RGD Reference Report - Dioscin enhances methotrexate absorption by down-regulating MDR1 in vitro and in vivo. - Rat Genome Database

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Dioscin enhances methotrexate absorption by down-regulating MDR1 in vitro and in vivo.

Authors: Wang, L  Wang, C  Peng, J  Liu, Q  Meng, Q  Sun, H  Huo, X  Sun, P  Yang, X  Zhen, Y  Liu, K 
Citation: Wang L, etal., Toxicol Appl Pharmacol. 2014 Jun 1;277(2):146-54. doi: 10.1016/j.taap.2014.03.013. Epub 2014 Mar 26.
RGD ID: 11040929
Pubmed: PMID:24680847   (View Abstract at PubMed)
DOI: DOI:10.1016/j.taap.2014.03.013   (Journal Full-text)

The purpose of this study was to investigate the enhancing effect of dioscin on the absorption of methotrexate (MTX) and clarify the molecular mechanism involved in vivo and in vitro. Dioscin increased MTX chemosensitivity and transepithelial flux in the absorptive direction, significantly inhibiting multidrug resistance 1 (MDR1) mRNA and protein expression and MDR1 promoter and nuclear factor kappa-B (NF-kappaB) activities in Caco-2 cells. Moreover, inhibitor kappaB-alpha (IkappaB-alpha) degradation was inhibited by dioscin. Dioscin enhanced the intracellular concentration of MTX by down-regulating MDR1 expression through a mechanism that involves NF-kappaB signaling pathway inhibition in Caco-2 cells. Dioscin strengthened MTX absorption by inhibiting MDR1 expression in rat intestine. In addition, even though MTX is absorbed into the enterocytes, there was no increase in toxicity observed, and that, in fact, decreased toxicity was seen.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Abcb1aRatresponse to glycoside  IEP dioscinRGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcb1a  (ATP binding cassette subfamily B member 1A)


Additional Information