Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 66, Issue 4, Pages 988-998Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.7b04307
Keywords
allosteric modulation; efflux; P-glycoprotein inhibitor; phytic acid; rhodamine 123
Funding
- National Science Foundation of China [81303304]
- Shanghai Talent Development Fund [201565]
- Shu Guang project - Shanghai Education Development Foundation [15SG39]
- Shu Guang project - Shanghai Municipal Education Commission [15SG39]
- Shanghai Pujiang Program [16PJD044]
- scientific and technological innovation project of traditional Chinese Medicine - Shanghai Health and Family Planning Commission [ZYKC201603008]
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Phytic acid (IP6) is a natural phosphorylated inositol, which is abundantly present in most cereal grains and seeds. This study investigated the effects of IP6 regulation on P-glycoprotein (P-gp) and its potential mechanisms using in situ and in vitro models. The effective permeability of the typical P-gp substrate rhodamine 123 (R123) in colon was significantly increased from (1.69 +/- 0.22) x 10(-5) cm/s in the control group to (3.39 +/- 0.417) x 10(-5) cm/s (p < 0.01) in the 3.5 mM IP6 group. Additionally, IP6 can concentration-dependently decrease the R123 efflux ratio in both Caco-2 and MDCK II-MDR1 cell monolayers and increase intracellular R123 accumulation in Caco-2 cells. Furthermore, IP6 noncompetitively inhibited P-gp by impacting R123 efflux kinetics. The noncompetitive inhibition of P-gp by IP6 was likely due to decreases in P-gp ATPase activity and P-gp molecular conformational changes induced by IP6. In summary, IP6 is a promising P-gp inhibitor candidate.
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