Effects of atractylodin and β-Eudesmol on P-glycoprotein and Caco-2 cells permeability
Background: Atractylodin and β-eudesmol are the major constituents of Atractylodes lancea (Thunb.) D.C. (AL) which have been demonstrated potential activities against cholangiocarcinoma in a series of in vitro and in vivo studies. Purpose: The study investigated their membrane permeability propertie...
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Elsevier
2025-02-01
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| Series: | Phytomedicine Plus |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667031324000836 |
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| author | Artitaya Thiengsusuk Wiriyaporn Sumsakul Kesara Na–Bangchang |
| author_facet | Artitaya Thiengsusuk Wiriyaporn Sumsakul Kesara Na–Bangchang |
| author_sort | Artitaya Thiengsusuk |
| collection | DOAJ |
| description | Background: Atractylodin and β-eudesmol are the major constituents of Atractylodes lancea (Thunb.) D.C. (AL) which have been demonstrated potential activities against cholangiocarcinoma in a series of in vitro and in vivo studies. Purpose: The study investigated their membrane permeability properties and effects on the efflux transporter P-glycoprotein (P-gp) using a Caco-2 cell monolayer. Methods: The transport and modulatory effects of both compounds on the expression of MDR-1 mRNA and protein, including P-gp function were investigated using the Caco-2 cells, RT-PCR, western blot analysis, and Rhodamine 123 (R123) assay, respectively. Results: The efflux ratio of atractylodin and β-eudesmol (50–200 µM) was higher than 2, indicating the predominant efflux transport of both compounds compared with the influx transport. However, neither of the compounds were P-gp inhibitors nor modulators of the expression of MDR-1 mRNA, and P-gp function. Only a slight inhibitory effect was observed with atractylodin exposure at 160 µM for 24 hrs. Conclusion: The low permeability of both compounds across the Caco-2 cell monolayer in both directions may lead to inadequate concentrations in the target cells, which may limit the clinical use of AL in cholangiocarcinoma treatment. Concurrent administration of both compounds and substrates of P-gp is not a clinical concern since neither compound is an inhibitor of P-gp in Caco-2 monolayers. |
| format | Article |
| id | doaj-art-79dbda225839423c811c4269ffb9302e |
| institution | Kabale University |
| issn | 2667-0313 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Phytomedicine Plus |
| spelling | doaj-art-79dbda225839423c811c4269ffb9302e2025-02-10T04:35:03ZengElsevierPhytomedicine Plus2667-03132025-02-0151100608Effects of atractylodin and β-Eudesmol on P-glycoprotein and Caco-2 cells permeabilityArtitaya Thiengsusuk0Wiriyaporn Sumsakul1Kesara Na–Bangchang2Graduate Studies, Chulabhorn International College of Medicine, Thammasat University, Pathumthani 12120, ThailandThailand Institute of Scientific and Technological Research, Pathumthani 12120, ThailandGraduate Studies, Chulabhorn International College of Medicine, Thammasat University, Pathumthani 12120, Thailand; Drug Discovery and Development Center, Office of Advanced Science and Technology, Thammasat University, Pathumthani 12120, Thailand; Corresponding author.Background: Atractylodin and β-eudesmol are the major constituents of Atractylodes lancea (Thunb.) D.C. (AL) which have been demonstrated potential activities against cholangiocarcinoma in a series of in vitro and in vivo studies. Purpose: The study investigated their membrane permeability properties and effects on the efflux transporter P-glycoprotein (P-gp) using a Caco-2 cell monolayer. Methods: The transport and modulatory effects of both compounds on the expression of MDR-1 mRNA and protein, including P-gp function were investigated using the Caco-2 cells, RT-PCR, western blot analysis, and Rhodamine 123 (R123) assay, respectively. Results: The efflux ratio of atractylodin and β-eudesmol (50–200 µM) was higher than 2, indicating the predominant efflux transport of both compounds compared with the influx transport. However, neither of the compounds were P-gp inhibitors nor modulators of the expression of MDR-1 mRNA, and P-gp function. Only a slight inhibitory effect was observed with atractylodin exposure at 160 µM for 24 hrs. Conclusion: The low permeability of both compounds across the Caco-2 cell monolayer in both directions may lead to inadequate concentrations in the target cells, which may limit the clinical use of AL in cholangiocarcinoma treatment. Concurrent administration of both compounds and substrates of P-gp is not a clinical concern since neither compound is an inhibitor of P-gp in Caco-2 monolayers.http://www.sciencedirect.com/science/article/pii/S2667031324000836AtractylodinΒ-eudesmolCaco-2 cellsP-glycoproteinMembrane permeability |
| spellingShingle | Artitaya Thiengsusuk Wiriyaporn Sumsakul Kesara Na–Bangchang Effects of atractylodin and β-Eudesmol on P-glycoprotein and Caco-2 cells permeability Phytomedicine Plus Atractylodin Β-eudesmol Caco-2 cells P-glycoprotein Membrane permeability |
| title | Effects of atractylodin and β-Eudesmol on P-glycoprotein and Caco-2 cells permeability |
| title_full | Effects of atractylodin and β-Eudesmol on P-glycoprotein and Caco-2 cells permeability |
| title_fullStr | Effects of atractylodin and β-Eudesmol on P-glycoprotein and Caco-2 cells permeability |
| title_full_unstemmed | Effects of atractylodin and β-Eudesmol on P-glycoprotein and Caco-2 cells permeability |
| title_short | Effects of atractylodin and β-Eudesmol on P-glycoprotein and Caco-2 cells permeability |
| title_sort | effects of atractylodin and β eudesmol on p glycoprotein and caco 2 cells permeability |
| topic | Atractylodin Β-eudesmol Caco-2 cells P-glycoprotein Membrane permeability |
| url | http://www.sciencedirect.com/science/article/pii/S2667031324000836 |
| work_keys_str_mv | AT artitayathiengsusuk effectsofatractylodinandbeudesmolonpglycoproteinandcaco2cellspermeability AT wiriyapornsumsakul effectsofatractylodinandbeudesmolonpglycoproteinandcaco2cellspermeability AT kesaranabangchang effectsofatractylodinandbeudesmolonpglycoproteinandcaco2cellspermeability |