Publication: Activation of AMP-activated protein kinase by a plant-derived dihydroisosteviol in human intestinal epithelial cell
Issued Date
2013-04-01
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ISSN
13475215
09186158
09186158
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2-s2.0-84876917331
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Mahidol University
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SCOPUS
Bibliographic Citation
Biological and Pharmaceutical Bulletin. Vol.36, No.4 (2013), 522-528
Suggested Citation
Chatchai Muanprasat, Lalida Sirianant, Sutthipong Sawasvirojwong, Sureeporn Homvisasevongsa, Apichart Suksamrarn, Varanuj Chatsudthipong Activation of AMP-activated protein kinase by a plant-derived dihydroisosteviol in human intestinal epithelial cell. Biological and Pharmaceutical Bulletin. Vol.36, No.4 (2013), 522-528. doi:10.1248/bpb.b12-00711 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/32743
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Title
Activation of AMP-activated protein kinase by a plant-derived dihydroisosteviol in human intestinal epithelial cell
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Abstract
Our previous study has shown that dihydroisosteviol (DHIS), a derivative of stevioside isolated from Stevia rebaudiana (Bertoni), inhibits cystic fibrosis transmembrane conductance regulator (CFTR)-mediated transepithelial chloride secretion across monolayers of human intestinal epithelial (T84) cells and prevents cholera toxin-induced intestinal fluid secretion in mouse closed loop models. In this study, we aimed to investigate a mechanism by which DHIS inhibits CFTR activity. Apical chloride current measurements in Fisher rat thyroid cells stably transfected with wild-type human CFTR (FRT-CFTR cells) and T84 cells were used to investigate mechanism of CFTR inhibition by DHIS. In addition, effect of DHIS on AMP-activated protein kinase (AMPK) activation was investigated using Western blot analysis. Surprisingly, it was found that DHIS failed to inhibit CFTR-mediated apical chloride current in FRT-CFTR cells. In contrast, DHIS effectively inhibited CFTR-mediated apical chloride current induced by a cell permeable cAMP analog CPT-cAMP and a direct CFTR activator genistein in T84 cell monolayers. Interestingly, this inhibitory effect of DHIS on CFTR was significantly (p<0.05) reduced by pretreatment with compound C, an AMPK inhibitor. AICAR, a known AMPK activator, was able to inhibit CFTR activity in both FRT-CFTR and T84 cells. Western blot analysis showed that DHIS induced AMPK activation in T84 cells, but not in FRT-CFTR cells. Our results indicate that DHIS inhibits CFTR-mediated chloride secretion in T84 cells, in part, by activation of AMPK activity. DHIS therefore represents a novel candidate of AMPK activators. © 2013 The Pharmaceutical Society of Japan.