Transport and Interactions of Co-incubated Bi-functional Flavonoids through Inhibiting the Function of P-Glycoprotein (P-gp) Using KB/Multidrug-Resistant (MDR) Cells and Rat Everted Gut Sacs
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Transport and Interactions of Co-incubated Bi-functional Flavonoids through Inhibiting the Function of P-Glycoprotein (P-gp) Using KB/Multidrug-Resistant (MDR) Cells and Rat Everted Gut Sacs. / Fang, Yajing; Cao, Weiwei; Xia, Mengmeng; Pan, Siyi; Xu, Xiaoyun.
In: Journal of Agricultural and Food Chemistry, Vol. 70, No. 6, 2022, p. 1923-1933.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Transport and Interactions of Co-incubated Bi-functional Flavonoids through Inhibiting the Function of P-Glycoprotein (P-gp) Using KB/Multidrug-Resistant (MDR) Cells and Rat Everted Gut Sacs
AU - Fang, Yajing
AU - Cao, Weiwei
AU - Xia, Mengmeng
AU - Pan, Siyi
AU - Xu, Xiaoyun
N1 - Funding Information: This work was supported by the National Natural Science Foundation of China (31471625).
PY - 2022
Y1 - 2022
N2 - This study aims to evaluate the interaction of flavonoid-flavonoid by inhibiting the function of P-glycoprotein (P-gp). The cellular uptake of seven substrates and eleven co-incubated inhibitors was measured in KB/MDR cells. The effect of galangin or morin on the absorption of silibinin or wogonin was carried out in the rat everted gut sacs. Docking was performed to evaluate the interactions between inhibitors and P-gp. Most substrates were greatly enhanced by at least five co-incubated inhibitors. Conversely, the increased uptake of substrates coincided with a decrease or without affecting the uptake of inhibitors, implying a competitive/non-competitive inhibition on P-gp. The enhancement effect by galangin or morin on the transport of silibinin or wogonin was verified in everted gut sacs. Docking explained the inhibition of flavonoids on P-gp by competitively binding to the ATP site. These results provide a strategy for increasing the absorption of flavonoids by co-administration.
AB - This study aims to evaluate the interaction of flavonoid-flavonoid by inhibiting the function of P-glycoprotein (P-gp). The cellular uptake of seven substrates and eleven co-incubated inhibitors was measured in KB/MDR cells. The effect of galangin or morin on the absorption of silibinin or wogonin was carried out in the rat everted gut sacs. Docking was performed to evaluate the interactions between inhibitors and P-gp. Most substrates were greatly enhanced by at least five co-incubated inhibitors. Conversely, the increased uptake of substrates coincided with a decrease or without affecting the uptake of inhibitors, implying a competitive/non-competitive inhibition on P-gp. The enhancement effect by galangin or morin on the transport of silibinin or wogonin was verified in everted gut sacs. Docking explained the inhibition of flavonoids on P-gp by competitively binding to the ATP site. These results provide a strategy for increasing the absorption of flavonoids by co-administration.
KW - cellular uptake
KW - co-administration
KW - flavonoid inhibitors
KW - flavonoid substrates
KW - molecular docking
KW - P-glycoprotein
U2 - 10.1021/acs.jafc.1c07694
DO - 10.1021/acs.jafc.1c07694
M3 - Journal article
C2 - 35112564
AN - SCOPUS:85124456503
VL - 70
SP - 1923
EP - 1933
JO - Journal of Agricultural and Food Chemistry
JF - Journal of Agricultural and Food Chemistry
SN - 0021-8561
IS - 6
ER -
ID: 300067285