Objectives: Atractylodin and β-eudesmol are the two active
constituents of Atractylodes lancea (Thunb.) D.C. (AL), which has been
demonstrated in a series of in vitro and in vivo studies for its potential
activities against cholangiocarcinoma. The objective of the study was to investigate
membrane permeability properties and effects on the efflux transporter
P-glycoprotein (P-gp) using the Caco-2 cell line.
Methods: The Caco-2 cell monolayer's integrity was evaluated by
measuring trans-epithelial electrical resistance (TEER) and permeation (Papp)
of Lucifer yellow across the cell monolayer. The effects of atractylodin and
β-eudesmol on P-gp were determined by measuring interference with the transport
of the P-gp transport (Rhodamine 123: R123), and their modulatory effects on
MDR-1 mRNA were detected using real-time polymerase chain reaction (RT-PCR).
Key Findings: The Papp values of atractylodin (50-200
µM) from apical to basolateral (A-B) and basolateral to apical (B-A) directions
were 0.02-0.03×10-6 and 0.06-0.08×10-6 cm/sec, respectively, with the efflux
ratios ranging from 2.5 to 2.9. The corresponding Papp values of
β-eudesmol (50-200 µM) were 0.87-0.91×10-6 and 2.97-3.95×10-6 cm/sec,
respectively, with the efflux ratios ranging from 3.24 to 4.63. Neither
compounds were not inhibitors of P-gp and did not affect P-gp-mediated R123
transport across the Caco-2 cell monolayer. β-Eudesmol did not affect the
function of P-glycoprotein and MDR-1 mRNA expression, while exposure to
atractylodin at high concentration (320 µM) for 48 h induced P-gp at both gene
and function levels.
Conclusions: Atractylodin and β-eudesmol exhibit low permeability
across the Caco-2 cell monolayer in both directions, which is attributed to the
efflux transport of both compounds into the cells. Inadequate concentrations of
both compounds in the target cells may limit the clinical use of AL in patients
with cholangiocarcinoma.
Author(s) Details
Artitaya
Thiengsusuk
Graduate Studies, Chulabhorn International College of Medicine,
Thammasat University, Pathum Thani 12120, Thailand.
Wiriyaporn
Sumsakul
Thailand Institute of Scientific and Technological Research,
Pathum Thani 12120, Thailand.
Kesara
Na-Bangchang
Graduate Studies, Chulabhorn International College of Medicine,
Thammasat University, Pathum Thani 12120, Thailand, Center of Excellence in
Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat
University, Pathum Thani 12120, Thailand and Drug Discovery and Development
Center, Office of Advanced Science and Technology, Thammasat University, Pathum
Thani 12120, Thailand.
Please see the book here:- https://doi.org/10.9734/bpi/mbrao/v4/5795
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