#2J.E. Gómez (CONICET: National Scientific and Technical Research Council)
Last. Verónica Leticia Colin (CONICET: National Scientific and Technical Research Council)H-Index: 10
view all 8 authors...
Abstract In the present work, the production of bioemulsifier (BE) by a lactic acid bacterium (LAB) grown at 25 °C in lactic whey-based media for 24 h was evaluated. Maximum production was detected in a medium containing yeast extract, peptone and lactic whey (LAPLW medium), with a yield of 270 mg L−1. The BE proved to be more innocuous for Caco-2 cells, used as a toxicological indicator, than the non-ionic surfactant Triton X-100. In addition, the microbial product presented higher stability to...
#1Pratyusa Sahoo (UM: University of Malaya)H-Index: 1
#2Kok Hoong Leong (UM: University of Malaya)H-Index: 10
Last. Lip Yong Chung (UM: University of Malaya)H-Index: 19
view all 6 authors...
Abstract We previously reported that insulin-entrapped chitosan complexed carboxymethylated iota-carrageenan (CS/CMCi) particles exhibit pH-responsive swelling behavior. However, the particles’ stability in the enzymatic gastrointestinal environment, their drug permeability mechanism, and related in vivo studies have not been discussed to date. In this study, we investigated the stability, muco-adhesiveness, transport mechanism and in vivo assessment of the particles. The particles retained thei...
#1Yulin Wang (Dalian Medical University)
#2Yongjie Li (Dalian Medical University)
Last. Thomas Efferth (University of Mainz)H-Index: 67
view all 4 authors...
Abstract Background Artemisinin was isolated and identified in 1972, which was the starting point for a new era in antimalarial drug therapy. Furthermore, numerous studies have demonstrated that artemisinin and its derivatives exhibit considerable anticancer activity both in vitro, in vivo, and even in clinical Phase I/II trials. P-glycoprotein (P-gp) mediated multi-drug resistance (MDR) is one of the most serious causes of chemotherapy failure in cancer treatment. Interestingly, many artemisini...
#1Mariana de Oliveira Mauro (UNESP: Sao Paulo State University)H-Index: 11
#2R.A. De Grandis (UNESP: Sao Paulo State University)H-Index: 1
Last. N.V. de Moraes (UNESP: Sao Paulo State University)H-Index: 1
view all 8 authors...
Abstract Ethnopharmacological relevance Copaiba oleoresin has been used in folk medicine in the treatment of bronchitis, syphilis, skin diseases and ulcers due to its anti-inflammatory and antiseptic activities, but there is no information about major compounds oral absorption to support the traditional use. Aim of study Considering the potential of copalic (CA) and kaurenoic acid (KA) – major biological activity (in vitro) diterpenes found in the oleoresin, this study aimed to evaluate the inte...
1 CitationsSource
#1Mengshi Pan (CAU: China Agricultural University)
#2Yanjiao Huo (CAU: China Agricultural University)
Last. Bo Li (CAU: China Agricultural University)H-Index: 16
view all 6 authors...
Abstract Inhibiting low-density lipoprotein (LDL) oxidation and cellular lipid accumulation to reduce foam cell formation plays a key role in preventing atherosclerosis. Casein hydrolysate (66%
#1Gretta C. M’bitsi-Ibouily (University of the Witwatersrand)H-Index: 1
#2Thashree Marimuthu (University of the Witwatersrand)H-Index: 7
Last. Viness Pillay (University of the Witwatersrand)H-Index: 35
view all 8 authors...
Sulpiride (SPR) is a selective antagonist of central dopamine receptors but has limited clinical use due to its poor pharmacokinetics. The aim of this study was to investigate how metal ligation to SPR may improve its solubility, intestinal permeability and prolong its half-life. The synthesis and characterisation of ternary metal complexes [Ru(p -cymene)(L)(SPR)]PF6 (L1 = (R)-(+)-2-amino-3-phenyl-1-propanol, L2 = ethanolamine, L3 = (S)-(+)-2-amino-1-propanol, L4 = 3-amino-1-propanol, L5 = (S)-(...
#1Zhenhua Yin (Huanghe Science and Technology College)H-Index: 2
#2Juanjuan Zhang (Huanghe Science and Technology College)H-Index: 2
Last. Wenyi Kang (Huanghe Science and Technology College)H-Index: 8
view all 6 authors...
Verticine is the major bioactive constituent of Fritillaria as a kind of Traditional Chinese Medicine. Pharmacological researches have reported various benefits of verticine, including anticancer, anti-inflammatory, protecting against acute lung injury, tracheobronchial relaxation, antitussive, expectorant, sedative, and analgesic activities, in addition to inhibiting proliferation of cultured orbital fibroblast, angiotensin converting enzyme (ACE), and acetylcholinesterase (AChE) and inhibiting...
#2Liliana Beatriz Villegas (CONICET: National Scientific and Technical Research Council)H-Index: 7
Last. Verónica Leticia Colin (CONICET: National Scientific and Technical Research Council)H-Index: 10
view all 3 authors...
Abstract Vinasse is a waste material from distillery industries, which causes major environmental problems around the world. Argentina alone produces about 4 billion liters of vinasse annually; consequently, diverse biological eco-friendly treatments are evaluated for their ability to reduce the detrimental effects. The present study reports on the degradation of a 50% (v/v) local vinasse sample by an autochthonous fungus identified as Aspergillus sp. V1. The Bioprocess was conducted for 15 d at...
1 CitationsSource
#1Jieping LiH-Index: 1
#2Li YangH-Index: 1
Last. Guangsen Zhang (CSU: Central South University)H-Index: 1
view all 10 authors...
Recently, we found that berberine (BBR) exerts anti-acute myeloid leukemia activity, particularly toward high-risk and relapsed/refractory acute myeloid leukemia MV4-11 cells in vitro. However, the poor water solubility and low bioavailability observed with oral BBR administration has limited its clinical use. Therefore, we design and develop a novel oil-in-water self-nanoemulsifying system for BBR (BBR SNE) to improve oral bioavailability and enhance BBR efficacy against acute myeloid leukemia ...
7 CitationsSource
#1E Zhang (SDU: Shandong University)H-Index: 1
#2Fulong Chu (SDU: Shandong University)H-Index: 1
Last. Aiguo Ji (SDU: Shandong University)H-Index: 8
view all 6 authors...
1 CitationsSource