Publication: β-eudesmol but not atractylodin exerts an inhibitory effect on CFTR-mediated chloride transport in human intestinal epithelial cells
Issued Date
2021-10-01
Resource Type
ISSN
19506007
07533322
07533322
Other identifier(s)
2-s2.0-85113682872
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biomedicine and Pharmacotherapy. Vol.142, (2021)
Suggested Citation
Phuntila Tharabenjasin, Ronaldo P. Ferraris, Kiattawee Choowongkomon, Pawin Pongkorpsakol, Nichakorn Worakajit, Sutthipong Sawasvirojwong, Noel Pabalan, Kesara Na-Bangchang, Chatchai Muanprasat β-eudesmol but not atractylodin exerts an inhibitory effect on CFTR-mediated chloride transport in human intestinal epithelial cells. Biomedicine and Pharmacotherapy. Vol.142, (2021). doi:10.1016/j.biopha.2021.112030 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/78944
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
β-eudesmol but not atractylodin exerts an inhibitory effect on CFTR-mediated chloride transport in human intestinal epithelial cells
Abstract
Oriental herbal medicine with the two bioactive constituents, β-eudesmol (BE) and atractylodin (AT), has been used as a remedy for gastrointestinal disorders. There was no scientific evidence reporting their antidiarrheal effect and underpinning mechanisms. Therefore, we aimed to investigate the anti-secretory activity of these two compounds in vitro. The inhibitory effect of BE and AT on cAMP-induced Cl- secretion was evaluated by Ussing chamber in human intestinal epithelial (T84) cells. Short-circuit current (ISC) and apical Cl- current (ICl-) were measured after adding indirect and direct cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activator. MTT assay was used to determine cellular cytotoxicity. Protein-ligand interaction was investigated by in silico molecular docking analysis. BE, but not AT concentration-dependently (IC50 of ~1.05 µM) reduced cAMP-mediated, CFTRinh-172 inhibitable Cl− secretion as determined by transepithelial ISC across a monolayer of T84 cells. Potency of CFTR-mediated ICl- inhibition by BE did not change with the use of different CFTR activators suggesting a direct blockage of the channel active site(s). Pretreatment with BE completely prevented cAMP-induced ICl-. Furthermore, BE at concentrations up to 200 µM (24 h) had no effect on T84 cell viability. In silico studies indicated that BE could best dock onto dephosphorylated structure of CFTR at ATP-binding pockets in nucleotide-binding domain (NBD) 2 region. These findings provide the first evidence for the anti-secretory effect of BE involving inhibition of CFTR function. BE represents a promising candidate for the therapeutic or prophylactic intervention of diarrhea resulted from intestinal hypersecretion of Cl-