• Phytic Acid Inhibition of P-Glycoprotein

    From ironjustice@21:1/5 to All on Mon Mar 5 20:23:23 2018
    Inhibition of P-Glycoprotein Mediated Efflux in Caco-2 Cells by Phytic Acid Lujia Li†§∇, Qingxue Fu†‡∇, Mengxin Xia†, Lei Xin†, Hongyi Shen†, Guowen Li§, Guang Ji∥, Qianchao Meng⊥, and Yan Xie*†∥
    † Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
    ‡ Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
    § Pharmacy Department, Shanghai TCM-integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
    ∥ Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
    ⊥ Center for Drug Safety Evaluation, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
    J. Agric. Food Chem., 2018, 66 (4), pp 988–998
    DOI: 10.1021/acs.jafc.7b04307
    Publication Date (Web): December 28, 2017
    Copyright © 2017 American Chemical Society
    *Yan Xie. Mailing address: Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China. E-mail: rosexie_1996 at hotmail.com; yxie at shutcm.edu.cn.
    Phone: +86(21)51322440. Fax: +86(21)51322407.
    Cite this:J. Agric. Food Chem. 66, 4, 988-998

    Abstract
    Abstract Image
    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) × 10–5 cm/s in the control group to (3.39 ± 0.417) × 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.

    Keywords: allosteric modulation; efflux; P-glycoprotein inhibitor; phytic acid; rhodamine 123

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