scholarly journals Inhibitory Effects of Daiokanzoto (Da-Huang-Gan-Cao-Tang) on P-Glycoprotein

2012 ◽  
Vol 2012 ◽  
pp. 1-7
Author(s):  
Yuka Watanabe ◽  
Nobutomo Ikarashi ◽  
Toshiyuki Satoh ◽  
Kiyomi Ito ◽  
Wataru Ochiai ◽  
...  
Keyword(s):  
Epigallocatechin Gallate ◽  
Licorice Root ◽  
Drug Transporter ◽  
Inhibitory Effects ◽  
Epicatechin Gallate ◽  
Glycoprotein P ◽  
Atpase Assay ◽  
P Glycoprotein ◽  
Herbal Ingredient

We have studied the effects of various Kampo medicines on P-glycoprotein (P-gp), a drug transporter,in vitro. The present study focused on Daiokanzoto (Da-Huang-Gan-Cao-Tang), which shows the most potent inhibitory effects on P-gp among the 50 Kampo medicines studied, and investigated the P-gp inhibitory effects of Daiokanzoto herbal ingredients (rhubarb and licorice root) and their components by an ATPase assay using human P-gp membrane. Both rhubarb and licorice root significantly inhibited ATPase activity, and the effects of rhubarb were more potent than those of licorice root. The content of rhubarb in Daiokanzoto is double that in licorice root, and the inhibition patterns of Daiokanzoto and rhubarb involve both competitive and noncompetitive inhibition, suggesting that the inhibitory effects of Daiokanzoto are mainly due to rhubarb. Concerning the components of rhubarb, concentration-dependent inhibitory effects were observed for (−)-catechin gallate, (−)-epicatechin gallate, and (−)-epigallocatechin gallate. In conclusion, rhubarb may cause changes in the drug dispositions of P-gp substrates through the inhibition of P-gp. It appears that attention should be given to the interactions between these drugs and Kampo medicines containing rhubarb as an herbal ingredient.

scholarly journals Gastrointestial absorption of pimozide is enhanced by inhibition of P-glycoprotein

2020 ◽  
Author(s):  
Hiroki Morishita ◽  
Kozue Okawa ◽  
Misaki Ishii ◽  
Kenta Mizoi ◽  
Hiroshi Arakawa ◽  
...  
Keyword(s):  
Order Rate Constant ◽  
Glycoprotein P ◽  
Cell Monolayers ◽  
Atpase Assay ◽  
P Glycoprotein ◽  
Efflux Ratio ◽  
Life Threatening ◽  
Antidepressant Combination

AbstractFollowing the death due to cardiac arrest of a patient taking pimozide, sertraline and aripiprazole antipsychotic/antidepressant combination therapy, a role of drug-drug interaction was suggested. Here, we investigated P-glycoprotein (P-gp)-mediated interaction among the three drugs using in vitro methods. Sertraline or aripiprazole significantly increased the permeability of pimozide in Caco-2 cell monolayers. ATPase assay indicated that pimozide is a P-gp substrate, and might act as a P-gp inhibitor at higher concentrations. The values of the kinetic parameters of carrier-mediated efflux, calculated from the concentration dependence of pimozide efflux from LLC-GA5-COL150 cells expressing human P-gp, were as follows: maximum transport rate (Jmax) = 84.9 ± 8.9 pmol/min/mg protein, half-saturation concentration (Kt) = 10.6 ± 4.7 μM, first-order rate constant (kd) = 0.67 ± 0.14 pmol/min/mg protein. Further, the efflux ratio of pimozide in LLC-GA5-COL150 cells was significantly decreased in the presence of sertraline or aripiprazole. These results indicate that pimozide is a substrate of P-gp, and its efflux is inhibited by sertraline and aripiprazole. Thus, P-gp inhibition by sertraline and/or aripiprazole may alter the gastrointestinal permeability of co-administered pimozide, resulting in an increased blood concentration of pimozide, which may increase the likelihood of pimozide’s known life-threatening side effect of QT prolongation.

scholarly journals P-Glycoprotein and Breast Cancer Resistance Protein Restrict Apical-to-Basolateral Permeability of Human Brain Endothelium to Amyloid-β

2009 ◽  
Vol 29 (6) ◽  
pp. 1079-1083 ◽  
Author(s):  
Leon M Tai ◽  
A Jane Loughlin ◽  
David K Male ◽  
Ignacio A Romero
Keyword(s):  
Breast Cancer ◽  
Human Brain ◽  
Breast Cancer Resistance Protein ◽  
Amyloid Β ◽  
Cancer Resistance ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Resistance Protein ◽  
The Brain

The clearance of amyloid beta (Aβ) from the brain represents a novel therapeutic target for Alzheimer's disease. Conflicting data exist regarding the contribution of adenosine triphosphatebinding cassette transporters to the clearance of Aβ through the blood-brain barrier. Therefore, we investigated whether Aβ could be a substrate for P-glycoprotein (P-gp) and/or for breast cancer resistance protein (BCRP) using a human brain endothelial cell line, hCMEC/D3. Inhibition of P-gp and BCRP increased apical-to-basolateral, but not basolateral-to-apical, permeability of hCMEC/D3 cells to 125l Aβ 1–40. Our in vitro data suggest that P-gp and BCRP might act to prevent the blood-borne Aβ 1–40 from entering the brain.

scholarly journals Upregulations of Clcn3 and P-Gp Provoked by Lens Osmotic Expansion in Rat Galactosemic Cataract

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Lixia Ji ◽  
Lixia Cheng ◽  
Zhihong Yang
Keyword(s):  
Osmotic Stress ◽  
Early Stage ◽  
Lens Epithelial Cells ◽  
Anterior Capsule ◽  
Glycoprotein P ◽  
Protein Levels ◽  
P Glycoprotein ◽  
Sugar Cataract

Objective.Lens osmotic expansion, provoked by overactivated aldose reductase (AR), is the most essential event of sugar cataract. Chloride channel 3 (Clcn3) is a volume-sensitive channel, mainly participating in the regulation of cell fundamental volume, and P-glycoprotein (P-gp) acts as its modulator. We aim to study whether P-gp and Clcn3 are involved in lens osmotic expansion of galactosemic cataract.Methods and Results.In vitro, lens epithelial cells (LECs) were primarily cultured in gradient galactose medium (10–60 mM), more and more vacuoles appeared in LEC cytoplasm, and mRNA and protein levels of AR, P-gp, and Clcn3 were synchronously upregulated along with the increase of galactose concentration. In vivo, we focused on the early stage of rat galactosemic cataract, amount of vacuoles arose from equatorial area and scattered to the whole anterior capsule of lenses from the 3rd day to the 9th day, and mRNA and protein levels of P-gp and Clcn3 reached the peak around the 9th or 12th day.Conclusion. Galactosemia caused the osmotic stress in lenses; it also markedly leads to the upregulations of AR, P-gp, and Clcn3 in LECs, together resulting in obvious osmotic expansion in vitro and in vivo.

scholarly journals Immuno-oncology agent IPI-549 is a modulator of P-glycoprotein (P-gp, MDR1, ABCB1)-mediated multidrug resistance (MDR) in cancer: In vitro and in vivo

2019 ◽  
Vol 442 ◽  
pp. 91-103 ◽  
Author(s):  
Albert A. De Vera ◽  
Pranav Gupta ◽  
Zining Lei ◽  
Dan Liao ◽  
Silpa Narayanan ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Glycoprotein P ◽  
P Glycoprotein

scholarly journals Green tea phytocompounds targets Lansterol 14-α demethylase against ergosterol biosynthesis in Candida glabrata

2021 ◽  
Vol 12 (3) ◽  
pp. 1793-1797
Author(s):  
Priyanka Sirari ◽  
Jigisha Anand ◽  
Devvret ◽  
Ashish Thapliyal ◽  
Nishant Rai
Keyword(s):  
Green Tea ◽  
Candida Glabrata ◽  
Scientific Evidence ◽  
Epigallocatechin Gallate ◽  
Ergosterol Biosynthesis ◽  
Epicatechin Gallate ◽  
P450 Monooxygenase ◽  
Antifungal Potential ◽  
Inhibitory Potential

Green tea is credited as one of the world’s healthiest drinks with enriched antioxidants. It is known for its multi-beneficial health benefits against diabetes, blood pressure, hypertension, gastro-intestinal upset and is bestowed with significant antimicrobial potential. There are previous scientific evidence highlighting the antifungal potential of green tea and has identified it as a potential inhibitor of non-albicans Candida species. Lansterol 14-α demethylase (Erg 11) or CYP51 protein belongs to the cytochrome P450 monooxygenase (CYP) superfamily. Erg 11 is involved in ergosterol biosynthesis and has a significant role in azole drug resistance in Candida glabrata. The present study attempted to identify the inhibitory potential of green tea phytocompounds against inhibition of Erg 11 in Candida glabrata using bioinformatics tool viz., autodock vina software. Out of 15 green tea phytocompounds investigated, the study identified, Rutin (-10.5 kcal) Kaempferitrin (-9.4kcal), Epigallocatechin gallate (-10kcal), Epicatechin gallate (-8.7kcal), and Coumaroylquinic acid (-8.6kcal) acid as the potent phytocompounds which showed significant molecular interaction with Erg 11 in Candida glabrata. In attribution to the constant emergence of azole-resistant isolates, this preliminary analysis therefore, indicated the potential of green tea phytocompounds against inhibition of non-albicans Candida specific candidiasis. However, further, in vitro antimicrobial efficacy of these phytocompounds, the dose regime, drug likeliness, and cytotoxic analysis are required to be investigated and validated.

scholarly journals Transport of Alzheimer’s associated amyloid-β catalyzed by P-glycoprotein

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250371
Author(s):  
James W. McCormick ◽  
Lauren Ammerman ◽  
Gang Chen ◽  
Pia D. Vogel ◽  
John G. Wise
Keyword(s):  
Cell Culture ◽  
Atp Hydrolysis ◽  
Amyloid Β ◽  
Md Simulations ◽  
Membrane Transporter ◽  
Biochemical Activity ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Hydrolysis Activity

P-glycoprotein (P-gp) is a critical membrane transporter in the blood brain barrier (BBB) and is implicated in Alzheimer’s disease (AD). However, previous studies on the ability of P-gp to directly transport the Alzheimer’s associated amyloid-β (Aβ) protein have produced contradictory results. Here we use molecular dynamics (MD) simulations, transport substrate accumulation studies in cell culture, and biochemical activity assays to show that P-gp actively transports Aβ. We observed transport of Aβ40 and Aβ42 monomers by P-gp in explicit MD simulations of a putative catalytic cycle. In in vitro assays with P-gp overexpressing cells, we observed enhanced accumulation of fluorescently labeled Aβ42 in the presence of Tariquidar, a potent P-gp inhibitor. We also showed that Aβ42 stimulated the ATP hydrolysis activity of isolated P-gp in nanodiscs. Our findings expand the substrate profile of P-gp, and suggest that P-gp may contribute to the onset and progression of AD.

scholarly journals Pharmacokinetic Alteration of Paclitaxel by Ferulic Acid Derivative

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 593 ◽  
Author(s):  
Jaeok Lee ◽  
Song Wha Chae ◽  
LianJi Ma ◽  
So Yeon Lim ◽  
Sarah Alnajjar ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Ferulic Acid ◽  
Acid Derivative ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Substrate Drug

P-glycoprotein (P-gp) is known to be involved in multidrug resistance (MDR) and modulation of pharmacokinetic (PK) profiles of substrate drugs. Here, we studied the effects of synthesized ferulic acid (FA) derivatives on P-gp function in vitro and examined PK alteration of paclitaxel (PTX), a well-known P-gp substrate drug by the derivative. Compound 5c, the FA derivative chosen as a significant P-gp inhibitor among eight FA candidates by in vitro results, increased PTX AUCinf as much as twofold versus the control by reducing PTX elimination in rats. These results suggest that FA derivative can increase PTX bioavailability by inhibiting P-gp existing in eliminating organs.

scholarly journals Bioactive Compounds and Antioxidant Activity of Mango Peel Liqueurs (Mangifera indica L.) Produced by Different Methods of Maceration

Antioxidants ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 102 ◽  
Author(s):  
Emanuela Monteiro Coelho ◽  
Marcelo Eduardo Alves Olinda de Souza ◽  
Luiz Claudio Corrêa ◽  
Arão Cardoso Viana ◽  
Luciana Cavalcanti de Azevêdo ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Bioactive Compounds ◽  
High Performance ◽  
Mangifera Indica ◽  
Epigallocatechin Gallate ◽  
Reversed Phase ◽  
Epicatechin Gallate ◽  
Bioactive Content ◽  
Mango Peels

The present work had the objective of producing liqueurs from mango peels (varieties “Haden” and “Tommy Atkins”) by processes of alcoholic maceration and maceration with pectinase, as well as to evaluate bioactive compounds by reversed-phase high-performance liquid chromatography coupled to diode array detection and fluorescence-detection (RP-HPLC/DAD/FD) and in vitro antioxidant activity (AOX), for by-product potential reuse. Alcoholic maceration in wine ethanol (65% v/v) produced liqueurs with higher phytochemical and AOX content. Maceration with pectinase resulted in liqueurs with higher quercetin-3-O-glucopyranoside content. In relation to mango varieties, Haden liqueurs presented higher bioactive content than Tommy Atkins liqueurs. The liqueurs presented high antioxidant activity. The main bioactive compounds found were flavanols (epicatechin-gallate, epigallocatechin-gallate), flavonols (quercetin-3-O-glucopyranoside and rutin), and phenolic acids (gallic acid, o-coumaric acid, and syringic acid). The present study showed that the production of liqueur enabled the recovering of an important part of the bioactive content of mango peels, suggesting an alternative for the recovery of antioxidant substances from this by-product.

Reversal of chemoresistance in malignant gliomas by calcium antagonists: correlation with the expression of multidrug-resistant p-glycoprotein

1994 ◽  
Vol 81 (4) ◽  
pp. 587-594 ◽  
Author(s):  
Jurgen Carl Walther Kiwit ◽  
Anja Hertel ◽  
Alexander E. Matuschek
Keyword(s):  
Calcium Antagonists ◽  
Malignant Gliomas ◽  
Multidrug Resistant ◽  
Chemotherapeutic Agents ◽  
Positive Staining ◽  
Glycoprotein P ◽  
Content Type ◽  
P Glycoprotein ◽  
Multiple Drugs

✓ Resistance to multiple drugs is often observed in malignant gliomas. The authors used a microtiter tetrazolium test to analyze primary in vitro chemoresistance and chemosensitivity of 15 early cultures of human malignant glioma exposed to 50 µg/ml (1,4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), 50 µg/ml cisplatin, 1 µg/ml vincristine, or combinations of these chemotherapeutic agents. Primary chemoresistance was observed in 87% of tumors for ACNU, in 87% for cisplatin, and in 83% for vincristine. All tumors were examined for expression of multidrug-resistant p-glycoprotein, a transport protein of 170,000 D, by means of immunohistochemical staining with the JSB-1 antibody on paraffinized tumor sections. Eight of 15 specimens (53%) showed positive staining for the monoclonal antibody. Primary chemoresistance was overcome by addition of the calcium antagonists verapamil or nimodipine to the cultures if the original tumor expressed p-glycoprotein (p < 0.01 for verapamil, p < 0.05 for nimodipine). In tumors not expressing p-glycoprotein, addition of calcium antagonists to the cell cultures did not influence primary chemoresistance. It is concluded from these data that addition of calcium antagonists to the adjuvant chemotherapy of malignant gliomas might overcome primary chemoresistance in tumors expressing the multidrugresistant phenotype.

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